1268 Unit 10 Pharmacology of the Endocrine System
CONNECTIONS: NURSING PRACTICE APPLICATION (continued)
Implementation
Interventions and (Rationales) Patient-Centered Care
• Monitor Pap tests, HPV screening, and breast examinations as • Teach the patient how to perform breast self-examinations, noting that
ordered. (Pap tests and breast examinations, including mammography monthly examinations may not be recommended by the healthcare
as appropriate, will monitor for the development of breast tumors or of provider except for women at high risk for breast cancer. For women
cervical cancer.) over age 40, advise the patient on the need for follow-up
mammography per healthcare provider recommendations.
• Advise the patient on the need for routine age-appropriate
gynecologic examinations to ensure continued health. Frequency may
be decreased after age 65 after consultation with the healthcare
provider.
• Monitor for the occurrence of any breakthrough bleeding. Report any • Teach the patient that slight spotting may occur midcycle while on
continuous, unusual, or heavy bleeding. (Small amounts of spotting estrogens but to report any unusual changes in the amount or if the
may occur, especially with low-dose hormone therapy, at midcycle. bleeding continues.
Any continuous, unusual, or heavy bleeding may indicate adverse
effects or disease and should be reported because an increased
risk of endometrial cancer has been noted with estrogen use.)
• Monitor hepatic function tests and symptoms of liver dysfunction, • Instruct the patient to return periodically for laboratory tests.
lipid profile studies, and thyroid levels periodically. (Estrogens are • Teach the patient to report any symptoms of abdominal or right upper
associated with increased risk of gallbladder disease and a rare risk
of hepatotoxicity. Diverse Patients: Because estrogens metabolize quadrant discomfort or pain, yellowing of the skin or sclera, fatigue,
through the CYP450 system pathways, monitor ethnically diverse anorexia, darkened urine, or clay-colored stools immediately.
patients to ensure optimal therapeutic effects and to minimize
adverse effects.)
• Monitor concurrent drug therapy and any new prescriptions received. • Teach the patient to advise all healthcare providers of the use of
(Many drugs decrease or alter the effectiveness of estrogens including estrogens before beginning any new prescription.
drugs in the penicillin, barbiturate, antiseizure, antidepressant, and
benzodiazepine classifications. Check for drug interactions that may
affect hormone effectiveness before any new prescription is started.)
Patient understanding of drug therapy: • The patient should be able to state the reason for the drug, appropriate
• Use opportunities during administration of medications and during dose and scheduling, what adverse effects to observe for, and when to
report them.
assessments to discuss the rationale for drug therapy, desired
therapeutic outcomes, commonly observed adverse effects, parameters
for when to call the healthcare provider, and any necessary monitoring
or precautions. (Using time during nursing care helps to optimize and
reinforce key teaching areas.)
Patient self-administration of drug therapy: • Teach the patient to take the drug following appropriate guidelines:
• When administering the medication, instruct the patient in proper self- • Oral drugs should be taken at the same time each day to help
remember the dose. Follow instructions if a dose is missed.
administration of the drug, e.g., consistently at the same time each day • Transdermal patches (e.g., Climara) are changed weekly or every
to help remember the dose, followed by teach-back. (Utilizing time other week per the healthcare provider’s directions.
during nurse administration of these drugs helps reinforce teaching.) • Apply topical gels or creams only to the area to be treated.
Do not wear tampons after intravaginal application.
Whereas the function of estrogen is to cause prolifera- PharmFACT
tion of the endometrium, progesterone limits and stabi-
lizes endometrial growth. Progestins are preferred drugs Dysfunctional uterine bleeding most commonly occurs at the
for treating many uterine abnormalities. They are also a extreme ages of the reproductive years. The most severe
component of HRT and are used as contraceptives (see cases occur in adolescents during the first 2 years after the
Chapter 70). onset of menstruation. Abnormal bleeding also occurs in
50% of perimenopausal women (Estephan, 2016).
The primary noncontraception indication for proges-
tins is dysfunctional uterine bleeding, a condition in Ninety percent of dysfunctional uterine bleeding cases
which hemorrhage occurs on a noncyclic basis or in abnor- result from anovulation. Possible causes of uterine bleed-
mal amounts. Dysfunctional uterine bleeding is common ing include early abortion, pelvic neoplasms, thyroid disor-
in adolescents and menopausal women and is often associ- ders, pregnancy, and infection. Types of dysfunctional
ated with anovulatory menstrual cycles. Anovulatory uterine bleeding include the following:
cycles are those that occur without ovulation. Dysfunc-
tional uterine bleeding is the health problem most fre- • Amenorrhea. Absence of menstruation
quently reported by women and a common reason for a • Endometriosis. Abnormal location of endometrial
hysterectomy.
tissues
Chapter 69 Estrogens, Progestins, and Drugs Modifying Uterine Function 1269
• Oligomenorrhea. Infrequent menstruation given by the subcutaneous route (Depo-Provera) as a con-
• Menorrhagia. Prolonged or excessive menstruation traceptive. The use of medroxyprogesterone in contracep-
tion is presented in Chapter 70. The drug has been used
occurring at regular intervals off-label to treat symptoms of menopause.
• Breakthrough (intermenstrual) bleeding. Hemor-
Mechanism of Action: This drug is a synthetic deriva-
rhage between regular menstrual periods tive of progesterone with prolonged, variable duration of
• Premenstrual syndrome (PMS). Symptoms devel- action and androgenic and antiestrogenic activity. The drug
inhibits GnRH, thus preventing the LH surge and ovulation.
oped during the luteal phase
• Postmenopausal bleeding. Hemorrhage following Pharmacokinetics:
menopause Route(s) PO, IM, subcutaneous, IV
• Endometrial carcinoma. Cancer of the endometrium.
Absorption Readily absorbed from the GI
Dysfunctional uterine bleeding is often due to a hor-
monal imbalance between estrogen and progesterone. tract or IM
Although estrogen increases the thickness of the endome-
trium, bleeding occurs sporadically unless it is balanced by Distribution Crosses the placenta; secreted in
adequate progesterone secretion. Administration of a pro-
gestin in a regimen starting 5 days after the onset of menses breast milk; 90% bound to protein
and continuing for the next 20 days can sometimes help to
reestablish a normal, monthly cyclic pattern. Oral contra- Primary metabolism Hepatic
ceptives may also be prescribed for this disorder.
Primary excretion Feces
In patients experiencing heavy bleeding, high doses of
conjugated estrogens may be administered for 3 weeks Onset of action PO: 30–60 min; IM: 15–30 min
prior to adding medroxyprogesterone for the last 10 days
of therapy. Treatment with nonsteroidal anti-inflammatory Duration of action Half-life: 30 days (PO);
drugs (NSAIDs) helps to ease painful menstrual flow. If
aggressive hormonal therapy fails to stop the heavy bleed- 50 days (IM)
ing, dilation and curettage (D&C) may be necessary.
Adverse Effects: The most common adverse effects of
Progestins are occasionally prescribed for the treat- medroxyprogesterone are breast tenderness, breakthrough
ment of metastatic endometrial carcinoma. In these cases, bleeding, and other menstrual irregularities. Weight gain,
they are used for palliation, in combination with other anti- depression, hypertension (HTN), nausea, vomiting, fluid
neoplastics. Selected progestins and their dosages are retention, and vaginal candidiasis may also occur. Black
shown in Table 69.1. Box Warning: Progestins combined with conjugated estro-
gens may increase the risk of stroke, DVT, MI, pulmonary
PROTOTYPE DRUG Medroxyprogesterone emboli, and invasive breast cancer. Women age 65 or older
(Depo-Provera, Depo-SubQ- have an increased risk of dementia when treated with pro-
Provera, Provera) gestins. Women receiving injectable medroxyprogesterone
are at significant risk for loss of bone mineral density.
Classification Therapeutic: Hormone, drug for dysfun
ctional uterine bleeding Contraindications/Precautions: Patients with a
history of thromboembolic disorders, or who are preg-
Pharmacologic: Progestin nant, should not take progestins. Doses should be reduced
in patients with hepatic impairment. Patients with pre-
Therapeutic Effects and Uses: Approved in 1959, existing breast, uterine, or vaginal cancer should not
medroxyprogesterone is a synthetic progestin with a receive medroxyprogesterone unless it is for palliation
prolonged duration of action. Like progesterone, the pri- of advanced cancer. The drug should be used cautiously
mary target tissue for medroxyprogesterone is the uterine in patients with a history of psychic depression, and the
endometrium. It antagonizes the effects of estrogen on the drug should be discontinued at the first sign of recurring
uterus, thus restoring normal hormonal balance. It also depression. The drug is absolutely contraindicated in
inhibits the midcycle LH surge, which prevents ovulation, patients with known or suspected pregnancy (category X)
and causes a thick cervical mucus plug that is resistant to or in those with undiagnosed vaginal bleeding.
the passage of sperm.
Drug Interactions: Serum levels of medroxypro-
Medroxyprogesterone is given PO (Provera) to treat gesterone are decreased by barbiturates, carbamazepine,
dysfunctional uterine bleeding or secondary amenorrhea. rifabutin, rifampin, and topiramate. Azole antifungals, car-
It is administered IM (Depo-SubQ-Provera) at high doses bamazepine, nicardipine, and protease inhibitors such as
for the palliative treatment of inoperable metastatic endo- ritonavir will increase the effects of medroxyprogesterone.
metrial or renal cell carcinoma. At low doses, the drug is Herbal/Food: St. John’s wort may cause intermenstrual
bleeding and loss of efficacy. Grapefruit may increase the
effects of medroxyprogesterone.
1270 Unit 10 Pharmacology of the Endocrine System
Pregnancy: Category X. is used to treat infertile women with progesterone defi-
ciency as part of an assisted reproductive technology sys-
Treatment of Overdose: Overdose is treated tem. The vaginal formulations may also be used as
symptomatically. progesterone supplements to support embryo implanta-
tion and early pregnancy. When used intravaginally, the
Nursing Responsibilities: Key nursing implications drug may be absorbed and cause systemic adverse effects
for patients receiving medroxyprogesterone are included such as breast tenderness, bloating, drowsiness, head-
in the Nursing Practice Application for Patients Receiving aches, irritability, and mood swings.
Pharmacotherapy with Progestin.
Oral capsules (Prometrium) are approved to treat sec-
Drugs Similar to Medroxyprogesterone ondary amenorrhea and may be used off-label to ease
(Depo-Provera, Depo-SubQ-Provera, Provera) symptoms of PMS. Prometrium is also indicated for the
prevention of endometrial hyperplasia in postmenopausal
Progestins used as contraceptives include desogestrel, dieno- women who are receiving conjugated estrogens.
gest, levonorgestrel, norethindrone, and norgestrel. These are
presented in Chapter 70. Another progestin is progesterone. Progesterone IM injections are indicated for amenor-
rhea and to stop abnormal uterine bleeding. Adverse effects
Progesterone (Crinone, Endometrin, Prochieve, Prome- and contraindications are the same as those for medroxypro-
trium): Approved in 1978, progesterone is available in a gesterone. The PO and IM progesterone formulations carry
variety of formulations. As a vaginal suppository (Endo- the same black box warnings as medroxyprogesterone and
metrin) or vaginal gel (Crinone, Prochieve), progesterone are pregnancy category X. The vaginal gel is category B.
CONNECTIONS: NURSING PRACTICE APPLICATION
Patients Receiving Pharmacotherapy with Progestin
Assessment
Baseline assessment prior to administration:
• Obtain a complete health history including cardiovascular, peripheral vascular, thyroid, hepatic, or kidney disease; migraine headaches; diabetes;
pregnancy; or breastfeeding. Note personal or family history of thromboembolic disorders (e.g., MI, stroke, peripheral vascular disease) and of
reproductive cancers (e.g., breast, uterine, or ovarian cancer).
• Obtain a drug history including allergies, current prescription and OTC drugs, herbal preparations, alcohol use, and smoking. Be alert to possible drug
interactions.
• Evaluate appropriate laboratory findings (e.g., CBC, platelets, electrolytes, glucose, lipid, and thyroid function levels), Pap test, HPV screening,
pregnancy test.
• Obtain baseline height, weight, and vital signs.
• Assess the patient’s ability to receive and understand instructions. Include family and caregivers as needed.
Assessment throughout administration:
• Assess for desired therapeutic effects (e.g., symptoms of menopause or ease of dysfunctional uterine bleeding).
• Continue periodic monitoring of CBC, platelets, and thyroid function studies.
• Monitor vital signs and weight at each healthcare visit.
• Assess for adverse effects: nausea, vomiting, headache, weight gain, breast tenderness, skin rash, acne, fluid retention, changes in mood, midcycle
breakthrough bleeding. Immediately report tachycardia, palpitations, HTN, especially associated with angina, severe headache, cramping in calves,
chest pain, or dyspnea.
Implementation
Interventions and (Rationales) Patient-Centered Care
Ensuring therapeutic effects: • Instruct the patient to take the drug at the same time daily to help with
• Monitor appropriate medication administration for optimal results. remembering to take the pill. Do not omit doses or increase or
decrease dose without consulting the healthcare provider. Omitting
(Maintaining consistent daily doses for treatment of menopausal doses increases the risk of breakthrough bleeding.
symptoms or dysfunctional uterine bleeding will ensure that hormone
levels stay stable and symptoms ease.)
Minimizing adverse effects: • Instruct the patient to immediately report:
• Monitor for symptoms of cardiopulmonary, cerebrovascular, and • Dyspnea, chest pain, or blood in sputum (possible pulmonary
embolism)
peripheral vascular thromboembolism. Monitor blood pressure at each • Heaviness, chest pain, or an overwhelming feeling of fatigue and
clinical visit. (Thromboembolic events are a possible adverse effect of weakness accompanied by nausea and diaphoresis (possible MI)
progestin drugs. The risk increases with age over 35, in women with a • Sudden, severe headache, especially if associated with a
previous history of cardiovascular disease, and in women who smoke. preheadache aura, dizziness, difficulty with speech, numbness in
Monitor for symptoms of peripheral thrombophlebitis, pulmonary arm or leg, difficulty with vision (possible stroke)
embolism, MI, stroke, or other complications related to blood clots.) • Warmth, redness, swelling, or tenderness in calf or pain on walking
(possible thrombophlebitis).
• Teach the patient to monitor blood pressure periodically and report any
blood pressure above 140/90 mmHg or per parameters set by the
healthcare provider.
Chapter 69 Estrogens, Progestins, and Drugs Modifying Uterine Function 1271
CONNECTIONS: NURSING PRACTICE APPLICATION (continued)
Implementation
Interventions and (Rationales) Patient-Centered Care
• Encourage smoking cessation and provide information about smoking • Advise the patient of the risk of smoking while using progestins and
cessation programs. (Smoking greatly increases the risk of adverse discuss smoking cessation programs, providing referral to appropriate
effects of hormone therapy.) support groups and literature on smoking cessation programs.
• Assess for the presence of bone or musculoskeletal pain on each • Instruct the patient to immediately report any sudden and severe pain,
healthcare visit, especially in patients taking injectable progestins. or continuous moderate pain, in joints or muscles, loss of motion, or
(Progestins are associated with an increased risk of loss of bone difficulty with ambulation or movement to the healthcare provider.
density. Bone density monitoring, e.g., DEXA scan, may be ordered
periodically. Immediately report any sudden, severe pain or difficulty
with ambulation or movement.)
• Lifespan: Monitor mental status in patients age 65 or older or patients • Instruct the patient, family, or caregiver to promptly report any changes
with a history of depression or psychiatric illness. (Progestins are in behavior, depression, or mental status to the healthcare provider.
associated with increased risk of dementia in women age 65 or older.)
• Monitor concurrent drug therapy and any new prescriptions received. • Teach the patient to advise all healthcare providers of the use of
(Many drugs decrease or alter the effectiveness of progestins including progestins before beginning any new prescription.
drugs in the penicillin, barbiturate, antiseizure, antidepressant, and
benzodiazepine classifications. Check for drug interactions that may
affect hormone effectiveness before any new prescription is started.)
• Monitor Pap tests, HPV screening, and breast examinations as • Teach the patient how to perform breast self-examinations, noting that
ordered. (Pap tests and breast examinations, including mammography monthly examinations may not be recommended by the healthcare
as appropriate, will monitor for the development of breast tumors or of provider except for women at high risk for breast cancer. For women
cervical cancer.) over age 40, advise the patient on the need for follow-up
mammography per healthcare provider recommendations.
• Advise the patient on the need for annual gynecologic examinations to
ensure continued health. Frequency may be decreased after age 65
after consultation with the healthcare provider.
• Monitor for the occurrence of any breakthrough bleeding. Report any • Teach the patient that slight spotting may occur midcycle while on
continuous, unusual, or heavy bleeding. (Small amounts of spotting progestin but to report any unusual changes in the amount or if the
may occur, especially with low-dose hormone therapy, at midcycle. bleeding continues.
Any continuous, unusual, or heavy bleeding may indicate adverse
effects or disease and should be reported.)
Patient understanding of drug therapy: • The patient should be able to state the reason for the drug, appropriate
• Use opportunities during administration of medications and during dose and scheduling, what adverse effects to observe for, and when
to report them.
assessments to discuss the rationale for drug therapy, desired
therapeutic outcomes, commonly observed adverse effects,
parameters for when to call the healthcare provider, and any necessary
monitoring or precautions. (Using time during nursing care helps to
optimize and reinforce key teaching areas.)
Patient self-administration of drug therapy: • Teach the patient to take the drug following appropriate guidelines:
• When administering the medication, instruct the patient or caregiver in • Oral drugs should be taken at the same time each day to help
remember the dose. Follow instructions if dose is missed.
proper self-administration of the drug, e.g., consistently at the same • Take the drug with food or milk to decrease the possibility of
time each day to help remember the dose, followed by teach-back. nausea.
(Utilizing time during nurse administration of these drugs helps to
reinforce teaching.)
Hormone Replacement Therapy symptoms that include hot flashes, night sweats, irregular
menstrual cycles, vaginal dryness, and bone mass loss.
69.4 Hormone replacement therapy provides
relief from menopause symptoms but may have PharmFACT
serious long-term negative effects.
Women who enter menopause at an early age (40–45 years) are
Menopause is characterized by a progressive decrease in at increased risk for developing future heart failure. Smoking
estrogen secretion by the ovaries resulting in the perma- can increase this risk, even for women who enter menopause
nent cessation of menses. The climacteric is the period of from ages 46 to 49 (Rahman, Åkesson, & Wolk, 2015).
endocrine, somatic, and psychologic changes that occur
during the transition to menopause. There are over 30 mil- During the past 40 years, healthcare providers have
lion menopausal women in North America and each commonly prescribed hormone replacement therapy
decade millions more reach the climacteric. Menopause is (HRT) during menopause. HRT supplies physiologic
neither a disease nor a disorder, but is a natural conse- doses of estrogen, sometimes combined with a proges-
quence of aging that is often accompanied by unpleasant tin, to treat unpleasant symptoms of menopause and to
1272 Unit 10 Pharmacology of the Endocrine System
Table 69.2 Potential Consequences of Estrogen Loss • Women taking estrogen alone experienced an increased
risk of stroke and other thromboembolic disorders.
Related to Menopause
• Women taking estrogen alone did not experience an
Stage Symptoms and Conditions increased risk of breast cancer or MI.
Early menopause
Headaches The adverse effects documented in the WHI study and
Hot flashes others were significant enough to suggest that the potential
Insomnia benefits of long-term HRT may not outweigh the risks for
Irregular menstrual cycles many women.
Mood disturbances, depression, irritability
To be clear, HRT does offer relief from the immediate,
Midmenopause Sexual disinterest distressing vasomotor menopausal symptoms, prevents
Postmenopause Skin atrophy osteoporosis-related fractures, and may offer some degree
Stress urinary incontinence of protection from colorectal cancer. These are certainly sig-
Vaginal atrophy, increased infections, painful nificant and important benefits from HRT. The risks of HRT
intercourse include increased incidence of MI, thromboembolic events,
breast cancer (estrogen–progestin combinations), ovarian
Alzheimer’s-like dementia cancer (estrogen alone), and possibly dementia, urinary
Cardiovascular disease incontinence, and gallbladder disease. Until research pro-
Colon cancer vides more definitive answers, the choice of HRT to treat
Osteoporosis menopausal symptoms remains a highly individualized
one, between the patient and her healthcare provider.
prevent the long-term consequences of estrogen loss
listed in Table 69.2. In recent years, several drugs have been marketed to
treat symptoms of menopause while lowering the potential
Beginning in the mid-1960s, large numbers of peri- adverse effects of estrogen–progestin combinations. Dua-
menopausal and menopausal women received conjugated vee is a combination drug that contains conjugated estro-
estrogen (Premarin). Premarin was widely prescribed, gens with bazedoxifene, which belongs to a class of drugs
despite a lack of research on its effectiveness and long-term called selective estrogen receptor modifiers (SERMs). Dua-
effects. The drug’s popularity extended several more vee offers the advantages of preventing intense hot flashes
decades, making Premarin one of the most frequently pre- (the estrogen component) while reducing the risk of osteo-
scribed medications in the United States. In addition, a sig- porosis-related fractures that are common in postmeno-
nificant number of women were prescribed conjugated pausal women (the SERM component). Approved in 2013,
estrogens combined with medroxyprogesterone (Prempro). Duavee was the first HRT to include a SERM instead of a
progestin. This drug carries the same black box warning as
In the mid-1970s, however, studies showed that that for conjugated estrogens regarding an increased risk of
women who had used estrogen (without progestin) for endometrial cancer and DVT. Duavee is given by the oral
7 years or longer were more likely to develop uterine route and is pregnancy category X.
(endometrial) cancer. Progestins were then added to the
HRT regimen to lower the risk of endometrial cancer. Another SERM, ospemifene (Osphena), was approved
in 2013 to treat dyspareunia, a type of acute pain in post-
Two large, randomized, double-blind, placebo- menopausal women that may occur during intercourse.
controlled studies have challenged the safety of using HRT Ospemifene acts as an estrogen agonist on the vagina,
during menopause. The Women’s Health Initiative (WHI) increasing the thickness of the vaginal epithelium. This
and the Heart and Estrogen/Progestin Replacement Study drug carries the same black box warning as conjugated
(HERS) helped disprove some of the benefits of HRT for estrogens regarding an increased risk of endometrial can-
postmenopausal women. More than 26,000 women were cer and DVT. Ospemifene is given by the oral route and is
enrolled in these studies, which were discontinued early pregnancy category X.
when it became clear that the potential benefits of long-
term HRT were not being realized. The results of the study In 2016 the FDA approved an additional drug for treat-
depended on whether the HRT consisted of estrogen alone ing dyspareunia caused by postmenopausal vulvar or vag-
or an estrogen–progestin combination. Researchers reached inal atrophy. Prasterone (Intrarosa) is administered as a
the following conclusions: once-daily vaginal insert. This drug consists of dehydro-
epiandrosterone (DHEA), a natural hormone secreted pri-
• Women taking estrogen–progestin combination HRT marily by the adrenal gland. Metabolically, DHEA is
experienced a statistically significant increased risk of converted into androgens and estrogens. It is interesting to
MI, stroke, breast cancer, dementia, and venous throm- note that DHEA is a widely used dietary supplement that is
boembolism. The risks were higher in women older claimed to produce a wide variety of positive effects,
than age 60; women ages 50 to 59 actually experienced
a slight decrease in adverse cardiovascular events.
• Women taking estrogen–progestin combination HRT
experienced a decreased risk of hip fractures and
colorectal cancer.
Chapter 69 Estrogens, Progestins, and Drugs Modifying Uterine Function 1273
including increased muscle strength, memory, and bone fetus in continuing the pregnancy. Parenteral oxytocin
density. Most of these claims have little scientific basis. (Pitocin) may be given to induce labor. Doses in an IV infu-
Although DHEA tablets are available OTC in the United sion are increased gradually, every 15 to 60 minutes, until a
States, its use is banned by world sports organizations. normal labor pattern is established. After delivery, IV oxy-
tocin is administered to control postpartum uterine bleed-
Uterine Stimulants: Oxytocics ing by temporarily restricting blood flow to this organ.
Doses of these drugs are listed in Table 69.3.
69.5 Oxytocics are drugs used to stimulate the
uterus and promote labor and delivery. In postpartum women, oxytocin is released in response
to suckling, whereby it promotes the ejection (letdown) of
Oxytocics are drugs that stimulate uterine contractions milk from the mammary glands. Oxytocin does not increase
and promote the induction of labor. The most widely used the volume of milk production; this function is provided by
oxytocic is the natural hormone oxytocin, which is secreted the pituitary hormone prolactin, which increases the syn-
by the posterior pituitary gland. The target organs for oxy- thesis of milk. Although rare, deficiencies of prolactin can
tocin are the uterus and the breast. Increasing amounts of result in insufficient milk to conduct breastfeeding. The
oxytocin are secreted as the uterus is distended by the actions of oxytocin during breastfeeding are illustrated in
growing fetus. As pregnancy progresses, the number of Figure 69.3.
oxytocin receptors in the uterus increases, making it even
more sensitive to the effects of the hormone. As blood lev- Ergot alkaloids are obtained from a fungus that grows
els of oxytocin rise, uterine smooth muscle is stimulated to on rye plants. These drugs are used as alternatives to oxy-
contract, thus promoting labor and the delivery of the tocin to control postpartum hemorrhage. The primary
baby and the placenta. drug in this class, methylergonovine (Methergine), is
effective at promoting uterine contractions but is rarely
Oxytocin and other uterine stimulants are indicated prescribed due to the risk of serious HTN. Ergot alkaloids
only when there are demonstrated risks to the mother or are also second-line drugs in the pharmacotherapy of
migraines.
Table 69.3 Uterine Stimulants and Relaxants
Drug Route and Adult Dose (Maximum Dose Where Indicated) Adverse Effects
Stimulants (Oxytocics)
oxytocin (Pitocin) To control postpartum bleeding: 10–40 units per infusion pump in 1000 mL Nausea, vomiting, maternal dysrhythmias
of IV fluid at a rate to prevent uterine atony Fetal bradycardia, uterine rupture, fetal
Ergot Alkaloid To induce labor: IV: 0.5–2 milliunits/min, gradually increasing the dose no intracranial hemorrhage, water intoxication,
methylergonovine (Methergine) greater than 1–2 milliunits/min at 30- to 60-min intervals until contraction fetal brain hemorrhage
pattern is established
Prostaglandins Nausea, vomiting, uterine cramping
carboprost (Hemabate) PO: 0.2–0.4 mg bid–qid Shock, severe HTN, severe dysrhythmias
dinoprostone (Cervidil, Prepidil,
Prostin E2) IM (initial): 250 mcg (1 mL) repeated at 1.5- to 3.5-h intervals if indicated by Nausea, vomiting, cramping, diarrhea, fever
Relaxants (Tocolytics) uterine response Uterine laceration, rupture, or hemorrhage
magnesium sulfate Intravaginal insert (Cervidil): 10 mg (1 insert)
Intravaginal gel (Prepidil): 0.5 mg Flushing, sweating, muscle weakness
nifedipine (Adalat, Procardia) Intravaginal suppository: 20 mg (1 suppository) Complete heart block, circulatory collapse,
respiratory paralysis
terbutaline (Brethine) IV: 1–4 g in 5% dextrose by slow infusion (initial max dose: 10–14 g/day, Flushing, sweating, muscle weakness
then no more than 30–40 g/day at a max rate of 1–2 g/h) Complete heart block, circulatory collapse,
respiratory paralysis
PO: Initial dose of 20 mg, followed by 20 mg after 30 min. If contractions
persist, therapy can be continued with 20 mg q3–8h for 48–72 h with a Nervousness, tremor, drowsiness
maximum dose of 160 mg/day Bronchoconstrictions, dysrhythmias, altered
After 72 h, if maintenance is still required, long-acting nifedipine 30–60 mg maternal and fetal heart rates
daily can be used
IV: 2.5–10 mcg/min; increase every 10–20 min; duration of infusion:
12 h (max: 17.5–30 mcg/min)
PO (maintenance dose): 2.5–10 mg q4–6h as long as necessary to delay
preterm labor
Note: Italics indicate common adverse effects. Underline indicates serious adverse effects.
1274 Unit 10 Pharmacology of the Endocrine System
PROTOTYPE DRUG Oxytocin (Pitocin)
Hypothalamus Classification Therapeutic: Drug to induce labor, uterine
sends impulse to stimulant
posterior pituitary
Pharmacologic: Hormone, oxytocic
Hypo- Hunger
thalamus
Posterior Nerve impulses Therapeutic Effects and Uses: Oxytocin (Pitocin),
pituitary sent to hypothalamus identical to the natural hormone secreted by the posterior
pituitary gland, is the preferred drug for inducing labor.
Oxytocin Suckling stimulates Given by IV infusion antepartum, oxytocin induces labor
released nerves in breasts almost immediately by increasing the frequency and force
of contractions of uterine smooth muscle. It is adminis-
Muscles contract, tered during the final stages of labor, after the cervix is
Milk squeeze out milk dilated, membranes have ruptured, and presentation of
gland the fetus has occurred. It is also used to induce labor in
cases of maternal diabetes, preeclampsia, eclampsia, and
Muscle Duct Nipple erythroblastosis fetalis. It should not be used for elective
cell induction of labor, due to potential adverse effects to the
mother or baby.
Milk-producing cell
Oxytocin is also approved to reduce postpartum hem-
Figure 69.3 Oxytocin and breastfeeding. orrhage following expulsion of the placenta and to aid in
returning normal muscular tone to the uterus. This drug is
Several prostaglandins are also used as uterine approved at higher doses for the adjunct management of
stimulants. Unlike most hormones that travel through incomplete or inevitable abortion. Intranasal forms once
the blood to affect distant tissues, prostaglandins act used to promote milk letdown are no longer available in
directly at the site where they are secreted. In the uterus, the United States.
prostaglandins cause intense smooth muscle contrac-
tions. Carboprost (Hemabate) may be used to control Mechanism of Action: Oxytocin increases the inten-
postpartum hemorrhage. Dinoprostone (Cervidil, sity and frequency of uterine smooth muscle contractions.
Prepidil, Prostin E2) is used intravaginally to promote When stimulated by sucking, oxytocin causes smooth
cervical ripening, a softening and dilation of the cervix muscle in alveolar ducts to contract, thus ejecting milk
that must occur prior to vaginal delivery. Misoprostol from the breast.
(Cytotec) is another prostaglandin that has been used
off-label to promote cervical ripening. When used in Pharmacokinetics:
high doses, the prostaglandins can induce pharmaco-
logic abortion (see Chapter 70). Route(s) IV or IM
Absorption Destroyed in the GI tract
Distribution Widely distributed in extracellular
fluid; small amounts may cross the
placenta; secreted in breast milk
Primary metabolism Rapidly destroyed in the kidney
and the liver
Primary excretion Small amounts via the kidney
CONNECTIONS: Patient Safety Onset of action IV: immediate; IM: 3–5 min
Incomplete Medication Order Duration of action Half-life: 3–5 min
It has been a very busy morning on the obstetrics unit with Adverse Effects: The most common adverse effects of
multiple patient discharges and several new admissions. One oxytocin are rapid, painful uterine contractions and fetal
patient is a 35-year-old woman with preeclampsia who is tachycardia. Uterine rupture or fetal trauma from too-
admitted for labor induction with an order that reads “Begin rapid expulsion through the pelvis, seizure, and coma are
oxytocin infusion at 2 milliunits/min and increase by 2 milli- regarded as the most serious adverse effects. The risk of
units/min every 30 min.” The nurse places a call to the obstetri- uterine rupture is increased in women who have deliv-
cian to clarify this. What is missing from this order? ered five or more children. When given IV, vital signs of
the fetus and mother must be monitored continuously to
Answers to Patient Safety questions are available on the faculty prevent fetal complications, such as dysrhythmias or intra-
resources site. Please consult with your instructor. cranial hemorrhage. Black Box Warning: Oxytocin is not
Chapter 69 Estrogens, Progestins, and Drugs Modifying Uterine Function 1275
indicated for the elective induction of labor. Elective induc- Drugs Similar to Oxytocin (Pitocin)
tion is the initiation of labor in a pregnant patient who has
no medical indications for induction. Uterine stimulants also include prostaglandins (carboprost
and dinoprostone) and the ergot alkaloid methylergonovine.
Contraindications/Precautions: Oxytocin has an
antidiuretic effect and care must be taken to avoid water Carboprost (Hemabate): Carboprost, equivalent to endog-
intoxication. Oxytocin is contraindicated when there is enous prostaglandin F2 alpha, is approved for controlling
evidence of fetal distress, placenta previa, uterine pro- postpartum bleeding that has not responded to oxytocin
lapse, active herpes infection, abnormal fetal position, and and for inducing pharmacologic abortion between
cervical cancer. Breastfeeding should be delayed for at weeks 13 and 20 of gestation. For postpartum bleeding, it
least 24 hours after the drug is discontinued. is administered by the IM route every 15 to 90 minutes
until hemorrhage is controlled. Nausea, vomiting, diar-
Drug Interactions: Vasoconstrictors used concur- rhea, and fever are common adverse effects. This drug is
rently with oxytocin may cause severe HTN. Oxytocin pregnancy category C.
may cause adverse cardiovascular effects when adminis-
tered with fibrinolysin, warfarin, and cyclopropane anes- Dinoprostone (Cervidil, Prepidil, Prostin E2): Dinopros-
thesia. Herbal/Food: Ephedra used with oxytocin may tone, or prostaglandin E2, is approved to prepare the cervix
lead to HTN. for labor or to abort a fetus that has died. To promote cervi-
cal ripening, it is administered intravaginally. The gel form
Pregnancy: Category X. of the drug is placed into the cervical canal using prefilled
syringes and doses may be repeated every 6 hours, as
Treatment of Overdose: Overdose will cause severe needed. The vaginal insert releases the drug slowly, over
cramping and possible damage to the uterus. Discontinu- 12 hours. The insert may be quickly and easily removed
ation of the infusion will result in a rapid resolution of once labor begins. Both the gel and the insert may stimu-
symptoms due to the short half-life of the drug. late the uterus to begin contracting. Like carboprost, GI
effects and fever are very common adverse effects. This
Nursing Responsibilities: Key nursing implications drug is pregnancy category C.
for patients receiving oxytocin are included in the Nursing
Practice Application for Patients Receiving Pharmacother- Methylergonovine (Methergine): Ergonovine is an older
apy with Oxytocin (Pitocin). drug, approved in 1946. It may be administered by the PO,
CONNECTIONS: Complementary and Alternative Therapies
Soy as a Phytoestrogen
Description Evidence
Soy, or soybean, is a nutritional food that is a major source of protein Soy is one of the most studied dietary supplements. For
for many cultures, especially those in China and Japan. In the United many years soy was believed to provide superlative health
States, soy has become increasingly popular and is one of the top benefits, including lowering of LDL cholesterol. Both the FDA
10 most utilized supplements. In addition to its nutritional value, soy and the American Heart Association (AHA) recognized the
contains estrogen-like (phytoestrogen) substances known as isofla- use of soy products as providing beneficial results in coro-
vones. Soy milk is made by grinding soybeans into a fine powder, nary heart disease in the 1990s. Eating soy protein as a
which is then mixed with water. Other products include soy sauce, replacement for meat and meat products may reduce the risk
soy flour, tofu, nutritional snack bars, and soy protein drinks. of heart disease and improve heart health. It has also been
shown to reduce hot flashes in menopause, although large-
History and Claims scale studies are inconclusive. Soy isoflavones have antioxi-
dant properties and appear to inhibit angiogenesis and
Soy has been used as a nutritional source for thousands of metastasis. Some studies have found a small reduction in
years. Claims for soy’s benefits include anticancer effects, treat- prostate cancer and breast cancer risk for those who are tak-
ment of osteoarthritis, cholesterol-lowering effects, and reduc- ing soy isoflavones (Chen et al., 2014; Mahmoud, Yang, &
tion of menopausal symptoms. Soy isoflavones have been Bosland, 2014). Soy isoflavones may also be a promising
identified as dietary components that have an important role in supplement for cancer chemoprevention or treatment, but
reducing the incidence of breast and prostate cancers. more research is needed to draw definitive conclusions in
these areas.
Standardization
Standardization of soy is either to the amount of bean extract or
to the amount of isoflavones in the product. The standard dose
has not been established.
1276 Unit 10 Pharmacology of the Endocrine System
IM, or IV routes to control postpartum hemorrhage and CONNECTION Checkpoint 69.2
restore uterine tone. The IV route is used only in emer-
gency situations because it may produce serious HTN or Calcium channel blockers, including nifedipine, are widely used
stroke in the mother. Uterine contractions begin in 3 to to treat cardiovascular disorders. From what you learned in
5 minutes after an IM dose. Cramping and GI-related Chapter 30, what effects would you expect nifedipine to have on
adverse effects are common with this drug. The drug is vascular smooth muscle, myocardial oxygen demand, and myo-
contraindicated during pregnancy because it can cause cardial conduction? Answers to Connection Checkpoint questions
immediate uterine contractions that could injure the fetus. are available on the faculty resources site. Please consult with your
This drug is pregnancy category C. instructor.
CONNECTIONS: NURSING PRACTICE APPLICATION
Patients Receiving Pharmacotherapy with Oxytocin (Pitocin)
Assessment
Baseline assessment prior to administration:
• Obtain a complete health history including current length of pregnancy duration; presence of preeclampsia or eclampsia; recent labor; type of delivery;
history of labors or cesarean births; cardiovascular, neurologic, hepatic, or kidney disease; diabetes; or breastfeeding.
• Obtain a drug history including allergies, current prescription and OTC drugs, herbal preparations, alcohol use, and smoking. Be alert to possible drug
interactions.
• Evaluate appropriate laboratory findings (e.g., CBC, platelets, coagulation studies, electrolytes, glucose, magnesium level, and hepatic and kidney
function studies).
• Obtain baseline height, weight, and vital signs.
• Obtain fetal heart rate, intrauterine positioning.
• Check for presence of cervical dilation and effacement. Monitor quality and duration of any existing contractions. Monitor fetal response to
contractions, noting any sign of fetal distress.
• Check for postpartum bleeding and note the number of pads saturated.
• Assess the patient’s ability to receive and understand instructions. Include family and caregivers as needed.
Assessment throughout administration:
• Assess for desired therapeutic effects (e.g., strong, regular contractions supportive of labor, control of postpartum bleeding).
• Continuously monitor timing, quality, and duration of contractions. Immediately report sustained uterine contractions to the healthcare provider.
• Continuously monitor fetal heart rate and response to contractions. Immediately report signs of fetal distress to the healthcare provider.
• Continue periodic monitoring of CBC, platelets, electrolytes, glucose, and magnesium levels.
• Monitor vital signs frequently and immediately report any blood pressure above 140/90 mmHg or less than 90/60 mmHg, especially if accompanied
by tachycardia, or per set parameters to the healthcare provider.
• Continue to monitor postpartum bleeding and pad count. Notify the healthcare provider if more than two full-size pads are saturated in a 2-h time
period.
• Assess for adverse effects: nausea, vomiting, or headache. Immediately report tachycardia, palpitations, HTN, especially associated with angina,
severe headache, or dyspnea. Immediately report any severe abdominal pain, sustained uterine contraction, diminished urine output, dizziness,
drowsiness, confusion, changes in level of consciousness, or seizures.
Implementation
Interventions and (Rationales) Patient-Centered Care
Ensuring therapeutic effects: • Teach the patient about the rationale for all IV and monitoring
• Monitor appropriate medication administration for optimal results. IV equipment and the need for frequent monitoring to allay anxiety.
oxytocin must be given via infusion pump to allow for precise dosing. • Teach the patient that labor contractions will gradually increase and
(Infusion pumps allow for rapid dosage adjustments to maintain uterine that the drug will be decreased or stopped once contractions reach an
contractions supportive of labor until cervical dilation has reached optimal level.
approximately 5–6 cm.)
• Encourage laboring patients to use pain control measures (e.g.,
therapeutic breathing) or pain control drugs as needed and as ordered.
Minimizing adverse effects: • Teach the patient that labor contractions will increase in strength and
• Monitor timing, quality, and duration of contractions continuously. duration and will be monitored. Instruct the patient to immediately
report any sustained contraction or severe abdominal pain.
Immediately report any sustained uterine contractions to the healthcare
provider. Stop the drug infusion, infuse normal saline or solution as
ordered, and place the patient on her side until follow-up orders are
obtained if sustained contractions continue. (Oxytocin may cause
sustained uterine muscle contractions with potential uterine rupture.
Uterine contractions must be monitored and any continuous, sustained
contractions reported immediately.)
• Continuously monitor the fetal heart rate and response to contractions. • Teach the patient that the fetal heart rate will also be monitored along
Immediately report any signs of fetal distress to the healthcare with uterine contractions. Explain the purpose of all monitoring
provider. (Uterine contractions can affect the amount of blood flow equipment to allay anxiety.
through the placenta with diminished oxygenation to the fetus.
Changes in fetal heart rate may signal fetal distress, and the patient
should be placed on her side, oxygen administered unless otherwise
ordered, the infusion stopped, and the healthcare provider notified.)
Chapter 69 Estrogens, Progestins, and Drugs Modifying Uterine Function 1277
CONNECTIONS: NURSING PRACTICE APPLICATION (continued)
Implementation
Interventions and (Rationales) Patient-Centered Care
• Monitor vital signs and urine output frequently, and immediately report • Instruct the patient to immediately report any headache, dizziness,
any blood pressure above 140/90 mmHg or less than 90/60 mmHg, disorientation or confusion, palpitations, chest pressure, or pain.
especially if accompanied by tachycardia or diminished urine output, to
the healthcare provider. (Oxytocin has vasoconstrictive and water-
retention properties. Blood pressure and heart rate may increase and
water intoxication is a possible adverse effect. Blood pressure or pulse
rate exceeding parameters, increasing disorientation or confusion, and
diminished urine output may signify adverse drug effects or possible
complications.)
• Monitor fundal firmness and location, postpartum bleeding, and pad • Instruct the patient to report any sudden increase in lochia, dizziness,
count. Notify the healthcare provider if more than two full-size pads are lightheadedness, or if more than two pads are saturated after 2 h.
saturated in a 2-h time period. (Oxytocin may be given to control
postpartum bleeding. Lochia that increases, or if two or more pads are
saturated over a 2-h period, should be immediately reported to the
healthcare provider.)
Patient understanding of drug therapy: • The patient should be able to state the reason for the drug, monitoring
• Use opportunities during administration of medications and during needs, what adverse effects to observe for, and when to report them.
assessments to discuss the rationale for drug therapy, desired
therapeutic outcomes, commonly observed adverse effects,
parameters for when to call the healthcare provider, and any necessary
monitoring or precautions. (Using time during nursing care helps to
optimize and reinforce key teaching areas.)
Uterine Relaxants: Tocolytics weighed against their potential adverse effects, which
include tachycardia in both the mother and the fetus.
69.6 Uterine relaxants are used to suppress There is no clear evidence that tocolytics reduce perinatal
preterm labor. or neonatal mortality.
Preterm labor, the initiation of labor prior to week 37 of Only a few drugs are available as tocolytics, and none
gestation, is a major cause of neonatal mortality. The most can be realistically considered a prototype. For over
common cause is premature rupturing of membranes or 30 years, magnesium sulfate was the preferred drug for
infections of the chorion or uterus. If the organ systems of delaying preterm labor, but some evidence suggests that it
the fetus are determined to be immature, attempts may may be ineffective and that it poses undue risks to the fetus
be made to delay labor because preterm infants have a and mother. The only drug that is FDA approved for this
high morbidity and mortality rate. Suppressing labor indication is ritodrine (Yutopar), but it is no longer avail-
allows additional time for the fetal organs to develop and able in the United States. Calcium channel blockers and
may permit the pregnancy to reach normal term. Bedrest beta-adrenergic agonists appear to be effective and are
is mandatory and corticosteroids may be administered to used off-label for this indication. Doses for these drugs are
accelerate fetal lung maturity and reduce the incidence of listed in Table 69.3.
neonatal respiratory distress syndrome. Antibiotics such
as ampicillin or erythromycin are indicated if the preterm Magnesium sulfate: A traditional preferred tocolytic,
labor is due to a uterine or chorionic infection. Preterm magnesium sulfate is administered by continuous IV infu-
labor can be stopped and delivery delayed in about 50% sion via a controlled pump device until preterm contrac-
of women, if the membranes have not yet ruptured. The tions diminish, usually in about 30 minutes. It is used
success rate is only 25% in patients with membrane off-label for this indication. During therapy, careful moni-
rupture. toring of deep tendon reflexes, blood pressure, respirations,
urinary output, and serum magnesium concentrations are
Tocolytics are uterine relaxants prescribed to sup- necessary. Early signs of magnesium overdose include
press preterm labor contractions. Typically, the mother is flushing of the skin, sedation, confusion, intense thirst, and
given a monitor with a sensor that records uterine con- muscle weakness. Extreme levels cause neuromuscular
tractions and this information is used to determine the blockade with resultant respiratory paralysis, heart block,
doses and timing of tocolytic medications. Tocolytics can and circulatory collapse. In 2013, the FDA changed the
generally delay labor by only 24 to 72 hours, but this is pregnancy rating for this drug from A to D and warned
often enough time for the fetus to develop normal lung that use for more than 5 to 7 days in pregnant women may
function. The benefits of these drugs must be carefully result in fetal harm. This drug is featured as a prototype
1278 Unit 10 Pharmacology of the Endocrine System
electrolyte in Chapter 33 for the treatment of magnesium increased heart rate, dysrhythmias, myocardial ischemia,
deficiency. transient hyperglycemia, hypokalemia, and pulmonary
edema. The fetus may experience increased heart
Nifedipine (Adalat, Procardia): Nifedipine is a calcium rate and neonatal hypoglycemia. This drug is pregnancy
channel blocker widely prescribed for the treatment of HTN category C.
and angina. The drug has been used off-label as a tocolytic
as an option to magnesium sulfate. Nifedipine is given Pharmacotherapy of Female
either by the PO or sublingual route. A typical regimen Infertility and Female Sexual
includes a loading dose followed by additional PO doses Desire Disorder
every 15 to 20 minutes until contractions diminish. Nifedip-
ine appears to be as effective as magnesium sulfate and the 69.7 Female infertility may be treated with
beta-adrenergic agonists but exhibits fewer adverse effects. drugs that promote oocyte maturation and
Adverse effects include acute pulmonary edema, dysrhyth- ovulation.
mias, and hypotension. A prototype feature for nifedipine is
presented in Chapter 30. This drug is pregnancy category C. Infertility is defined as the inability to become pregnant
after at least 1 year of frequent, unprotected intercourse.
Terbutaline (Brethine): Terbutaline is a beta2-adrenergic Infertility is a common disorder: 25% of couples experi-
agonist that is FDA approved to treat acute broncho- ence difficulty in conceiving children at some point during
spasm due to asthma. It has been used off-label to sup- their reproductive lifetimes. It is estimated that female
press preterm contractions due to its ability to relax reproductive tract conditions contribute to approximately
smooth muscle. It is given by the subcutaneous route 60% of the infertility disorders. Drugs used to treat female
either by injection every 20 minutes or by using a contin- infertility are listed in Table 69.4. Treatment of male infer-
uous infusion device. It may also be administered orally. tility is presented in Chapter 71.
The FDA has issued a black box warning that administra-
tion of terbutaline for more than 48 to 72 hours during The three primary causes of female infertility are pel-
pregnancy can result in serious adverse reactions, includ- vic infections, physical obstruction of the uterine tubes,
ing death of the fetus. The mother may experience
Table 69.4 Drugs for Female Infertility
Drug Route and Adult Dose (Maximum Dose Where Indicated) Adverse Effects
bromocriptine (Parlodel) PO: 1.25–2.5 mg/daily (max: 2.5 mg bid–tid) Nausea, vomiting, cramping, constipation, drowsiness,
headache, orthostatic hypotension, anorexia
clomiphene (Clomid, Serophene) PO first course: 50 mg/day for 5 days; start on fifth day of cycle GI bleeding, psychosis, seizures, syncope
danazol following start of spontaneous or induced bleeding (with progestin) Weight gain, symptoms of PMS, hot flashes, dermatitis
Blurred vision, ovarian hyperstimulation, cataracts,
Second course if ovulation: Repeat first course until conception or thrombosis of temporal arteries
for 3 cycles
Hirsutism, alopecia, voice deepening, weight gain,
Second course if no ovulation: 100 mg/day for 5 days as above vaginal dryness, reduction in breast size, edema,
(max: 100 mg/day) emotional lability, hot flashes
Thromboembolic events, hepatotoxicity, intracranial
PO: 200–400 mg bid for 3–6 months; may extend to 9 months HTN, fetal toxicity
FSH- and LH-Enhancing Drugs Women: Pelvic pain, depression, fatigue
Ovarian hyperstimulation syndrome
chorionic gonadotropin-HCG IM: 5000–10,000 units 1 day following last dose of menotropins Men: Gynecomastia, acne
(Novarel, Ovidrel, Pregnyl) Aggressive behavior, depression
Headache, nausea, abdominal pain, diarrhea,
follitropin alfa (Gonal-F) Subcutaneous: 75 international units/day initially, then increased by increased infections
follitropin beta (Follistim AQ) 37.5 international units at the end of 14 days. Further 37.5-unit Ovarian hyperstimulation syndrome,
dose increases may be made every 7 days (max: 300 international thromboembolic disorders
units/day)
Subcutaneous: 50–75 international units/day initially, then
increased by 25–50 international units at the end of 14 days
(max: 300 international units/day)
Chapter 69 Estrogens, Progestins, and Drugs Modifying Uterine Function 1279
Table 69.4 Drugs for Female Infertility (continued)
Drug Route and Adult Dose (Maximum Dose Where Indicated) Adverse Effects
Abdominal cramps, fullness, or pain, injection-site
menotropins (Menopur, Subcutaneous: 225 international units initially with 125 international reaction, nausea
Repronex) unit dosage increases not more often than every 2 days Ovarian hyperstimulation syndrome,
thromboembolic disorders, respiratory disorders
urofollitropin (Bravelle) For ovulatory women: subcutaneous: 150 international units once Headache, nausea, abdominal pain, diarrhea,
daily until sufficient follicular development is attained increased infections
GnRH Antagonists For anovulatory women: subcutaneous: 75 international units once Ovarian hyperstimulation syndrome,
cetrorelix (Cetrotide) daily. The dose should not be increased more than twice in any thromboembolic disorders
cycle or by more than 75 international units per adjustment
Hot flashes, headache, menstrual irregularities
Subcutaneous: 0.25 mg/day during the early to midfollicular phase Fetal death, ovarian hyperstimulation syndrome
of the cycle following the initiation of FSH
Women: Headache, depression, sweating, acne,
ganirelix Subcutaneous: 250 mcg once daily during the early to midfollicular vaginitis, vaginal dryness, menstrual irregularities,
GnRH Analogs/Agonists phase of the cycle following the initiation of FSH bone density loss, emotional lability
goserelin (Zoladex) Tumor flare (goserelin, leuprolide)
Subcutaneous implant for endometriosis: 3.6 mg every 28 days Men: Erectile dysfunction, lethargy, gynecomastia
leuprolide (Eligard, Lupron, Subcutaneous implant for advanced carcinoma: 10.8 mg every Heart failure
Viadur) 3 months All patients: Pain at injection site, hot flashes, loss
of libido
nafarelin (Synarel) IM for endometriosis: 3.75 mg every month or 11.25 mg every Bone density loss, fractures
3 months
Subcutaneous for infertility: 0.5–1 mg/day. By day 3 of the
menstrual cycle, the dosage is typically decreased by 50%
Intranasal: 2 inhalations/day (200 mcg/inhalation), one in each
nostril; begin between days 2 and 4 of menstrual cycle (may
increase to 800 mcg/day as 2 inhalations)
Note: Italics indicate common adverse effects. Underline indicates serious adverse effects.
and lack of ovulation. Extensive testing is often necessary management. Ovulation induction protocols are some-
to determine the exact cause, and it is not uncommon to times divided into the following three medication
find multiple etiologies for the infertility. groups, which are shown in Pharmacotherapy Illus-
trated 69.1:
For women whose infertility is due to inadequate ovu-
lation, pharmacotherapy may be of value. Ovulatory dys- • Drugs used to promote maturation of ovarian follicles
function is defined as the presence of abnormal, irregular, • Drugs used to trigger ovulation at the end of follicular
or absent ovulation. Signs and symptoms of ovulatory dys-
function include irregular or absent menses, excessive maturation
abdominal bloating, and mood lability. Confirmation of the • Drugs that promote ovulation to occur on a regular,
disorder is made by measuring hormone levels.
monthly basis, at the midpoint of the menstrual cycle.
Ovulatory dysfunction may occur at the level of the
hypothalamus, pituitary, or ovary, and pharmacotherapy Promotion of follicle maturation: Ovulation cannot
is targeted to the specific cause of the dysfunction. The occur unless the ovarian follicles receive a hormonal sig-
most common etiology of ovulatory dysfunction is poly- nal to mature each month. This signal is normally sup-
cystic ovary syndrome, a condition in which the ovaries plied by LH and FSH during the first few weeks of the
are filled with follicular cysts and the patient has elevated menstrual cycle. Clomiphene (Clomid, Serophene) is the
levels of androgens and estrogen. Hirsutism is commonly traditional preferred drug for treating female infertility
observed in these women due to the excessive androgen because it stimulates the release of LH, resulting in the
levels. Another cause of ovulatory dysfunction is hyperp- maturation of more ovarian follicles than would normally
rolactinemia, excessive levels of the hormone prolactin, occur. The rise in LH level induced by clomiphene is suf-
which is most frequently caused by a tumor of the pitu- ficient to induce ovulation in about 80% of treated
itary gland. patients. The use of clomiphene assumes that the pitu-
itary gland is able to respond by secreting LH, and that
Many women with ovulatory dysfunction can be the ovaries are responsive to LH. If either of these
successfully treated with drug therapy; restoring regu- assumptions is false, other treatment options must be
lar, monthly ovulation is an essential goal of fertility considered.
1280 Unit 10 Pharmacology of the Endocrine System
Pharmacotherapy Illustrated 69.1
Mechanisms of Action of Drugs Used to Treat Female Infertility
5 Hypothalamus
Antiestrogens shut off negative
feedback to the hypothalamus, GnRH 1
allowing more secretion of LH and
a greater chance of ovulation GnRH analogs desensitize pituitary GnRH receptors,
• Clomiphene resulting in sharply reduced levels of estrogen
• Goserelin, leuprolide, nafarelin
2
Pituitary
2
GnRH antagonists block GnRH receptors in the pituitary
to inhibit premature LH surge and allow follicles to finish
1 maturing and normal ovulation to occur
• Cetrorelix, ganirelix
Negative LH FSH 4
feedback
3 Similar to FSH, these
2 Similar to LH, this drug drugs stimulate maturation
induces ovulation of ovarian follicles
• Chorionic gonadotropin • Follitropins, menotropins
Ovary
If the infertility is a result of endocrine disruption at Promotion of ovulation: Unless maturing follicles
the pituitary level, therapy with human menopausal receive the final “burst” of LH, ovulation will not occur.
gonadotropin (HMG) or GnRH may be indicated. These HMG is similar in structure to natural LH and produces
therapies are generally indicated only after clomiphene has the same effect: ovulation.
failed to induce ovulation. Also known as menotropins
(Menopur, Repronex), HMG acts on the ovaries to increase Restoration of a normal monthly pattern of ovula-
follicle maturation and results in a 25% incidence of multi- tion: The success of conception will be improved if a
ple pregnancies. Successful therapy with HMG assumes regular, monthly pattern of ovulation is established. Pre-
that the ovaries are responsive to LH and FSH. Newer for- mature ovulation, the expulsion of the oocyte from the
mulations use recombinant DNA technology to synthesize ovary before it has fully matured, is prevented by the use
gonadotropins containing nearly pure FSH, rather than of two antagonists of GnRH: ganirelix and cetrorelix
extracting the FSH-LH mixture from urine. (Cetrotide).
Chapter 69 Estrogens, Progestins, and Drugs Modifying Uterine Function 1281
Stimulation of the ovary by certain fertility drugs causes Therapeutic Effects and Uses: Approved in 1967,
the ovaries to enlarge. Mild enlargement may cause pelvic clomiphene is a first-line drug for female infertility caused
pain but is generally benign and disappears when therapy is by ovulatory dysfunction. It acts by inducing ovulation in
discontinued. One serious complication of certain fertility anovulatory women. The pregnancy rate of patients taking
drugs is ovarian hyperstimulation syndrome (OHS). The clomiphene is high, and twins occur in about 3% to 5% of
onset of OHS is characterized by rapid, massive enlarge- treated patients. Therapy is usually begun with a low dose
ment of the ovaries accompanied by nausea, vomiting, rapid for 5 days following menses because this is the time of
weight gain, ascites, respiratory difficulties, increased risk of greatest follicle maturation. If ovulation does not occur, the
thromboembolism, and progressive kidney impairment. dose is increased. If ovulation still is not induced, HCG is
Progressive symptoms call for discontinuation of drug ther- added to the regimen. If pregnancy has not occurred fol-
apy, fluid restriction, bedrest, and symptomatic treatment of lowing six cycles of successful ovulation, the drug is usu-
nausea, vomiting, and pain. Although OHS can be fatal, ally discontinued and other means of restoring fertility are
most cases resolve in 1 to 2 weeks. explored. The use of clomiphene does not permanently
restore normal follicle maturation. Its effects diminish once
Endometriosis, a cause of infertility, is characterized the drug is discontinued.
by the presence of endometrial tissue that has implanted
outside the uterus in locations such as the surface of pelvic Clomiphene is used off-label to treat low sperm counts
organs or the ovaries. Approximately 25% to 50% of infer- (oligospermia) in men. Just as in women, the drug increases
tile women have endometriosis. Being responsive to hor- the secretion of LH. In men, LH stimulates the testes to pro-
monal stimuli, this abnormal tissue can cause pain, duce testosterone and additional sperm.
dysfunctional uterine bleeding, and dysmenorrhea. The
pain, discomfort, and infertility brought on by endometrio- Mechanism of Action: Clomiphene is a SERM that
sis may be treated by danazol, nafarelin, and leuprolide. has both estrogen agonist and antagonist effects, depend-
These drugs suppress the production of estrogen and pro- ing on the tissue. In the pituitary and hypothalamus, clomi-
gesterone, resulting in a decrease in growth potential of phene acts as an “antiestrogen,” shutting off LH secretion,
endometrial tissues. Surgical removal, ablation, or laser which is required for ovulation. Clomiphene competes
vaporization of the abnormal endometrial lesions may be for estrogen receptors in the hypothalamus by sending a
necessary. Women who have completed their childbearing message that estrogen levels are low; in response, LH is
or who are postmenopausal may consider a hysterectomy secreted, leading to ovarian stimulation.
with oophorectomy.
Pharmacokinetics: PO
Leuprolide (Lupron) and nafarelin (Synarel) are GnRH Route(s)
agonists that produce an initial release of LH and FSH, fol- Absorption Readily absorbed
lowed by suppression due to the negative feedback effect Distribution
on the pituitary. Many women experience relief from the Crosses the placenta; unknown
symptoms of endometriosis after 3 to 6 months of leupro- Primary metabolism if secreted in breast milk; 90%
lide therapy, and the benefits may extend well beyond the Primary excretion bound to protein
treatment period. As an alternative choice, danazol is an Onset of action
anabolic steroid that suppresses FSH production, which in Duration of action Hepatic
turn shuts down both ectopic and normal endometrial
activity. While leuprolide is given only by the parenteral Feces; small amounts in urine
route, danazol is given orally. Estrogen–progestin oral con-
traceptives are also useful in treating endometriosis. 30–60 min
PharmFACT Half-life: 5–7 days; peak effects:
4–10 days
The most important preventable causes of infertility are
chlamydia and gonorrhea infections. These infections can Adverse Effects: Few serious adverse effects occur
cause pelvic inflammatory disease, which can lead to during clomiphene therapy. The most common are
infertility and ectopic pregnancies (Centers for Disease weight gain, symptoms of PMS, hot flashes, allergic der-
Control and Prevention, 2016). matitis, and urticaria. The most serious adverse effects
are blurred vision, ovarian hyperstimulation, cataracts
PROTOTYPE DRUG Clomiphene (Clomid, Serophene) and other visual impairments, and thrombosis of tem-
poral arteries. The drug may cause ovarian enlargement
Classification Therapeutic: Infertility drug with subsequent pelvic pain in about 14% of women tak-
Pharmacologic: Ovarian stimulant ing the drug.
Contraindications/Precautions: Clomiphene
should be avoided in patients with lactation, gyneco-
mastia, fibrocystic breast disease, liver disease, ovarian
cysts not due to polycystic ovary syndrome, and hepatic,
1282 Unit 10 Pharmacology of the Endocrine System
thyroid, or adrenal dysfunction. The drug is contraindi- Drugs Similar to Clomiphene
cated in patients with dysfunctional uterine bleeding until
the cause can be determined. Pregnant patients must not (Clomid, Serophene)
take this drug.
Other drugs for female infertility include bromocriptine,
Drug Interactions: Androgens will reduce the suc- cetrorelix, chorionic gonadotropin-HCG, danazol, follitropins,
cess of clomiphene therapy. Herbal/Food: Black cohosh ganirelix, goserelin, leuprolide, menotropins, and nafarelin.
and chasteberry have estrogen effects that may reduce the
effectiveness of clomiphene. Bromocriptine (Parlodel): Approved in 1978, bromocriptine
is chemically related to the ergot alkaloids and is indicated for
Pregnancy: Category X. a large number of diverse conditions. The drug is a dopamine
agonist, activating dopaminergic receptors in the hypothala-
Treatment of Overdose: Symptoms of overdose mus. For infertility, its primary use is to treat prolactin-
include nausea or vomiting, visual blurring, hot flashes, secreting tumors of the pituitary, which often cause
and pelvic pain. The patient is treated symptomatically. amenorrhea and female infertility. Normal menses are usually
restored after 6 to 8 weeks of therapy. This reduces elevated
Nursing Responsibilities: serum prolactin levels and restores ovulation and ovarian
function in amenorrheic women. It is used as a short-term
• Prior to beginning therapy, obtain a pregnancy test to treatment for amenorrhea in the absence of pituitary tumors.
confirm that the patient is not pregnant. This is a cate- It is also approved to treat acromegaly and Parkinson’s dis-
gory X drug that could cause fetal abnormalities. ease and to improve glycemic control in patients with type 2
diabetes. Off-label indications include mastalgia associated
• Assess for abnormal vaginal bleeding. If present, with PMS, alcoholism, cocaine withdrawal, and neuroleptic
ensure that neoplastic lesions are not present prior to malignant syndrome. Bromocriptine causes frequent adverse
initiating therapy. effects that include nausea, vomiting, cramping, constipation,
drowsiness, headache, orthostatic hypotension, and anorexia.
• Prior to initiating therapy, exclude other causes of This drug is pregnancy category C.
infertility, such as thyroid disorders, adrenal disor-
ders, hyperprolactinemia, and male factor infertility. Cetrorelix (Cetrotide): Approved in 2000, cetrorelix is a
GnRH antagonist given by the subcutaneous route that
• Monitor laboratory results for increased levels of FSH blocks GnRH receptors in the pituitary. Women undergoing
and LH, and pregnancy. ovarian stimulation with FSH or menotropins therapy expe-
rience a sharp rise in estrogen levels due to the maturing fol-
• Counsel patients regarding the timing of drug therapy licles, which can trigger an early surge of LH and premature
and intercourse to achieve pregnancy. ovulation. Cetrorelix inhibits this premature LH surge in
women who are undergoing controlled ovarian stimulation
• Monitor for signs of ovarian hyperstimulation syn- for assisted reproduction, thus allowing follicles to finish
drome such as rapid weight gain, increased abdomi- maturing and normal ovulation to occur. The only indica-
nal girth, nausea, vomiting, dyspnea, and chest pain. tion for cetrorelix is infertility. Adverse effects are minor and
Report symptoms immediately to the prescriber. include hot flashes and headache. It is contraindicated for
use in primary ovarian failure, chronic kidney disease
Patient and Family Education: (CKD), and pregnancy. This drug is pregnancy category X.
• Record basal temperature at the same time each day Chorionic gonadotropin-HCG (Novarel, Ovidrel, Pregnyl):
on a graph to determine if ovulation has occurred. This drug has two forms. HCG is secreted by the placenta
Ovulation occurs on days 4 through 10 in women who and obtained and purified from the urine of pregnant
respond to treatment. There is an increased possibility women. Choriogonadotropin alfa (r-HCG, Ovidrel) is a
of a multiple pregnancy. recombinant form with actions identical to those of HCG.
The chorionic gonadotropin drugs have the same actions as
• Take the medication at the same time each day to LH and can mimic the LH surge that normally causes ovu-
maintain consistent drug levels. lation. As part of an assisted reproductive program, chori-
onic gonadotropin is administered at midcycle, after
• Discontinue the drug and notify the healthcare pro- clomiphene or FSH has been used to mature sufficient
vider if pelvic pain or abdominal distention occurs. numbers of ovarian follicles. A single IM dose is sufficient
This may indicate ovarian enlargement or presence of to induce ovulation. The drug has few adverse effects when
a ruptured ovarian cyst. administered as a single dose in women. This drug is
pregnancy category X.
• Immediately report blurred vision, spots or flashes in
the eyes, severe hot flashes, uterine bleeding, head-
ache, and nausea to the healthcare provider.
• Report signs of jaundice such as yellowing of the skin
or eyes, light-colored stool, and fever.
• Immediately notify the healthcare provider of any
known or suspected pregnancy.
Chapter 69 Estrogens, Progestins, and Drugs Modifying Uterine Function 1283
In males, HCG is approved to treat prepubertal crypt- “on–off” pulsatile manner, which stimulates the release of
orchidism, hypogonadism, and oligospermia. Therapy in LH and FSH (and eventually estrogen). Like GnRH, gosere-
males may continue for several months and gynecomastia, lin first stimulates LH and FSH secretion. With continuous
acne, and behavioral changes may occur. administration, however, the pituitary receptors become
insensitive to the effects of GnRH and the gland stops releas-
Danazol: Danazol is a PO drug used to treat endometriosis. ing LH and FSH. Without FSH or LH, the levels of estrogen
Approved in 1976, the drug exerts antiestrogenic and weak in women and testosterone in men fall dramatically. This
androgenic properties, which cause ectopic endometrial tis- hypoestrogenic state relieves the symptoms of endometrio-
sue to atrophy. After 6 weeks of therapy, danazol causes sis. It is also approved for palliative treatment of estrogen-
anovulation and amenorrhea, which are its therapeutic dependent breast cancer and for advanced prostate cancer.
effects. When the drug is discontinued, normal ovulation Goserelin is available subcutaneously as a once-monthly
and menstrual cycles return in about 2 to 3 months. Danazol implant (for men or women) and a 3-month implant for men
is also approved to treat fibrocystic breast disease and for the with prostate cancer. Women may experience hypoestro-
prophylaxis of hereditary angioedema. The drug has andro- genic effects such as vaginal dryness, depression, menstrual
genic actions that may cause permanent masculinization irregularities, bone density loss, emotional lability, and hot
effects such as hirsutism, alopecia, voice deepening, and flashes. Men may experience erectile dysfunction, gyneco-
weight gain. Women may experience effects of estrogen defi- mastia, and loss of libido. Pain at the injection site is com-
ciency such as vaginal dryness, reduction in breast size, emo- mon. This drug is pregnancy category X.
tional lability, and hot flashes. Serious adverse effects include
thromboembolism, hepatic adenoma, and intracranial HTN. Leuprolide (Eligard, Lupron, Viadur): Like goserelin, leu-
This drug is pregnancy category X. prolide is a GnRH agonist. The two drugs act by the same
mechanism: desensitizing pituitary GnRH receptors,
Follitropins: The follitropins are three different drugs with resulting in sharply reduced levels of estrogen and testos-
the same actions. All are versions of human FSH. Urofolli- terone. For relief of endometriosis symptoms, a depot IM
tropin (Bravelle) is FSH purified from the urine of post- injection is given once monthly or once every 3 months,
menopausal women. Follitropin alfa (Gonal-F) and depending on the dose. Treatment of endometriosis is
follitropin beta (Follistim AQ) are FSH obtained through limited to 6 months. Like goserelin, it is also approved for
recombinant DNA technology. All three FSH products are the palliative treatment of advanced prostate cancer and
given by the parenteral route. The function of FSH (and the used off-label for breast cancer. Leuprolide is an orphan
follitropins) is to stimulate the maturation of ovarian folli- drug for treating precocious (early) puberty in children
cles. The drugs are given early in the menstrual cycle, fol- less than 9 years old. The drug was once widely used to
lowed by a dose of chorionic gonadotropin, which provides treat infertility by inhibiting premature LH surges but the
the boost for ovulation. Multiple births, including triplets, GnRH antagonists are now used for this indication. The
quadruplets, and quintuplets, are common during therapy adverse effects are the same as those for goserelin. This
with follitropins. In men, follitropins are used to stimulate drug is pregnancy category X.
spermatogenesis in patients with hypogonadism and oligo-
spermia. Minor adverse effects include headache, nausea, Menotropins (Menopur, Repronex): Approved in 1975,
abdominal pain, diarrhea, and increased infections. The menotropins is sometimes referred to as HMG. Menotro-
most serious potential adverse effects are OHS, thromboem- pins is a product containing a combination of FSH and LH
bolism, acute respiratory distress syndrome, and exacerba- purified from the urine of postmenopausal women. The
tion of asthma. The follitropins are pregnancy category X. FSH activity of menotropins is significantly higher than its
LH activity. Like the follitropins, menotropins is given by
Ganirelix: Like cetrorelix, ganirelix is a GnRH antagonist the parenteral route during the first half of the menstrual
given by the subcutaneous route that blocks GnRH recep- cycle to promote follicle maturation. At the end of therapy,
tors in the pituitary. Approved in 1999, its only indication is HCG is often administered to supply the LH surge neces-
for female infertility. Ganirelix inhibits the premature LH sary for ovulation. Menotropins therapy is associated with
surge in patients undergoing controlled ovarian stimulation a 20% to 35% possibility of multiple births. In men, meno-
for assisted reproduction. Adverse effects are minor and tropins is FDA approved to stimulate spermatogenesis in
include hot flashes, menstrual irregularities, and headache. patients with hypogonadism and oligospermia. In men,
It is contraindicated for use in primary ovarian failure, gynecomastia, acne, and behavioral changes may occur. In
CKD, and pregnancy. This drug is pregnancy category X. women, the drug often causes ovarian enlargement and
OHS is possible. Serious pulmonary conditions such as
Goserelin (Zoladex): Goserelin is a GnRH hormone agonist. acute respiratory distress syndrome and exacerbation
It has the same physiologic actions as endogenous GnRH; of asthma have been reported. This drug is pregnancy
however, the way it is administered causes the opposite category X.
effect. Natural GnRH is released by the hypothalamus in an
1284 Unit 10 Pharmacology of the Endocrine System
Nafarelin (Synarel): Like goserelin and leuprolide, marked by a persistent lack of interest in sexual activity
nafarelin is a GnRH agonist. The three drugs act by the over a prolonged period. To be diagnosed with HSDD,
same mechanism: desensitizing pituitary GnRH receptors, the patient must be experiencing marked distress
resulting in sharply reduced levels of estrogen and testos- or interpersonal difficulty that negatively impacts her
terone. Unlike the other GnRH analogs, nafarelin is quality of life.
applied topically to the nasal mucosa, where the drug is
rapidly absorbed. When used to treat endometriosis, the In 2015 the FDA approved the first drug for female
typical dose is one spray in each nostril daily. It is also HSDD. Flibanserin (Addyi) is approved to treat HSDD in
approved to treat precocious puberty and used off-label premenopausal women who previously had no problems
for hirsutism. Nafarelin may be used off-label to prevent with sexual desire. The drug carries a black box warning
premature LH surges in women with infertility; however, that it can cause severe hypotension and syncope if taken
ganirelix and cetrorelix are more frequently prescribed for concurrently with alcohol or moderate or strong inhibitors
this indication. Adverse effects are the same as those of the of CYP3A4, such as azole antifungals, ritonavir, telaprevir,
other GnRH agonists goserelin and leuprolide. This drug or verapamil. Because of the potential for serious hypoten-
was approved in 1990 and is pregnancy category X. sion, the FDA requires prescribers to complete special
training. In addition, pharmacies must be certified to dis-
69.8 Low sexual desire in women may be pense the medication, and patients must sign an agreement
treated with pharmacotherapy. that they understand the adverse effects. Common adverse
effects include dizziness, sleepiness, nausea, fatigue, and
Hypoactive sexual desire disorder (HSDD), also called dry mouth. The mechanism by which flibanserin increases
female sexual interest arousal disorder, is a condition sexual desire is not known.
Understanding Chapter 69
Key Concepts Summary 69.5 Oxytocics are drugs used to stimulate the uterus
and promote labor and delivery.
69.1 Regulation of the female reproductive system is
achieved by hormones from the hypothalamus, 69.6 Uterine relaxants are used to suppress preterm
pituitary gland, and ovary. labor.
69.2 Estrogens are administered as replacement therapy, 69.7 Female infertility may be treated with drugs that
to prevent conception, and for certain neoplasms. promote oocyte maturation and ovulation.
69.3 Progestins are administered to treat dysfunctional 69.8 Low sexual desire in women may be treated with
uterine bleeding, to prevent conception, and for pharmacotherapy.
certain neoplasms.
69.4 Hormone replacement therapy provides relief from
menopause symptoms but may have serious long-
term negative effects.
CASE STUDY: Making the Patient Connection
Remember the patient Maureen John is 46 years old and exhibiting signs of meno-
“Maureen John” at the pause. She reports a change in her menstrual cycle regular-
beginning of the chapter? ity. For the past year, her periods have occurred between 6
Now read the remainder and 8 weeks apart and have lasted only 2 to 3 days. Previ-
of the case study. Based ously, she experienced her periods approximately every 28
on the information days and they lasted from 4 to 5 days. She reports to the
presented within this nurse that she is now feeling easily fatigued, has more
chapter, respond to the mood swings, occasional headaches, hot flashes, insomnia,
critical thinking bouts of depression, and irritability. She is also concerned
questions that follow the about her loss of libido. She admits to smoking half a pack
case study. of cigarettes a day and drinking several cups of coffee
Chapter 69 Estrogens, Progestins, and Drugs Modifying Uterine Function 1285
during work hours. She has a family history of HTN, 2. Create a list of some treatment options for Maureen.
cardiac disease, and diabetes, but she has never been diag-
nosed with any of those disorders. 3. Maureen asks about the precautions related to
suggested treatment options. How would you
A complete history and physical examination, along with respond?
a vaginal examination and a Pap smear were performed.
Answers to Critical Thinking Questions are available on the
Critical Thinking Questions faculty resources site. Please consult with your instructor.
1. Do you think that Maureen is a candidate for hormone
replacement therapy? Why or why not?
Additional Case Study
Prithi Kaur, a 23-year-old woman, and her 25-year-old hus- 2. What instructions would you give to the patient
band attend the infertility clinic for evaluation. Efforts at regarding the administration of this drug?
becoming pregnant naturally for the past 2 years have failed.
They inform the nurse that the husband has a 3-year-old son Answers to Additional Case Study questions are available on
from an earlier relationship. The wife has never conceived. the faculty resources site. Please consult with your instructor.
Both denied any sexually transmitted infections. The patient
is started on clomiphene (Clomid) 50 mg for 5 days.
1. Prithi asks you, the nurse, “What are some causes of
infertility?” How would you respond?
Chapter Review 2. “The drug will be continued for the first 3 months
of pregnancy to guard against miscarriage.”
1. A 52-year-old patient experiencing symptoms of
menopause is interested in taking hormone replacement 3. “You may stay on this indefinitely until pregnancy
therapy (HRT) with conjugated estrogen (Premarin). occurs. There are few adverse effects.”
Which conditions may be a contraindication for HRT
for this patient? (Select all that apply.) 4. “If pregnancy does not occur within six cycles,
other options for treatment will be explored.”
1. History of type 2 diabetes mellitus
2. History of deep vein thrombosis 4. A 48-year-old patient has received a prescription for
3. History of breast cancer with “lumpectomy” medroxyprogesterone (Provera) for treatment of
dysfunctional uterine bleeding. Because of related
treatment adverse effects, the nurse will teach the patient to
4. History of hyperlipidemia, controlled by drug therapy monitor and report which symptoms?
5. History of two cesarean births
1. Insomnia or difficulty falling asleep
2. The nurse is evaluating the effect of an oxytocin infu-
sion in a laboring woman. Which of the following 2. Excessive mouth, eye, or vaginal dryness
indicates that the drug is exerting therapeutic effects?
3. Joint pain or pain on ambulation
1. Hemorrhage is controlled.
2. Contractions are sustained at 60 seconds long. 4. Breakthrough spotting between menstrual periods
3. Contractions are occurring every 4 minutes and
5. The patient informs the healthcare provider that she
lasting 20 seconds. has been trying to become pregnant for more than
4. Milk letdown has begun in preparation for 2 years and has not used any form of contraception.
The healthcare provider prescribes clomiphene
breastfeeding. (Clomid) 50 mg/day for 5 days. The nurse should
instruct the patient to begin taking the drug on the:
3. Which instruction about clomiphene (Clomid) will the
nurse provide to a woman with infertility? 1. First day of the menstrual cycle.
1. “The drug will be taken for a year and then 2. Fifth day of the menstrual cycle.
reevaluated for an increased dose.”
3. Fifth day after ovulation.
4. Last day of the menstrual cycle.
1286 Unit 10 Pharmacology of the Endocrine System 3. Seizure activity
4. Sedation and intense thirst
6. A patient in preterm labor is receiving magnesium
sulfate by IV infusion. Which early sign of magne- See Answers to Chapter Review in Appendix A.
sium toxicity would prompt the nurse to stop the
infusion and notify the provider?
1. Hyperactive patellar reflexes
2. Chest congestion and coughing
References Mahmoud, A. M., Yang, W., & Bosland, M. C. (2014). Soy
isoflavones and prostate cancer: A review of molecular
Centers for Disease Control and Prevention. (2016). STDs mechanisms. The Journal of Steroid Biochemistry and
& infertility. Retrieved from http://www.cdc.gov/std/ Molecular Biology, 140, 116–132. doi:10.1016/j.
infertility/default.htm jsbmb.2013.12.010
Chen, M., Rao, Y., Zheng, Y., Wei, S., Li, Y., Guo, T., & Yin, Rahman, I., Åkesson, A., & Wolk, A. (2015). Relationship
P. (2014). Association between soy isoflavone intake between age at natural menopause and risk of heart
and breast cancer risk for pre- and post-menopausal failure. Menopause, 22, 12–16. doi:10.1097/
women: A meta-analysis of epidemiological studies. GME.0000000000000261
PLoS ONE, 9(2), e89288. doi:10.1371/journal.
pone.0089288
Estephan, A. (2016). Dysfunctional uterine bleeding in
emergency medicine. Retrieved from http://emedicine.
medscape.com/article/795587-overview
Selected Bibliography Joffe, H. V., Chang, C., Sewell, C., Easley, O., Nguyen, C.,
Dunn, S., . . . Beitz, J. (2016). FDA approval of
Belkin, Z. R., Krapf, J. M., & Goldstein, A. T. (2015). Drugs flibanserin—treating hypoactive sexual desire disorder.
in early clinical development for the treatment of New England Journal of Medicine, 374(2), 101–104.
female sexual dysfunction. Expert Opinion on doi:10.1056/NEJMp1513686
Investigational Drugs, 24, 159–167. doi:10.1517/
13543784.2015.978283 Lamont, C. D., Jørgensen, J. S., & Lamont, R. F. (2016). The
safety of tocolytics used for the inhibition of preterm
Chlebowski, R. T., Anderson, G. L., Sarto, G. E., Haque, R., labour. Expert Opinion on Drug Safety, 15, 1163–1173.
Runowicz, C. D., Aragaki, A. K., . . . Manson, J. E. (2016). doi:10.1080/14740338.2016.1187128
Continuous combined estrogen plus progestin and
endometrial cancer: The Women’s Health Initiative Leone Roberti Maggiore, U., & Ferrero, S. (2016). An
randomized trial. Journal of the National Cancer Institute, overview of early drug development for endometriosis.
108(3), djv350. doi:10.1093/jnci/djv350 Expert Opinion on Investigational Drugs, 25, 227–247.
doi.org/10.1517/13543784.2016.1126579
Davidson, M. R., London, M. L., & Ladewig, P. L. (2016).
Maternal newborn nursing and women’s health across the Ross, M. G. (2017). Preterm labor. Retrieved from http://
lifespan (10th ed.). Hoboken, NJ: Pearson. emedicine.medscape.com/article/260998-overview#a6
Hanson, B., Johnstone, E., Dorais, J., Silver, B., Peterson, C.
M., & Hotaling, J. (2017). Female infertility, infertility-
associated diagnoses, and comorbidities: A review.
Journal of Assisted Reproduction and Genetics, 34, 167–177.
doi:10.1007/s10815-016-0836-8
“I really don’t want to ruin my
chances of finishing college by
becoming pregnant right now.
What are my choices?”
Patient “Lila Bastian,” 19 years old
Chapter 70
Drugs for Modifying Conception
Chapter Outline Learning Outcomes
cc Options and Choices for Birth Control After reading this chapter, the student should be able to:
cc Combination Oral Contraceptives
1. Identify the choices available for birth control.
Estrogen–Progestin Combinations
PROTOTYPE Estradiol and Norethindrone 2. Delineate advantages and disadvantages of the
(Ortho-Novum, Others), p. 1292 different contraceptive options.
cc Adverse Effects of Combination Oral Contraceptives
cc Progestin-Only Oral Contraceptives 3. Explain the mechanisms by which estrogens and
cc Long-Acting Reversible Contraceptives progestins prevent conception.
cc Spermicides
PROTOTYPE Nonoxynol-9, p. 1298 4. Compare the safety and effectiveness of different
cc Emergency Contraception birth control methods.
cc Drugs for Pharmacologic Abortion
PROTOTYPE Mifepristone (Mifeprex), p. 1302 5. Compare and contrast the options available for long-
term contraception.
6. Explain the use of drugs for emergency
contraception and for terminating pregnancy.
7. Describe the nurse’s role in the pharmacologic
management of patients who are taking oral
contraceptives.
8. For each of the classes shown in the chapter outline,
identify the prototype and representative drugs and
explain the mechanism(s) of drug action, primary
indications, contraindications, significant drug
interactions, pregnancy category, and important
adverse effects.
9. Apply the nursing process to the care of patients
receiving pharmacotherapy for contraception.
1287
1288 Unit 10 Pharmacology of the Endocrine System
Key Terms emergency contraception progesterone, 1289
(EC), 1300 spermicides, 1298
abortifacients, 1301
chloasma, 1294 long-acting reversible
contraception, 1288 contraceptives (LARCs), 1295
ectopic pregnancy, 1292
About 60 to 70 million women in the United States are of protection or the use of progestin-only types of contracep-
childbearing age (15–44 years). Of these women about tives are safer options. Factors that influence their deci-
62% practice contraception, the use of devices, drugs, or sions include the following:
surgery to prevent pregnancy (Daniels, Daugherty,
Jones, & Mosher, 2015). This chapter discusses the female • Effectiveness of the chosen method
sex hormones that are used to modify conception, • Adverse effects and safety
describes other widely used methods of contraception, • Age
and identifies the nursing connections to patient and • Frequency of intercourse
family education. • Ease of use and the ability to adhere to the required
Options and Choices regimen
for Birth Control • Preexisting medical conditions
• Cultural or religious beliefs.
70.1 Selection of a contraceptive is based on
effectiveness, safety, and personal choice. Women seeking to prevent conception need to discuss
the available options with their healthcare provider. Final
The decision to engage in sexual activity is one of the most decisions on choosing a contraceptive should be made vol-
important decisions in life; the choice affects not just the untarily with full knowledge of its advantages and disad-
partners, but may impact generations to follow. A couple vantages, effectiveness, adverse effects, contraindications,
engaging in intercourse on a regular basis without contra- and potential long-term risks. When the desire to have chil-
ceptive protection has a 90% probability of conceiving a dren in the future no longer exists, sterilization of either the
child over the course of a year. Thus, the voluntary choice male or female partner is the most common and effective
to use contraceptive measures is a critical decision faced by option for birth control. Whatever the choice of birth con-
most women in the childbearing years. trol, personal motivation must be taken into consideration
because it is important that the woman be consistent in
Prior to the 1960s, the three primary methods of avoid- using the chosen method if pregnancy is to be prevented.
ing pregnancy were total abstinence, abstinence during
periods of greatest fertility (rhythm or calendar method), Contraceptives act in different regions of the female
and withdrawal prior to ejaculation (coitus interruptus). reproductive tract. The student should refer to Pharmaco-
The discovery of oral contraceptives and the development therapy Illustrated 70.1 often while reading this chapter to
of long-acting reversible contraceptives (LARCs) have obtain an overall perspective on the sites and mechanisms
given couples more effective choices for birth control. For of contraceptive action.
women unable to take medication for contraception, intra-
uterine devices are safe and effective alternatives. Many Combination Oral Contraceptives
contraceptive options are now available, each having spe-
cific advantages and disadvantages. The primary options, 70.2 The most effective oral contraceptives
their effectiveness, and advantages and disadvantages are include combinations of low-dose estrogens and
listed in Table 70.1. progestins.
Women make personal birth control decisions based The physiology and pharmacologic indications for the
on several factors. The effectiveness for preventing preg- female sex hormones estrogen and progesterone are pre-
nancy and the safety of the medication or device are the sented in Chapter 69. Because estrogen and progesterone
highest priorities. Other factors, however, may be of per- are the two classes of drugs used most frequently for con-
sonal concern. Women who engage in intercourse fre- traception, the student should review that chapter before
quently or who are likely to forget to take their medication proceeding.
may prefer the convenience of the LARCs. For patients
who have a history of thromboembolic disorders, barrier The most widespread pharmacologic use of estrogen
and progesterone is to prevent pregnancy. Estrogen is a gen-
eral term that refers to several female sex hormones. The
Chapter 70 Drugs for Modifying Conception 1289
Table 70.1 Effectiveness of Conception Modifiers
PREGNANCY RATE (%/YEAR)*
Type Description With With Selected Advantages Selected Disadvantages
Perfect Use Typical Use
Hormonal Methods
Combination oral Daily tablets 0.3% 9% Very effective, decreased risk of Fluid retention, venous thromboembolism,
contraceptives 0.5% 9% ovarian and endometrial cancer amenorrhea, nausea, vomiting, irregular
(OCs) 6% bleeding, headache; must be taken daily
No estrogen adverse effects; Less effective than combination OCs;
Progestin-only Daily tablets may be used in women with frequent spotting, amenorrhea, ectopic
OCs history of thromboembolic pregnancy
disease
Progestin injections Every 3 months 0.2% Amenorrhea, irregular bleeding,
Do not have to take daily pills; headache, loss of bone density, may
long-term protection delay return of fertility when discontinued
Similar to OCs; higher risk of
Transdermal Weekly patch 0.3% 9% Do not have to take daily pills; thromboembolic disease compared to
patches easy to apply OCs, irritation at application site
Amenorrhea, irregular bleeding, headache
Subdermal Every 3 years 0.05% 1% Do not have to take daily pills;
12–18% long-term protection Less convenient than hormonal methods
progestin implants
Inexpensive; some protection Ineffective if used without barrier
Barrier and Miscellaneous Methods against sexually transmitted protection; inconvenient; vaginal irritation
infections, no hormonal Allergic reactions, vaginal dryness or
Condoms (male), Coitus based 2–6% adverse effects; few significant irritation; less convenient
diaphragms adverse effects
Irregular bleeding, pelvic pain,
Spermicides Coitus based 18% 28% Inexpensive, no hormonal spontaneous expulsion, uterine
12–24% adverse effects perforation
Contraceptive Coitus based 9–20%
sponge 0.2–0.8% Inexpensive; no hormonal Requires cooperation of partner,
adverse effects; protection inconvenient and ineffective
Intrauterine Mirena, Skyla, 0.2–0.6% lasts 24 h Requires cooperation of partner,
devices/systems Copper T380A; inconvenient and ineffective
every few years Effective, long-term
contraception; decreased
Withdrawal method Coitus based 4% 22% menstrual flow and cramping;
inexpensive; no hormonal
adverse effects (Copper
T380A), quick return of fertility
Free; no adverse effects
Biologic Calendar/ 3–5% 24% Free; no adverse effects
rhythm
*Pregnancy rates from using the various methods listed vary considerably in the scientific literature.
ones used in oral contraceptives are the synthetic estrogens reproductive medicine. The majority of oral contraceptives,
ethinyl estradiol and ethinyl valerate. All estrogens have known as “the pill,” contain combinations of estrogen and
the same pharmacologic actions. progestin. Medications containing estrogen or progestin for
the purpose of preventing pregnancy are sometimes called
Progestin is a general term that refers to synthetic hor- hormonal contraceptives. Approximately 30% of the women
mones that have actions identical to progesterone. Although who choose contraceptive methods select OCs. These inex-
progesterone is the natural progestin secreted by the cor- pensive, readily available drugs are 90% effective at pre-
pus luteum, it is rarely used for contraception. Instead, venting pregnancy when taken daily. They are excellent
synthetic progestins including norethindrone, norgestrel, methods of contraception for women who are healthy and
desogestrel, dienogest, and levonorgestrel are used. The have no contraindications. One advantage of OCs is that
synthetic progestins have a longer half-life than progester- they can be discontinued at any time without long-lasting
one, which allows for the convenience of once-daily dos- adverse effects. In addition, one of the OCs, Natazia, has an
ing. All progestins have the same pharmacologic activity. additional indication: heavy menstrual bleeding.
The first oral contraceptive (OC) was approved by A large number of combination OC preparations are
the U.S. Food and Drug Administration (FDA) in 1960, available, differing in dose and by type of estrogen and
and it was quickly recognized as a landmark discovery in
1290 Unit 10 Pharmacology of the Endocrine System
Pharmacotherapy Illustrated 70.1
Mechanisms of Action of Contraceptives
Intrauterine Progesterone
device (“minipill”)
Oral Uterine tube Ovulation
contraceptives
Oocyte
(egg)
Depo-Provera Uterus
injection Endometrium
Ovary
Contraceptive Contraceptive
patch sponge
Nuva Ring
Spermicide
Sperm
progestin, as listed in Table 70.2. Selection of a specific drug to take the medication daily. If one dose is missed, taking two
is individualized for each patient and determined by which pills the following day usually provides for continuous con-
product gives the best contraceptive protection with the traception. If two consecutive doses are missed, two tablets
fewest adverse effects. Treatment is generally initiated with should be taken on both the day the missed doses are remem-
the lowest dose that effectively provides contraceptive pro- bered and the following day. The regular schedule should
tection. Daily doses of estrogen in OCs have declined from then be continued, but a second method of contraception
150 mcg 50 years ago to about 20 mcg in newer formula- should be used for at least 7 days after restarting the pills. If
tions. This reduction has resulted in a significant decrease 3 or more consecutive days are missed, the patient should
in estrogen-related adverse effects. implement other contraceptive precautions until the regimen
can be restarted in the next monthly cycle. Figure 70.1 shows
Typically, administration of an OC begins on day 5 of a typical monthly OC packet with the 28 pills.
the menstrual cycle and continues for 21 days. During the
other 7 days of the month, the patient takes a placebo. Estrogen–progestin combination OCs act by prevent-
Although the placebo serves no pharmacologic purpose, it ing ovulation. They accomplish this by providing negative
does encourage the patient to take the pills on a daily basis. feedback to the pituitary, which suppresses the secretion of
Some of these placebos contain iron, which replaces iron luteinizing hormone (LH) and follicle-stimulating hormone
lost due to menstrual bleeding. (FSH) near the midpoint of the menstrual cycle. Without the
influence of LH and FSH, the ovarian follicles cannot
A common problem with OCs, and likely the most fre- mature and ovulation is prevented. The estrogen–progestin
quent reason for treatment failure (pregnancy), is forgetting
Chapter 70 Drugs for Modifying Conception 1291
Table 70.2 Selected Oral Contraceptives
Trade Name Estrogen Progestin
Monophasic ethinyl estradiol, 30 mcg desogestrel, 0.15 mg
Desogen ethinyl estradiol, 30 mcg norethindrone, 1.5 mg
Loestrin 1.5/30 Fe ethinyl estradiol, 35 mcg norgestimate, 0.25 mg
Ortho-Cyclen-28 ethinyl estradiol, 30 mcg drospirenone, 3 mg
Yasmin ethinyl estradiol, 50 mcg ethynodiol diacetate, 1 mg
Zovia 1/50E-28
Biphasic ethinyl estradiol, 20 mcg for 21 days; 10 mcg for 5 days desogestrel, 0.15 mg for 21 days
Mircette
Triphasic ethinyl estradiol, 35 mcg norethindrone, 0.5 mg
Ortho-Novum 7/7/7-28 ethinyl estradiol, 35 mcg norethindrone, 0.75 mg
ethinyl estradiol, 35 mcg norethindrone, 1 mg
Ortho Tri-Cyclen ethinyl estradiol, 35 mcg norgestimate, 0.18 mg
ethinyl estradiol, 35 mcg norgestimate, 0.215 mg
Tri-Norinyl-28 ethinyl estradiol, 35 mcg norgestimate, 0.25 mg
ethinyl estradiol, 35 mcg norethindrone, 0.05 mg
Trivora-28 ethinyl estradiol, 35 mcg norethindrone, 0.1 mg
ethinyl estradiol, 35 mcg norethindrone, 0.5 mg
Four-phasic ethinyl estradiol, 30 mcg levonorgestrel, 0.05 mg
Natazia ethinyl estradiol, 40 mcg levonorgestrel, 0.075 mg
ethinyl estradiol, 30 mcg levonorgestrel, 1.25 mg
Progestin Only
Micronor ethinyl valerate, 3 mg —
Nor-QD ethinyl valerate, 2 mg dienogest, 2 mg
Emergency Contraceptive ethinyl valerate, 2 mg dienogest, 2 mg
Plan B and Plan B One Step ethinyl valerate, 1 mg —
None norethindrone, 0.35 mg
None norethindrone, 0.35 mg
None levonorgestrel, 1.5 mg
combination drugs also make the uterine endometrium less The four types of estrogen–progestin OC formulations
favorable to receiving an embryo, thus reducing the likeli- are monophasic, biphasic, triphasic, and a four-phase version.
hood of implantation. In addition, the hormones promote The monophasic OC delivers a constant dose of estrogen and
the formation of a thick cervical mucus that slows sperm progestin throughout the 21-day treatment cycle. In biphasic
transport and inhibits the process that allows sperm to pen- drugs, the amount of estrogen in each pill remains constant,
etrate the ovum. The student should refer to Figure 69.2 in but the amount of progestin is increased toward the end of the
Chapter 69 for a review of the negative feedback control of treatment cycle to better nourish the uterine lining. In tripha-
female reproductive hormones. sic formulations, the amounts of both estrogen and progestin
vary in three distinct phases during the treatment cycle. In
PharmFACT 2010 the first four-phase OC, called Natazia, was introduced.
Natazia contains a synthetic estrogen called estradiol valerate
From 2011 to 2015, 56% of sexually active female teens and a progestin called dienogest; this is the first time this spe-
(ages 15–19) used oral contraceptives to prevent pregnancy. cific combination has been used. The manufacturer claims
The use of emergency contraception in this group increased that this four-phase combination more closely resembles the
from 14% in 2006–2010 to 23% in 2011–2015 (Abma & natural monthly hormonal variation. Natazia was also the
Martinez, 2017). first OC approved to treat heavy menstrual bleeding.
1292 Unit 10 Pharmacology of the Endocrine System
Seasonale is an “extended regimen” OC that consists
of tablets containing levonorgestrel and ethinyl estradiol
that are taken for 84 consecutive days, followed by seven
placebo tablets (without hormones). This allows for con-
tinuous contraceptive protection while extending the time
between menses; only four periods are experienced per
year. Seasonique is similar, but instead of inert tablets for
7 days, the patient takes low-dose estrogen tablets. A lower
dose formulation of Seasonique, called LoSeasonique, is
also available.
PROTOTYPE DRUG Estradiol and Norethindrone
(Ortho-Novum, Others)
Classification Therapeutic: Combination oral
contraceptive
Pharmacologic: Estrogen–progestin
Figure 70.1 An oral contraceptive showing the daily doses and Therapeutic Effects and Uses: The primary use
the different formulation taken in the last 7 days of the 28-day cycle. of Ortho-Novum is to prevent pregnancy, for which it is
about 90% effective. Ortho-Novum is available in mono-
Courtesy of Fuse/Corbis/Getty Images. phasic, biphasic, and triphasic formulations. Off-label indi-
cations for the drug include acne vulgaris (in females who
When discontinuing OCs it may take several months have achieved menarche), endometriosis, hypermenor-
for ovulation to return to normal and for monthly men- rhea, dysfunctional uterine bleeding, and hirsutism related
strual periods to become regular. Some women can con- to hyposecretion of estrogen or oversecretion of andro-
ceive in the first month, whereas others experience a delay gens. Noncontraceptive benefits of Ortho-Novum include
for up to a year before fertility is restored. The length of improvement in menstrual cycle regularity and decreased
contraceptive use does not appear to affect fertility. The incidence of dysmenorrhea.
incidence of miscarriage is not increased in women who
conceive after having taken OCs. Mechanism of Action: Ortho-Novum decreases the
potential for conception by inhibiting ovulation. When the
CONNECTION Checkpoint 70.1 right combination of estrogens and progestins is present in
the bloodstream, the release of FSH and LH is inhibited,
Certain drugs that are used to treat infertility block the negative thus preventing ovulation.
feedback cycle by occupying the estrogen receptors in the hypo-
thalamus. From what you learned in Chapter 69, name the class of Pharmacokinetics:
drugs that can do this and explain how they are used to increase
fertility. Answers to Connection Checkpoint questions are available on Route(s) Oral (PO)
the faculty resources site. Please consult with your instructor.
Absorption 83% (norethindrone) and
Although the main purpose for taking combination OCs is
to prevent pregnancy, there are several other benefits. 47–73% (ethinyl estradiol)
Women who are taking OCs report less painful menstrua-
tion and may have reduced incidences of the following Distribution Widely distributed; secreted in
disorders: ectopic pregnancy, which is the development of
the fetus elsewhere rather than in the uterus; pelvic inflam- breast milk
matory disease (PID); ovarian and endometrial cancer;
colorectal cancer; iron deficiency anemia; and benign Primary metabolism Hepatic and GI mucosa;
breast diseases. Women on OCs also experience a better
regulated menstrual flow and fewer outbreaks of acne. extensively metabolized
Primary excretion Renal and feces
Onset of action 30–60 min
Duration of action Half-life: 3–27 h
Adverse Effects: The most common adverse effects of
Ortho-Novum are nausea, breast tenderness, weight gain,
and breakthrough bleeding. Less common serious adverse
effects include edema, unexplained loss of vision, diplopia,
intolerance to contact lenses, gallbladder disease, nausea,
abdominal cramps, changes in urinary function, dysmen-
orrhea, breast fullness, fatigue, skin rash, acne, headache,
Chapter 70 Drugs for Modifying Conception 1293
vaginal candidiasis, photosensitivity, and changes in uri- CONNECTIONS: Community-
nary patterns. Cardiovascular adverse effects, the most Oriented Practice
serious of all, may include hypertension (HTN) and throm-
boembolic disorders. The estrogen component of the pill Macular Edema in Women on Oral
can lead to venous and arterial thrombosis, which results Contraceptives
in pulmonary, myocardial, and thrombotic strokes.
A higher risk of thromboembolic conditions is associated with
Other conditions that are associated with OCs are OC use. Women are advised to immediately report any signs
abnormal uterine bleeding; benign hepatic adenoma; mul- or symptoms such as calf redness and swelling, chest pain,
tiple births; elevated plasma glucose; retinal disorder; and dyspnea, or severe headache to their provider. Macular
melanoderma, a patchy or generalized skin discoloration edema, secondary to retinal vascular occlusion, is also possi-
caused by increased production of melanin. These condi- ble. If untreated, it may lead to progressive vision loss and
tions, though rare, have been reported, and tend to disap- blindness (Yeh et al., 2015). Because vision loss from macular
pear immediately after discontinuing the use of OCs. Black edema may be insidious or sudden, with or without pain, any
Box Warning: Cigarette smoking increases the risk of seri- decrease in visual acuity while a woman is on OCs should be
ous cardiovascular adverse effects in women taking hor- evaluated by an ophthalmologist and retinal vascular occlu-
monal contraceptives containing estrogen. This risk sion ruled out as a causative factor.
increases markedly with age (over age 35) and with heavy
smoking (more than 15 cigarettes per day). Pregnancy: Category X.
Contraindications/Precautions: There are many Treatment of Overdose: There is no specific treat-
contraindications and precautions regarding the use of ment for overdose. The patient is treated symptomatically.
OCs. The risk of cancer following long-term OC use has
been extensively studied. Because some studies have Nursing Responsibilities: Key nursing implications
shown a small increase in the incidence of breast cancer, for patients receiving conjugated estrogens are included
OCs are contraindicated in patients with known or sus- in the Nursing Practice Application for Patients Receiving
pected breast cancer. The incidences of endometrial and Hormonal Contraceptives.
ovarian cancers, however, are significantly reduced after
long-term OC administration. It is likely that the rela- Drugs Similar to Estradiol and
tionship between the long-term use of these drugs and Norethindrone (Ortho-Novum, Others)
cancer will continue to be a controversial and frequently
researched topic. Obesity is a risk factor for treatment Dozens of different estrogen–progestin combinations are
failure and for increased possibilities of thromboembolic available as OCs. All have the same types of adverse
events. OCs may significantly worsen symptoms of lupus. effects. Those with higher doses may be expected to pro-
Mood disorders, including depression, may be worsened duce more adverse effects.
in patients taking OCs. All combination OCs are preg-
nancy category X and are contraindicated in pregnancy. Adverse Effects of Combination
Oral Contraceptives
Drug Interactions: A number of anticonvulsants
(phenobarbital, phenytoin, and carbamazepine) and anti- 70.3 The adverse effects of combined oral
biotics (tetracyclines, rifampin, and ampicillin) can reduce contraceptives are uncommon but may be
the effectiveness of OCs, thus increasing a woman’s risk serious in some women.
of pregnancy. Women who are taking these drugs should
be advised to use additional means of birth control or to The adverse effects of combination OCs have been exten-
have their OC dosages revised. Because OCs can reduce sively studied, and various risk factors have been identi-
the effectiveness of warfarin, heparin, insulin, and certain fied. These are summarized in Table 70.3. For the large
oral antidiabetic drugs, dosage adjustment may be neces- majority of patients, OCs are safe and serious adverse
sary. Protease inhibitors (indicated for human immuno- effects are uncommon. A few of the adverse effects, how-
deficiency virus infection) are contraindicated because ever, may be serious. Because OCs are so widely pre-
they may result in contraceptive failure. Patients who are scribed, nurses should become familiar with the adverse
taking theophylline for asthma or imipramine as an anti- effects and incorporate them into the teaching component
depressant in conjunction with OCs should be evaluated of the treatment plan.
often because these drugs may accumulate to toxic levels
in these individuals. Herbal/Food: OCs have been shown Much of the early research on OCs was performed on
to cause breakthrough bleeding when used concurrently women who were taking high doses of estrogens and pro-
with St. John’s wort. gestins. Most, and perhaps all, of the serious adverse effects
1294 Unit 10 Pharmacology of the Endocrine System
Table 70.3 Adverse Effects Associated with Combination Oral Contraceptives
Adverse Effect Prevention
Breast milk reduction Some studies suggest that OCs may reduce the quantity of breast milk. They should not be taken until 6 weeks
Cancer postpartum.
Glucose elevation Women who test positive for the HPV have an increased risk of cervical cancer. These patients should have
Hypertension regular checkups. Because estrogens promote the growth of certain types of breast cancer, patients with a
Increased appetite, weight gain, fatigue, history of this cancer should not take OCs.
depression, acne, hirsutism
Lupus exacerbation OCs may cause slight increases in blood glucose. Patients with diabetes should monitor their serum glucose
Menstrual irregularities carefully during OC therapy.
Migraines Risk is increased with age, dose, and length of therapy. Blood pressure should be monitored periodically and
Nausea, edema, breast tenderness antihypertensives prescribed as needed.
Teratogenicity
Thromboembolic disorders These are common effects that are often caused by high amounts of progestin. The dose of progestin may need
to be lowered.
Symptoms of systemic lupus erythematosus may worsen in some patients. A progestin-only OC may be an
option for these patients.
Amenorrhea or hypermenorrhea is often caused by low amounts of progestin. The dose of progestin may need to
be increased. Breakthrough bleeding and spotting are common with the low-dose OCs. The patient may need a
higher dose product.
Estrogen may decrease or increase the incidence of migraines. Because migraines are a risk factor for stroke,
patients with migraines should seek advice from their healthcare provider.
These are common effects that are often caused by high amounts of estrogen. The dose of estrogen may need
to be lowered.
Estrogens are pregnancy category X. Patients should be advised to discontinue OCs if pregnancy is confirmed.
Estrogens promote blood clotting. OCs should not be prescribed for patients with a history of thromboembolic
disorders, strokes, or coronary artery disease or for those who are heavy smokers.
of OCs are dose dependent. The newer low-dose formula- About 5% of women who are taking OCs will develop
tions result in far less risk than the original OCs. HTN because the drugs elevate angiotensin and aldoste-
rone levels. Angiotensin is a vasopressor substance
The Centers for Disease Control and Prevention and produced by the kidney, and aldosterone is a hormone
the World Health Organization have developed a compre- secreted by the adrenal cortex of the kidney (see Chapter 31).
hensive list of preexisting medical conditions as absolute The action of both substances can result in HTN. The mean
contraindications for the use of estrogen–progestin con- elevation from high doses of OCs is about 3 to 6 mmHg
traceptives (Curtis et al., 2016). These include current systolic and 2 to 5 mmHg diastolic. Low-dose formulations
breast cancer, severe hepatic disease, major surgery with do not pose a major risk for HTN.
prolonged immobilization, migraines (with aura),
impaired cardiac function, complicated valvular heart OCs can mimic certain symptoms of pregnancy, includ-
disease, HTN (systolic ≥ 160 mmHg or diastolic ≥ 100 ing breast tenderness, nausea, bloating, and chloasma,
mmHg), smoking (age ≥ 35, ≥15 cigarettes/day), history which is a darkened pigmentation found on the forehead,
of stroke, systemic lupus erythematosus (positive or temples, cheeks, and upper lips. If a woman suspects preg-
unknown antiphospholipid antibodies), and high risk for nancy while taking an OC, the drug should be discontin-
thromboembolic disorders. Relative contraindications ued immediately because estrogen and progestin can cause
exist when there are preexisting disorders such as depres- fetal harm.
sion, migraines (without aura), epilepsy, epilepsy therapy
(with certain anticonvulsants), and controlled HTN. The Because estrogen and progesterone can stimulate the
nurse should discuss nonhormonal contraceptive choices growth of some types of cancers, the incidence of cancer in
for women who have serious medical conditions for women taking OCs has been studied for several decades in
which OCs are contraindicated. large numbers of women. Some studies have demonstrated
that long-term use may pose a slightly higher risk of breast
CONNECTION Checkpoint 70.2 cancer, whereas others have shown no relationship. Cervi-
cal cancer is also slightly increased, and this has been
Thromboembolic events are a serious concern for many patients closely associated with human papillomavirus (HPV)
who are taking OCs. From what you learned in Chapter 38, identify infections. The risk of liver cancer may be increased. How-
the classes of drugs that may be used to reduce the risk of thrombo- ever, OCs appear to have protective effects for ovarian and
embolic events in high-risk patients. Answers to Connection Check- endometrial cancers that continue for many years after the
point questions are available on the faculty resources site. Please consult drugs are discontinued. A protective effect has also been
observed for colorectal cancer. Conclusions of these studies
with your instructor.
Chapter 70 Drugs for Modifying Conception 1295
are that women who have a personal or very close family Progestin-only oral contraceptives are taken daily
history of breast cancer should explore nonhormonal throughout the month without the use of placebo tablets.
means of contraception. All women who are taking OCs Minipills are somewhat less effective than estrogen–
should be instructed to perform breast self-examinations, progestin combinations, having a failure rate of 1% to 4%.
as recommended by their healthcare provider, and be Their use also results in a higher incidence of irregular
aware of the importance of routine scheduling of mammo- menstrual cycles, including amenorrhea, prolonged bleed-
grams as appropriate for their age range. ing, or breakthrough spotting. Menstrual irregularity is the
most frequently reported adverse effect. The risk of ectopic
Other conditions associated with OCs are abnormal pregnancy is higher with progestin-only products.
uterine bleeding, benign hepatic adenoma, multiple births, Progestin-only PO drugs are generally reserved for patients
retinal disorders, and melanoderma. These conditions, who are at high risk for estrogen-related adverse effects or
though rare, have been reported and they normally resolve who are lactating. Unlike estrogens, progestins are not
after discontinuing the use of OCs. OCs may accelerate the associated with a higher risk of thromboembolic events,
formation of gallstones in patients who have preexisting and they do not have any effect on breast cancer. The
gallbladder disease. The drugs may increase glucose levels progestin-only products are pregnancy category X.
and suppress insulin responsiveness, although this can be
prevented by adjustments in the insulin dose of patients Products that contain norethindrone only include
with diabetes. Aygestin, Camila, Errin, Jolivette, Nora-BE, and Ortho
Micronor. In addition to contraception, norethindrone
Although not an adverse effect, healthcare providers therapy is approved to treat amenorrhea, dysfunctional
and their patients should be aware that some studies have uterine bleeding, and endometriosis. The doses used for
indicated that the combined hormonal patch and oral levo- contraception are only 0.35 mg/day, whereas those for
norgestrel emergency contraception may have lower rates uterine conditions are 2.5 to 10 mg/day. Detailed informa-
of effectiveness in women who are obese (Simmons & Edel- tion on the contraindications, drug interactions, and
man, 2016). The correlation between effectiveness and adverse effects of progestins are included in Chapter 69,
weight (or BMI) is an ongoing area of research. along with a prototype feature for medroxyprogesterone
(Depo-Provera, Depot-SubQ-Provera, Provera).
When discussing the risks and benefits of hormonal
contraception with patients, the nurse should place the Long-Acting Reversible
drug in context with the health risks associated with preg- Contraceptives
nancy and delivery. Many patients do not understand that
pregnancy itself may cause many challenging health condi- 70.5 Long-acting contraceptives and novel
tions for the mother. Pregnancy-related mortality in the delivery methods offer women additional birth
United States averages 16 deaths per 100,000 live births, control choices.
with non-Hispanic black women having the highest inci-
dence of death (Creanga et al., 2015). Maternal morbidity Delivery methods have been developed that are able to
includes conditions such as hemorrhages, preeclampsia or provide long-acting reversible contraception for periods
eclampsia, obstetric trauma, infections, gestational diabe- lasting from weeks to years. The long-acting reversible
tes, and HTN. Placed in the proper context, the risks of contraceptives (LARCs) and novel delivery systems were
pregnancy for most patients (those without absolute con- developed to offer ease of use and improve adherence.
traindications for OC use) are likely as great, or greater, They vary in efficacy, reversibility, and discreteness of use.
than hormonal contraception.
Transdermal patch: Transdermal hormonal contracep-
Progestin-Only Oral tion is a safe, effective, and easy-to-use birth control
Contraceptives method. Approved in 2001, Ortho-Evra is a topical patch
worn on the skin of the buttock, arms, or trunk that con-
70.4 Oral contraceptives that contain only tains ethinyl estradiol and norelgestromin. The patch
progestin are often used when estrogen is slowly releases the hormones, which penetrate the skin
contraindicated. and are distributed throughout the body. The patch is
changed every 7 days for the first 3 weeks, followed by a
Although most OCs use a combination of estrogen and patch-free week 4 (days 22–28). The patch may be worn
progestin, a few products contain only progestin. The during bathing, exercise, and other daily activities. Should
progestin-only OCs, sometimes called minipills, are less the patch fall off, which occurs in about 5% of the applica-
effective at preventing ovulation. They prevent pregnancy tions, it should be replaced as soon as possible. The serum
primarily by causing a thick, viscous cervical mucus at the estrogen levels of patients who use the patch are 60%
entrance to the uterus that discourages sperm penetration.
They also tend to inhibit implantation of a fertilized egg.
1296 Unit 10 Pharmacology of the Endocrine System
CONNECTIONS: Preparing for Advanced Practice
Contraceptive Choices
Case Discussion
Lauren, a 33-year-old mother of four, is married and is looking Deciding on the right method of birth control is very personal
for a reliable method of birth control. When asked about her and is a common reason women seek gynecologic care. Using
plans for more children, she states that she is not interested in the birth control patch is safe, simple, and convenient. Lauren’s
having another child right now but may want another child in the ability to become pregnant will return quickly when use of the
future. She insists on a contraceptive method other than con- patch is stopped, and because the patch works like the pill, it
doms because her husband doesn’t like using them. She was increases adherence for women who are concerned about for-
taking “the pill” for a while, but had a difficult time remembering getting to take a pill every day.
to take a pill every day and she would miss several days at a
time. You conduct some basic screening and obtain the follow- Lauren’s BMI was within normal range. However, if it were
ing information: blood pressure, 126/82 mmHg; pulse, 62 beats/ above the normal range or she weighed over 90 kg (198 lb), the
min; and respiratory rate, 16 breaths/min; she does not smoke transdermal patch would not be a good option. Research shows
or drink and denies drug use. Her body mass index (BMI) is 22 that the transdermal patch is less effective in women who are
(normal weight). You determine she is a candidate for a trans- obese.
dermal patch and after discussion about potential risks and
adverse effects, she is started on Ortho-Evra and is taught how Healthcare providers should offer patients an additional pre-
to use it. Is this an appropriate birth control option for Lauren? scription for the contraceptive patch in case of detachment. The
drug is mixed with the adhesive and, therefore, patches that do not
stick must be replaced to maintain therapeutic levels of hormone.
higher compared to those of patients who take combina- frequently because it may fall out. Adverse effects include
tion OCs. Used patches still contain significant hormone nausea, bloating, headaches, breast tenderness, and
levels and must be discarded in a waste container away breakthrough bleeding. If the ring is expelled from the
from children and pets. They should not be flushed down vagina, it may be rinsed with water and replaced. Local
the toilet because residual estrogen can pollute wastewa- effects may include vaginal irritation, sensation of a for-
ter, lakes, and streams. eign body, and vaginitis. The NuvaRing should be dis-
carded in a waste container away from children and not
Adverse effects and contraindications are the same as flushed down the toilet.
those for OCs. Some research suggests that patients using
the patch have an increased risk of venous thromboembo- Depot injection methods: Intramuscular (IM) medroxy-
lism (VTE) compared to women taking OCs. In response to progesterone acetate (Depo-Provera) was approved for
this research, the FDA created a black box warning for contraceptive use in the United States in 2004. A single
Ortho-Evra that women with a history of blood clots should deep IM injection provides 3 months of contraceptive pro-
discuss other means of contraception with their healthcare tection. The same drug may be injected subcutaneously
provider. (Depo-SubQ-Provera) with the same duration of action and
effectiveness. Medroxyprogesterone suppresses ovulation,
Vaginal ring: The NuvaRing, illustrated in Figure 70.2, is inhibits sperm from reaching the egg by thickening the cer-
a flexible, soft vaginal ring impregnated with a low-dose, vical mucus, and prevents a fertilized egg from implanting
sustained release, combined hormonal contraceptive. It is in the uterus. Neither depot delivery method contains
approximately 5 to 7.5 cm (2–3 in.) in diameter and contains estrogen. The drug is usually given on days 1 through 5 of
ethinyl estradiol and etonogestrel. The ring is inserted into the menstrual cycle. The depot injection methods are very
the vagina once a month to provide 3 weeks of contracep- effective at preventing pregnancy.
tive protection. The ring slowly releases the hormones,
which are absorbed across the vaginal mucosa into the Once injected the actions of the drug cannot be reversed
blood and distributed throughout the body. The contracep- and fertility may not be restored for up to 12 months after
tive action is systemic in nature and not localized to the discontinuation. The most common adverse effects are
vagina. The ring is removed at the end of week 3, and a new menstrual disturbances, headache, acne, injection-site reac-
ring is inserted a week later. If forgotten and left in place for tions, weight gain, and decreased libido. This drug carries
more than 3 weeks, contraceptive action may be lost. a black box warning that long-term use causes significant
loss of bone mineral density. This drug is pregnancy cate-
The main adverse effects of the NuvaRing are similar gory X. Medroxyprogesterone is also approved to treat
to those of combination OCs. Women sometimes discon- inoperable endometrial and renal cell carcinomas and men-
tinue using the vaginal delivery method due to discom- strual disturbances. A prototype feature for medroxypro-
fort of the device during intercourse. Women who are gesterone may be found in Chapter 69.
experiencing uterine prolapse must monitor the ring
Chapter 70 Drugs for Modifying Conception 1297
Uterus
Vagina
NuvaRing
C (b)
Figure 70.2 Vaginal medication administration: (a) The NuvaRing® contraceptive; (b) proper insertion of the NuvaRing.
Subdermal implant: Although several contraceptive sub- thickening of the endometrium and increased cervical
dermal implants have been approved since 1996, only Nex- mucus that slows down sperm motility. The most common
planon is available. Formerly called Implanon, the implant adverse effects include uterine and vaginal bleeding, dys-
consists of a single plastic tube about the size of a matchstick, menorrhea, intermenstrual bleeding and spotting, abdomi-
containing 68 mg of the progestin etonogestrel. Inserted on nal and pelvic pain, and ovarian cysts.
the inner side of the upper arm, the device releases the pro-
gestin slowly, for up to 3 years. Although the device can be The oldest product, ParaGard, is a plastic device that is
readily removed, some women may experience pain, inflam- partially covered with copper. It is believed that the copper
mation, or hematoma at the removal site. Other adverse triggers a spermicidal-like reaction in the body that slows
effects are the same as those of other progestins. sperm motility and prevents the sperm from reaching the
ovum. If fertilization does occur, implantation is not likely
Intrauterine devices: Intrauterine devices (IUDs) are to happen because the copper causes endometrial changes
LARCs designed in a T shape that are safe, inexpensive, to make the lining less favorable. It can be left in place for
and reliable methods of contraception. They are placed by up to 10 years, and the main adverse effects are bleeding
the healthcare provider and offer a major advantage for between menses, dysmenorrhea, and expulsion of the
women who are likely to forget a daily pill or who prefer device. ParaGard is an effective, nonhormonal option for
greater ease of use. Unlike OCs, these devices have no effect patients who have contraindications to using estrogen or
on ovulation. The IUD is not felt by the woman or her part- progesterone.
ner during intercourse and it can be removed at any time.
Fertility returns quickly after removal of the device. PharmFACT
Liletta, Mirena, Kyleena, and Skyla are called hor- The use of long-acting reversible contraception has increased
monal IUDs because they contain levonorgestrel that is markedly in recent years. From 2002 to 2013, the use of
released very slowly to prevent conception for 3 to 6 years, intrauterine devices increased 83% and the use of subdermal
depending on the product. Contraception results from a hormonal implants tripled (Branum & Jones, 2015).
1298 Unit 10 Pharmacology of the Endocrine System
PROTOTYPE DRUG Nonoxynol-9
Classification Therapeutic: Intravaginal contraceptive
Pharmacologic: Spermicide
Therapeutic Effects and Uses: Originally approved
in 1963, nonoxynol-9 is a topical contraceptive that acts
by inhibiting the ability of sperm to reach the ovum.
Most products have a duration of spermicidal action of
60 minutes; the contraceptive sponge provides 24 hours of
protection.
Figure 70.3 The contraceptive sponge is moistened well with Pharmacokinetics: Nonoxynol-9 disrupts the cell
water and inserted into the vagina with the concave portion membrane of sperm, causing it to lose motility and func-
positioned over the cervix. tion. The carrier (foam, sponge, cream, etc.) may also act as
a physical barrier to sperm motility.
Spermicides
Route(s) Apply or insert vaginally
70.6 Spermicides are safe but should be Absorption
combined with barrier protection for maximum Distribution Minimal absorption
effectiveness.
Primary metabolism Acts locally, killing the sperm on
Spermicides are drugs that kill sperm. They come in a Primary excretion contact
variety of creams, foams, jellies, and suppositories that
immobilize or destroy sperm when inserted into the Onset of action Not metabolized
vagina prior to intercourse. Spermicides are available over
the counter (OTC). Duration of action Small amounts by the kidneys
and in feces
To be effective, spermicides must be applied high into
the vagina, as close to the cervix as possible, approximately Immediate for creams, foams,
20 minutes before intercourse. Most spermicides have a gels, and sponge; 5–15 min for
duration of action of only 1 hour and must be reapplied if suppositories
coitus extends beyond this time.
Up to 24 h after intercourse
The contraceptive sponge, which is illustrated in (sponge)
Figure 70.3, is soft and absorbent and contains nonoxynol-9.
The sponge is moistened with water to activate the spermi- Adverse Effects: Adverse effects are uncommon. Vagi-
cides and inserted into the vagina to cover the cervix. The nal irritation and dryness, increase in vaginal infections,
sponge releases the drug slowly and may provide up to toxic shock syndrome, and irritation of the genitalia of the
24 hours of contraceptive protection. It is left in place for sexual partner have been reported.
6 hours after intercourse but must be removed by 30 hours
after insertion. The sponge delivery system has the same Contraindications/Precautions: Women with cys-
effectiveness as spermicidal gels, creams, and suppositories. tocele, prolapsed uterus, sensitivity or allergy to non-
Adverse effects include local irritation and vaginal dryness. oxynol-9, vaginitis, or toxic shock syndrome, or those
who are pregnant, postabortion, or postpregnancy should
Patients should be informed that spermicides have low avoid this drug.
levels of effectiveness when used alone and should there-
fore be used in conjunction with barrier methods such as Drug Interactions: Intravaginal azole antifungals may
condoms and diaphragms. Nonoxynol-9 does not offer any inactivate the spermicides.
protection against chlamydia, gonorrhea, or the human
immunodeficiency virus (HIV). In fact, frequent use of Pregnancy: Category C.
spermicides disrupts the vaginal epithelium and may actu- Treatment of Overdose: Overdose is not likely.
ally increase the risk of HIV transmission from an infected
partner. Patients must be instructed to take added precau- Nursing Responsibilities:
tions to prevent such transmissions.
• Monitor for signs of vaginal infection or irritation.
Patient and Family Education:
• Be aware that spermicides should be used in conjunc-
tion with barrier methods such as condoms or
diaphragms.
• Be aware that this drug does not protect against the
transmission of HIV or sexually transmitted infections.
• Discontinue nonoxynol-9 if pregnancy is suspected.
Chapter 70 Drugs for Modifying Conception 1299
CONNECTIONS: NURSING PRACTICE APPLICATION
Patients Receiving Hormonal Contraceptives
Assessment
Baseline assessment prior to administration:
• Obtain a complete health history including cardiovascular, peripheral vascular, migraines, thyroid, hepatic, or kidney disease; diabetes; pregnancy; or
breastfeeding. Note personal or family history of thromboembolic disorders (e.g., MI, stroke, peripheral vascular disease) and of reproductive cancers
(e.g., breast, uterine, or ovarian cancer).
• Obtain a drug history including allergies, current prescription and OTC drugs, herbal preparations, alcohol use, and smoking. Be alert to possible drug
interactions.
• Evaluate appropriate laboratory findings (e.g., complete blood count [CBC], platelets, electrolytes, glucose, lipid, and thyroid function levels), Pap test,
HPV screening, and pregnancy test.
• Obtain baseline height, weight, and vital signs.
• Assess the patient’s ability to receive and understand instructions. Include family and caregivers as needed.
Assessment throughout administration:
• Assess for desired therapeutic effects dependent on the reason the drug is given (e.g., pregnancy prevention).
• Continue periodic monitoring of CBC, platelets, thyroid function, and glucose.
• Monitor vital signs and weight at each healthcare visit.
• Assess for adverse effects: nausea, vomiting, headache, weight gain, breast tenderness, skin rash, acne, fluid retention, changes in mood, or midcycle
breakthrough bleeding. Immediately report tachycardia, palpitations, HTN, severe headache, cramping in calves, chest pain, or dyspnea.
Implementation
Interventions and (Rationales) Patient-Centered Care
Ensuring therapeutic effects:
• Monitor appropriate medication administration for optimal results. • Instruct the patient to take the pill at the same time daily to help with
remembering to take it. Do not omit, increase, or decrease doses with-
(OCs are nearly 100% effective when taken as required. Skipping out consulting the healthcare provider. Omitting or decreasing doses
doses increases the risk of pregnancy. Transdermal patches, depot increases the chance of pregnancy; increasing doses may increase the
injections, or IUDs may be desirable for women who experience risk of adverse effects.
difficulty adhering to OCs or for those who choose not to take daily
medication.) • Encourage women to discuss LARCs with their healthcare provider as
Minimizing adverse effects: appropriate.
• Monitor for symptoms of cardiopulmonary, cerebrovascular, and
peripheral vascular thromboembolism. Monitor blood pressure at • Instruct the patient to immediately report:
each clinical visit. (Thromboembolic events are a possible adverse • Dyspnea, chest pain, or blood in sputum (possible pulmonary embolism)
effect of OC drugs. The risk increases in women with a previous • Heaviness, chest pain, or overwhelming feeling of fatigue and weak-
history of cardiovascular disease, women classified as obese, and ness accompanied by nausea and diaphoresis (possible MI)
in women who smoke. Monitor for symptoms of peripheral throm- • Sudden, severe headache, especially if associated with a prehead-
bophlebitis, pulmonary embolism, MI, stroke, or other complications ache aura, dizziness, difficulty with speech, numbness in an arm or
related to blood clots.) leg, or difficulty with vision (possible stroke)
• Eye problems such as blurred vision or loss of vision (possible
• Encourage smoking cessation and provide information about smoking stroke, retinal hemorrhage or thrombus)
cessation programs. (Smoking greatly increases the risk of experienc- • Warmth, redness, swelling, or tenderness in calf, or pain on walking
ing the adverse effects of hormone therapy.) (possible thrombophlebitis).
• Teach the patient to monitor blood pressure periodically and report
• Monitor Pap tests, HPV screening, and breast examinations as any blood pressure above 140/90 mmHg or per parameters as
ordered. (Pap tests and breast examinations, including mammography ordered by the healthcare provider.
as appropriate, will monitor for the development of breast tumors or
cervical cancer.) • Advise the patient of the risk of smoking while using OCs; discuss and
provide literature on smoking cessation programs, providing referral to
• Monitor the occurrence of any breakthrough bleeding. Report any appropriate support groups.
continuous, unusual, or heavy bleeding. (Spotting may occur, espe-
cially with low-dose hormone therapy, at midcycle. Any continuous, • Teach the patient how to perform breast self-examinations, but monthly
unusual, or heavy bleeding may indicate adverse effects, pregnancy examinations may not be recommended by the healthcare provider
loss, or disease and should be reported.) except for women at high risk for breast cancer. For women over age
40, advise the patient on the need for follow-up mammography as per
• Monitor hepatic function tests and symptoms of liver dysfunction, the healthcare provider recommendations.
lipid profile studies, and thyroid levels periodically. (OCs are associ-
ated with an increased risk of gallbladder disease and a rare risk of • Advise the patient on the need for regularly scheduled gynecologic
hepatotoxicity.) examinations to ensure continued health.
• Monitor concurrent drug therapy and any new prescriptions received. • Teach the patient that spotting may occur midcycle while on OCs but
(Many drugs decrease or alter the effectiveness of OCs including to report any unusual changes in the amount or if the bleeding contin-
drugs in the penicillin, tetracycline, barbiturate, antiseizure, antidepres- ues.
sant, and benzodiazepine classifications.)
• Instruct the patient to return periodically for laboratory tests.
• Teach the patient to report any symptoms of abdominal or right upper
quadrant discomfort or pain, yellowing of the skin or sclera, fatigue,
anorexia, darkened urine, or clay-colored stools. Report any severe
abdominal pain immediately.
• Teach the patient to advise all healthcare providers of the use of OCs
before beginning any new prescription.
(continued )
1300 Unit 10 Pharmacology of the Endocrine System
CONNECTIONS: NURSING PRACTICE APPLICATION (continued)
Implementation
Interventions and (Rationales) Patient-Centered Care
Patient understanding of drug therapy: • The patient should be able to state the reason for the drug, appropriate
• Use opportunities during administration of medications and during dose and scheduling, what adverse effects to observe for, and when to
report them.
assessments to discuss the rationale for drug therapy, desired thera-
peutic outcomes, commonly observed adverse effects, parameters
for when to call the healthcare provider, and any necessary monitoring
or precautions. (Using time during nursing care helps to optimize and
reinforce key teaching areas.)
Patient self-administration of drug therapy: • Teach the patient to take the pill at the same time daily to help with
• When administering the medication, instruct the patient in proper self- remembering to take it. If a dose is missed, take the drug as follows:
• For estrogen–progestin combination OCs: If a dose is missed, take
administration of the drug, e.g., consistently at the same time each it as soon as it is remembered, and take the next pill at its normally
day to help with remembering to take the dose, followed by teach- scheduled time. If two consecutive doses are missed, take 2 tablets
back. (Utilizing time during nurse administration of these drugs helps on both the day the missed doses are remembered and on the
to reinforce teaching.) following day. Follow the remaining schedule of pills, but a second
method of contraception (e.g., a barrier method) should be used
for at least 7 days after restarting the pills. If 3 or more consecutive
days are missed, use another form of contraception until the pills
can be restarted in the next monthly cycle.
• For progestin-only OCs: If a dose is missed, take the pill as soon as
remembered, but use an additional form of contraception until the
next cycle of pills is started.
• Transdermal patches (e.g., Ortho-Evra) and vaginal rings (e.g.,
NuvaRing): Patches and rings are changed weekly for 3 weeks,
followed by 1 week of being patch- or ring-free. If the patch falls off
or the ring falls out, it should be replaced with a new patch or ring.
Safely discard used patches or rings in the trash.
• Carefully follow the instructions on the label for apply- these occur due to the inconsistent use or failure of contra-
ing the drug, or use as directed by the healthcare pro- ceptive devices. EC, commonly referred to as the “morning
vider. If excessive burning, stinging, or irritation occurs, after pill,” offers a means of protecting against unwanted
try a product with a lower strength of nonoxynol-9. pregnancies.
• If using a diaphragm, place 1 to 3 tsp of the spermicide The treatment goal for these patients is to provide
in the dome prior to insertion. effective and immediate contraception. EC must be taken
as soon as possible after intercourse. When used accord-
• Leave the spermicide and diaphragm in place 6 hours ingly, these drugs act by preventing ovulation; they do not
after intercourse. cause abortion. If implantation of an embryo has already
occurred, the drugs used for EC will have no effect on the
• Use the spermicide before the first and every subse- established pregnancy. Two different medications are
quent act of intercourse. approved for EC: Plan B and ulipristal (Ella). Table 70.4 lists
drugs, routes, and dosages for EC. These drugs are not
• Report burning; inflammation; intense vaginal and intended to replace regular methods of contraception.
vulvar itching; cheesy, curd-like discharge; painful
intercourse; and dysuria to the healthcare provider. Plan B is approved for OTC purchase without age
restriction. Plan B has largely been replaced by Plan B One
Drugs Similar to Nonoxynol-9 Step, which offers the convenience of a single 1.5-mg dose.
There are no drugs that are similar to nonoxynol-9. The active drug in Plan B is levonorgestrel, which is the
same progestin used for contraception in some IUDs (see
Emergency Contraception Section 70.5). There is, however, a large difference in doses.
Whereas the long-acting Mirena releases 20 mcg/day of
70.7 Emergency contraception provides a levonorgestrel over a 5-year period, Plan B delivers a total
reproductive option for women who have of 1500 mcg of levonorgestrel in a single day. The drug is
unprotected sex or contraceptive failure. most effective when taken either within 72 hours (Plan B) or
120 hours (Plan B One Step) after unprotected intercourse.
Emergency contraception (EC) is the prevention of
implantation following unprotected intercourse or contra- Plan B is not 100% effective. The normal rate of preg-
ceptive failure. Statistics suggest that almost half the preg- nancy from a single unprotected sex act is 8%; Plan B is
nancies in the United States are unplanned and some of estimated to lower this risk to 1% to 2%. Serious adverse
Chapter 70 Drugs for Modifying Conception 1301
Table 70.4 Drugs for Emergency Contraception and Pharmacologic Abortion
Drug Route and Adult Dose (Maximum Dose Where Indicated) Adverse Effects
Drugs for Emergency Contraception Nausea, heavy menstrual bleeding, lower abdominal
pain, headache, fatigue, and dizziness
levonorgestrel (Plan B, PO (Plan B): 1 tablet within 72 h of intercourse followed by 1 tablet Serious adverse effects are rare when only 1 or
Plan B One Step) 12 h later (0.75 mg in each pill) 2 doses are administered
Headache, abdominal pain, nausea, dysmenorrhea,
PO (Plan B One Step): 1 tablet (1.5 mg) within 120 h of intercourse fatigue, dizziness
ulipristal (Ella) PO: 1 tablet (30 mg) within 5 days of unprotected intercourse or
contraceptive failure
Drugs for Pharmacologic Abortion Serious adverse effects are rare when only 1 dose is
administered
carboprost (Hemabate) IM (initial): 250 mcg (1 mL) repeated at 0.5- to 3.5-h intervals if
indicated by uterine response. Dosage may be increased to 500 mcg Nausea, vomiting, cramping, diarrhea, fever
(2 mL) if uterine contractility is inadequate after several doses of Uterine laceration, rupture, or hemorrhage
250 mcg (1 mL), not to exceed a total dose of 12 mg or continuous
administration for 1 month Nausea, vomiting, cramping, diarrhea, fever
Uterine laceration, rupture, or hemorrhage
dinoprostone (Cervidil, Intravaginal: Insert 20-mg suppository high in the vagina; repeat Nausea, vomiting, diarrhea
Prepidil, Prostin E2) q2–5h until abortion occurs or membranes rupture (max: total dose Abdominal pain, headache, uterine hemorrhage,
240 mg) respiratory arrest
Nausea, vomiting, diarrhea
methotrexate with IM methotrexate (50 mg/m2) followed 5 days later by intravaginal Abdominal pain, headache, uterine hemorrhage
misoprostol 800 mcg of misoprostol
mifepristone (Mifeprex) with PO: 200 mg of mifepristone on first day, followed 24–48 h later with
misoprostol 800 mcg of misoprostol
Note: Italics indicate common adverse effects. Underline indicates serious adverse effects.
effects with Plan B are uncommon. Nausea and vomiting One option for the patient may be a medical abortion.
are the most common adverse effects, and abdominal pain, Pharmacologic (medical) abortion is the removal of an
fatigue, headache, irregular (increased or decreased) men- embryo by the use of drugs after implantation has occurred.
strual bleeding, and dizziness are reported by a number of Drugs used to induce abortion are called abortifacients.
patients. Fertility returns quickly after taking Plan B; there-
fore, the patient should be encouraged to implement rou- Once the ovum has been fertilized, several drugs are
tine contraception measures as soon as possible. available to terminate the pregnancy, as listed in Table 70.4.
A single dose of mifepristone (Mifeprex) followed 24 to
In 2010, ulipristal (Ella) was approved as a single-dose 48 hours later by a single dose of misoprostol is a frequently
product for EC. This drug is a mixed progesterone agonist– used regimen. Although the mifepristone–misoprostol
antagonist that acts by preventing ovulation. Unlike Plan combination should never be used as a substitute for an
B, which is available OTC, ulipristal requires a prescrip- effective means of contraception, these drugs do offer
tion. One advantage of ulipristal is that it retains its effec- women a safer alternative than surgical abortion. The
tiveness for 5 days following unprotected sex. actions of the two drugs are as follows:
Drugs for Pharmacologic Abortion • Mifepristone acts by blocking progesterone receptors,
resulting in softening and dilation of the cervix and
70.8 Abortifacients are drugs that are used to degeneration of the uterine endometrium. If given
terminate pregnancy. within 3 days of intercourse, mifepristone alone is
almost 100% effective at preventing pregnancy. Given
A woman who is in early pregnancy may decide that she is up to 9 weeks after conception, mifepristone aborts
no longer able to carry the child to term. In some pregnan- the implanted embryo.
cies, major abnormalities may be identified in the fetus
that would prevent it from reaching term. The nurse • Misoprostol is a prostaglandin that induces strong
should use his or her knowledge of the stages of fetal uterine contractions, thus increasing the effectiveness
growth and development to counsel the patient regarding of the pharmacologic abortion.
the risks and benefits of available options. The nurse must,
however, be aware of applicable state laws and regulations Pharmacologic abortion must be conducted under the
that restrict certain treatments. close supervision of a healthcare provider. The patient is
often required to sign consent forms after it has been deter-
mined that the pregnancy is under 49 days. The patient
1302 Unit 10 Pharmacology of the Endocrine System
receives an assessment by the healthcare provider 2 days Because rare instances of uterine laceration and rupture
after dosing. If abortion has not occurred, additional miso- have been reported, the patient is monitored closely for
prostol may be administered and the patient returns to the uterine activity, excessive pain, and vaginal bleeding. Indi-
healthcare provider in 14 days to confirm that abortion is cations for the prostaglandins are given in Table 70.5.
complete. Occasionally pharmacologic abortion does not
occur and the patient is referred for surgical abortion. The PROTOTYPE DRUG Mifepristone (Mifeprex)
primary adverse effect of mifepristone–misoprostol is
cramping that occurs soon after taking misoprostol. Nausea Classification Therapeutic: Drug for abortion
is common. The most serious adverse effect is prolonged Pharmacologic: Abortifacient,
bleeding, which may continue for 1 to 2 weeks after dosing.
progesterone antagonist
Methotrexate, an antineoplastic drug, is sometimes
combined with intravaginal misoprostol. Methotrexate Therapeutic Effects and Uses: Approved in 2000,
50 mg/m2 is given IM, followed in 5 days by 800 mcg of mifepristone was originally indicated for terminating
intravaginal misoprostol. If abortion does not occur within pregnancies of less than 49 days gestation, but this was
24 hours, the misoprostol is repeated. The treatment is 96% expanded to 70 days in 2016. Due to the controversial
effective at causing abortion. Most patients experience nature of this drug, distribution is restricted and tightly
adverse effects such as nausea, vomiting, diarrhea, head- controlled. It is not available in pharmacies and is sold
ache, dizziness, abdominal cramping, and hot flashes. directly to approved, registered prescribers. Surgical inter-
vention must be readily available in case of incomplete
Prostaglandins may also be used to induce abortion. abortion, severe bleeding, or other serious complications.
Prostaglandins are natural hormones that produce a As revised by the FDA in 2016, pharmacotherapy with
diverse number of local actions in virtually every body sys- mifepristone requires one 200-mg tablet of mifepristone
tem. In the uterus, the normal function of prostaglandins is followed 24 to 48 hours later by 800 mcg of misoprostol
to cause contraction of smooth muscle. They serve a valu- taken by the buccal route. Patients must return to their
able function in inducing contractions at the beginning of healthcare provider between 7 and 14 days to assess
labor and in promoting cervical ripening. whether pregnancy termination has occurred.
The three approved prostaglandins include dinopros- Mifepristone may be used off-label as a means of EC.
tone (Cervidil, Prepidil, Prostin E2), carboprost (Hemabate), Given as a single 600-mg dose, it has the same effectiveness
and misoprostol. All three may be used to induce uterine and safety profile as Plan B. Other off-label indications
contractions that can expel an implanted embryo and result include breast cancer, endometriosis, uterine leiomyomata,
in abortion up to the second trimester. Dinoprostone is used Cushing’s syndrome, and termination of ectopic pregnancy
early in pregnancy and comes in preparations of vaginal (in combination with methotrexate).
suppositories (Prostin E), vaginal inserts (Cervidil), and gel,
which are inserted high into the vaginal canal. Carboprost is Mechanism of Action: Mifepristone is a strong
administered by deep IM injection and misoprostol by tab- antagonist of progesterone and corticosteroids. This drug
let. When used for abortion, misoprostol is administered blocks the supportive effects of progesterone on the uter-
with either mifepristone or methotrexate. Nausea, vomit- ine lining. If given within 72 hours of intercourse, a fer-
ing, and diarrhea are common adverse effects of prostaglan- tilized ovum will not be able to implant in the uterus.
dins and uterine cramping is expected. Drug-induced fever During early pregnancy, mifepristone acts by increasing
occurs in the majority of patients and may last up to 6 hours. the synthesis of prostaglandins and sensitizing the uterus
Table 70.5 Indications for Prostaglandins
INDICATIONS
Control of Cervical Labor
Postpartum Bleeding
Drug Abortifacient Ripening Induction Induction Other
A A
carboprost (Hemabate) OO Hemorrhagic cystitis (O);
prostaglandin F2 A — hydatidiform mole (O)
dinoprostone (Cervidil, Prepidil, A— Hydatidiform mole (A)
Prostin E2) prostaglandin E2 O O
misoprostol prostaglandin E1 OO Nonsteroidal anti-inflammatory
drug–induced ulcer prophylaxis
(A); kidney transplant rejection
prophylaxis (O)
Note: A 5 FDA-approved indication; O 5 off-label indication.
Chapter 70 Drugs for Modifying Conception 1303
to the effects of prostaglandins. When misoprostol (a pros- metabolism of mifepristone and lowering its serum levels.
taglandin) is given 24 to 48 hours after mifepristone, the Herbal/Food: St. John’s wort and grapefruit juice may
prostaglandin increases uterine contractions, which aids in decrease serum levels of mifepristone.
expelling the embryo from the uterus.
Pregnancy: Category X.
Pharmacokinetics:
Treatment of Overdose: Overdose has rarely
Route(s) PO occurred with mifepristone. Treatment is supportive.
Absorption Rapidly absorbed Nursing Responsibilities:
Distribution Crosses the placenta; it is un- • Conduct a comprehensive health assessment, includ-
ing the patient’s ability to understand the conse-
known if secreted in breast milk; quences of drug therapy and her ability to comply
with the regimen.
98% bound to plasma protein
• Confirm a positive pregnancy test and that the length
Primary metabolism Hepatic (CYP3A4) of gestation is less than 9 weeks.
Primary excretion Mostly feces, small amounts in • Ensure that the proper emergency medical support is
available in case of partial abortion or excessive
urine bleeding.
Onset of action Rapid • Assess the patient’s medical history for the presence of
an IUD, use of anticoagulants, presence of bleeding
Duration of action Half-life: 18 h disorders, or corticosteroid therapy.
Adverse Effects: Nearly all patients who take the • Instruct the patient on the expected adverse effects,
mifepristone–misoprostol combination experience adverse especially cramping, and that vaginal bleeding may
effects. The most frequent adverse effects of mifepristone continue for several weeks to a month.
are headache, dizziness, nausea, vomiting, fatigue, and
abdominal pain or cramping. Vaginal bleeding and spot- • Instruct the patient on steps to take in case of emer-
ting will occur for about 16 days. Black Box Warning: Seri- gency, including the phone number and address of the
ous and sometimes fatal infections and prolonged heavy nearest emergency center.
bleeding have occurred. Excessive or prolonged bleeding
may be a sign of incomplete abortion and prompt medi- Lifespan and Diversity Considerations:
cal intervention is required. Rare cases of septic shock have
been reported. • Because mifepristone is metabolized through the
CYP450 metabolic pathways, monitor ethnically
Contraindications/Precautions: Because mifepris- diverse populations more frequently to ensure opti-
tone is a corticosteroid antagonist, its use in patients mal therapeutic effects and minimize adverse effects.
who are taking long-term corticosteroid therapy or
who have chronic adrenal failure is contraindicated. Patient and Family Education:
The mifepristone–misoprostol combination is contra-
indicated in patients with ectopic pregnancy because • Follow the therapeutic regimen exactly as prescribed
the therapy will be ineffective. Those on anticoagulant by the healthcare provider.
therapy or who otherwise have an increased risk for
bleeding should not receive mifepristone. Patients with • Attend all follow-up appointments because these are
an IUD in place should have the device removed before essential for safe and effective drug therapy.
mifepristone is administered. The drug is contraindi-
cated for use in patients who are unable to understand • Immediately report heavy vaginal bleeding (use of
the implications of abortion or who may not comply more than two thick sanitary pads per hour for 2 con-
with the established regimen. Safety in patients under secutive hours), persistent vomiting, severe abdomi-
age 18 has not been established. When administered for nal cramps, fever of 38°C (100.4°F) or higher, or
nonabortion indications, this drug is contraindicated in weakness to the healthcare provider.
pregnancy (category X).
• Do not take any other prescription or nonprescription
Drug Interactions: Because mifepristone is taken drugs, dietary supplements, or herbal products with-
in only one or two doses, serious drug interactions are out approval of the healthcare provider.
unlikely. This drug does, however, have an extended half-
life that may cause interactions after it is discontinued. • Resume or initiate birth control immediately after
Mifepristone is metabolized by hepatic CYP450 enzymes the treatment ends or as directed by the healthcare
and may interact with drugs that induce or inhibit this provider.
enzyme system. For example, phenytoin, phenobarbi-
tal, and carbamazepine induce CYP3A4, increasing the Drugs Similar to Mifepristone (Mifeprex)
There are no drugs that are similar to mifepristone.
1304 Unit 10 Pharmacology of the Endocrine System
Understanding Chapter 70
Key Concepts Summary 70.5 Long-acting contraceptives and novel delivery
methods offer women additional birth control
70.1 Selection of a contraceptive is based on choices.
effectiveness, safety, and personal choice.
70.6 Spermicides are safe but should be combined with
70.2 The most effective oral contraceptives include barrier protection for maximum effectiveness.
combinations of low-dose estrogens and progestins.
70.7 Emergency contraception provides a reproductive
70.3 The adverse effects of combination oral option for women who have unprotected sex or
contraceptives are uncommon but may be serious contraceptive failure.
in some women.
70.8 Abortifacients are drugs that are used to terminate
70.4 Oral contraceptives that contain only progestin are pregnancy.
often used when estrogen is contraindicated.
CASE STUDY: Making the Patient Connection
Remember the patient weight is 62.6 kg (138 lb) and her height is 1.7 m (5 ft 7 in.).
“Lila Bastian” from the Her skin is dry and warm to the touch, mucous membranes
beginning of the chapter? are pink and moist, and there are no outward signs of dis-
Now read the remainder tress. Her abdomen is soft and not tender, and there are no
of the case study. Based signs of bloating or distention. She has no vaginal bleeding
on the information pre- at this time. Lila emphasizes that she only had sex once,
sented within this chap- 2 days ago. A urine pregnancy test is negative. Lila is pre-
ter, respond to the critical thinking questions that scribed the emergency contraceptive Plan B.
follow.
Critical Thinking Questions
Lila, a 19-year-old college student, comes to the clinic for
renewal of her prescription for OC pills. She finished her last 1. Lila asks you, the nurse, if it is too late to prevent preg-
pack of pills (Ortho-Novum) 10 days ago. She has been nancy. How would you respond to her question?
unable to get to the clinic to have her prescription renewed
before today. She remembers having unprotected intercourse 2. How does Plan B work to prevent pregnancy? What is
2 days ago, and now she is concerned that she will become another emergency contraceptive option that Lila
pregnant. Lila asks the nurse, “How can you help me?” could use?
A complete history and physical examination finds 3. What instructions would you give Lila regarding preg-
Lila in very good health. Her vital signs are temperature, nancy and Plan B for emergency contraception?
36.7°C (98°F); pulse, 68 beats/min; respiratory rate,
18 breaths/min; and blood pressure, 118/71 mmHg. Her Answers to Critical Thinking Questions are available on the
faculty resources site. Please consult with your instructor.
Additional Case Study 1. Explain the relationship between antibiotics and OCs.
Gina Martin, age 22, has been taking combination OCs for 2. What advice would you give Gina with regard to con-
the past 2 years. Her healthcare provider orders antibiotics tinuing the OC?
for a recurrent throat infection. As she is leaving the clinic,
she asks you, the nurse, if she should temporarily discon- Answers to Additional Case Study questions are available on
tinue her OC. the faculty resources site. Please consult with your instructor.
Chapter 70 Drugs for Modifying Conception 1305
Chapter Review 3. “Seasonique is taken for 2 months then off for
1 month using regular oral contraceptives.”
1. Estradiol–norethindrone (Ortho-Novum) is pre-
scribed for each of the following patients. Which 4. “Seasonique is taken for 84 days followed by
patients would the nurse consider at highest risk for 7 days of a lower dose that comes with the pack.”
an adverse response to this therapy? (Select all that
apply.) 4. The nurse is teaching the patient who has received a
prescription for mifepristone (Mifeprex) and misopro-
1. A 38-year-old with a body mass index classified as stol to terminate a pregnancy. When should the
overweight patient be instructed to take the misoprostol?
2. A 16-year-old athlete with asthma 1. Take it after taking one additional dose of
mifepristone (Mifeprex).
3. A 22-year-old who smokes two packs of cigarettes
per day 2. Take it 1 week after taking the mifepristone
(Mifeprex).
4. An 18-year-old with a history of chronic clinical
depression 3. Take it 24 to 48 hours after taking mifepristone.
4. Take it only if she is still bleeding in 3 days.
5. A 42-year-old who has delivered four healthy
children 5. The nurse is providing health education about contra-
ceptive methods to a group of young adults. Which of
2. The patient who is taking estradiol and drospirenone the following statements is correct about the use of
(Yasmin) informs the nurse that she forgot to take her spermicides?
pills for the past 2 days. Which response by the nurse
would be best when addressing this concern? 1. They are extremely effective in preventing pregnancy.
2. They have relatively low levels of effectiveness
1. “Take two pills today and tomorrow then resume
your normal dosage.” when used alone.
3. They are the main causes of HIV and pelvic
2. “Take one pill now and resume your normal
dosage time tomorrow.” inflammatory disease.
4. They can prevent ectopic pregnancy.
3. “Skip another day and then resume the normal
medication schedule.” 6. Rank the following contraceptive methods in order of
effectiveness from most to least effective:
4. “Stop taking the pills and have a pregnancy test
performed as soon as possible.” 1. Depo-Provera
2. Spermicides
3. The patient is interested in taking levonorgestrel– 3. Calendar rhythm
estradiol (Seasonique) and asks how to take it. Which 4. Oral contraceptives
would be the correct response provided by the nurse? 5. Transdermal (Ortho-Evra)
1. “Seasonique is taken one pill per day for 3 weeks, See Answers to Chapter Review in Appendix A.
then 1 week of ‘dummy pills’ with inert
ingredients.”
2. “Seasonique is taken year-round without a break
and without a period.”
References mortality in the United States, 2006–2010. Obstetrics &
Gynecology, 125(1), 5–12. doi:10.1097/
Abma, J. C., & Martinez, G. M. (2017). Sexual activity and AOG.0000000000000564
contraceptive use among teenagers in the United Curtis, K. M., Jatlaoui, T. C., Tepper, N. K., Zapata, L. B.,
States, 2011–2015. National Health Statistics Reports, Horton, L. G., Jamieson, J. D., & Whiteman, M. K.
no. 104. Hyattsville, MD: National Center for Health (2016). U.S. selected practice recommendations for
Statistics. contraceptive use, 2016. Morbidity and Mortality Weekly
Report Recommendations and Reports, 65(4), 1–66.
Branum, A. M., & Jones, J. (2015). Trends in long-acting doi:10.15585/mmwr.rr6504a1
reversible contraception use among U.S. women aged
15–44. NCHS Data Brief, 188, 1–8.
Creanga, A. A., Berg, C. J., Syverson, C., Seed, K., Bruce, F.
C., & Callaghan, W. M. (2015). Pregnancy-related
1306 Unit 10 Pharmacology of the Endocrine System Yeh, S., Kim, S., Ho, A., Schoenberger, S., Bakri, S., Ehlers,
J., & Thorne, J. (2015). Therapies for macular edema
Daniels, K., Daugherty, J., Jones, J., & Mosher, W. (2015). associated with central retinal vein occlusion: A report
Current contraceptive use and variation by selected by the American Academy of Ophthalmology.
characteristics among women aged 15–44: United States, Ophthalmology, 122, 769–778. doi:10.1016/j.ophtha.
2011–2013. Retrieved from https://www.cdc.gov/ 2014.10.013
nchs/data/nhsr/nhsr086.pdf
Simmons, K. B., & Edelman, A. B. (2016). Hormonal
contraception and obesity. Fertility and Sterility, 106,
1282–1288. doi:10.1016/j.fertnstert.2016.07.1094
Selected Bibliography Salcedo, J., Rodriguez, M. I., Curtis, K. M., & Kapp, N.
(2013). When can a woman resume or initiate
Centers for Disease Control and Prevention. (2017). contraception after taking emergency contraceptive
Pregnancy mortality surveillance system. Retrieved from pills? A systematic review. Contraception, 87, 602–604.
https://www.cdc.gov/reproductivehealth/ doi:10.1016/j.contraception.2012.08.013
maternalinfanthealth/pmss.html
Seidman, D., Hemmerling, A., & Smith-McCune, K.
Evans, G., & Sutton, E. L. (2015). Oral contraception. (2016). Emerging technologies to prevent pregnancy
Medical Clinics of North America, 99, 479–503. and sexually transmitted infections in women. Seminars
doi:10.1016/j.mcna.2015.01.004 in Reproductive Medicine, 34(3), 159–167. doi:10.1055/
s-0036-1571436
Finer, L. B., & Zolna, M. R. (2016). Declines in unintended
pregnancy in the United States, 2008–2011. New England Shoupe, D. (2016). LARC methods: Entering a new age of
Journal of Medicine, 374, 843–852. doi:10.1056/ contraception and reproductive health. Contraception
NEJMsa1506575 and Reproductive Medicine, 1, 4. doi:10.1186/s40834-
016-0011-8
Fok, W. K., & Blumenthal, P. D. (2016). Update on
emergency contraception. Current Opinion in Obstetrics Sobel, L., Salganicoff, A., & Rosensweig, C. (2017). The
and Gynecology, 28, 522–529. doi:10.1097/GCO. future of contraceptive coverage. Retrieved from http://
0000000000000320 kff.org/womens-health-policy/issue-brief/the-future-
of-contraceptive-coverage
Guttmacher Institute. (2017). American teens’ sexual and
reproductive health. Retrieved from https://www.
guttmacher.org/fact-sheet/american-teens-sexual-
and-reproductive-health
Pocius, K. D., & Dutton, C. R. (2015). Update on hormonal
contraception and obesity. Current Obstetrics and
Gynecology Reports, 4, 61–68. doi:10.1007/s13669-
014-0104-9
“What’s wrong with me? Dana
excites me so much, but when we
get into bed I just can’t please
her sexually.”
Patient “Mike Mayhew”
Chapter 71
Drugs for Disorders and Conditions
of the Male Reproductive System
Chapter Outline Learning Outcomes
cc Regulation of Male Reproductive Function After reading this chapter, the student should be able to:
cc Pharmacotherapy with Androgens
1. Explain the physiologic effects of androgens.
PROTOTYPE Testosterone, p. 1311
cc Anabolic Steroids 2. Describe the roles of the hypothalamus, pituitary,
cc Etiology of Male Sexual Dysfunction and testes in regulating male reproductive function.
cc Pharmacotherapy of Male Infertility
cc Pharmacotherapy of Erectile Dysfunction 3. Explain the role of androgens in the treatment of male
hypogonadism, delayed puberty, and breast cancer.
PROTOTYPE Sildenafil (Viagra), p. 1317
cc Pathophysiology of Benign Prostatic Hyperplasia 4. Describe the potential consequences associated with
cc Pharmacotherapy of Benign Prostatic Hyperplasia the use of anabolic steroids to enhance athletic
performance.
Alpha1-Adrenergic Antagonists
5-Alpha Reductase Inhibitors 5. Identify the types and causes of male sexual
PROTOTYPE Finasteride (Proscar), p. 1322 dysfunction disorders.
6. Explain the role of drugs in the management of male
infertility.
7. Describe the etiology, pathogenesis, and
pharmacotherapy of erectile dysfunction.
8. Describe the pathogenesis and pharmacotherapy of
benign prostatic hyperplasia.
9. Compare and contrast the nonpharmacologic and
pharmacologic management of disorders and
conditions of the male reproductive system.
10. For each of the classes shown in the chapter outline,
identify the prototype and representative drugs and
explain the mechanism(s) of drug action, primary
indications, contraindications, significant drug
interactions, pregnancy category, and important
adverse effects.
11. Apply the nursing process to the care of patients
receiving pharmacotherapy for disorders and
conditions of the male reproductive system.
1307
1308 Unit 10 Pharmacology of the Endocrine System
Key Terms
anabolic effects, 1313 corpora cavernosa, 1316 libido, 1309
anabolic steroids, 1313 erectile dysfunction (ED), 1316 oligospermia, 1315
androgens, 1308 hypogonadism, 1309 virilization, 1308
azoospermia, 1315 impotence, 1316
benign prostatic hyperplasia interstitial endocrine (Leydig)
(BPH), 1319 cells, 1308
As in women, reproductive function in men is regulated by growth, which contributes to the differences in muscle
a small number of hormones from the hypothalamus, pitu- strength and body composition between men and women.
itary, and gonads. Because hormonal secretion in men is Testosterone promotes the synthesis of erythropoietin,
relatively constant throughout the adult lifespan, the phar- resulting in an increased production of red blood cells
macologic treatment of reproductive disorders in men is (RBCs) and accounting for the higher hemoglobin and
less complex and more limited than in women. This chap- hematocrit levels found in males.
ter examines the drugs used to treat the disorders and con-
ditions of the male reproductive system. Androgen secretion is regulated by the same pituitary
hormones that control reproductive function in women.
Regulation of Male Reproductive Although the name follicle-stimulating hormone (FSH)
Function applies to its target in the female ovary, this same hormone
influences testosterone secretion in men. Luteinizing
71.1 Male reproductive function is controlled hormone (LH), more accurately called interstitial cell–
through the secretion of androgens. stimulating hormone (ICSH) in the male reproductive sys-
tem, regulates the production of testosterone by the interstitial
Male reproduction function is controlled by androgens, endocrine cells of the testes. Unlike the 28-day cyclic secretion
which are hormones secreted by interstitial endocrine of estrogen and progesterone in women, testosterone secre-
(Leydig) cells in the testes. Testosterone, the primary andro- tion is relatively constant in adult men. Beginning in puberty,
gen, is responsible for maturation of the male reproductive testosterone production increases rapidly and continues to
system and the secondary sex characteristics of men. Other maintain a high level of production until later adulthood,
important androgens include androstenedione and dehydro- after which it slowly declines. Normal plasma concentrations
epiandrosterone (DHEA). Androgens are sometimes referred of testosterone are 250 to 1000 mg/dL. If the level of testoster-
to as anabolic steroids. one in the blood rises above normal, negative feedback to the
pituitary shuts off the secretion of LH and FSH. The relation-
Androgens are responsible for the development of the ship among the hypothalamus, pituitary, and the male repro-
male urogenital system in the fetus. After birth the interstitial ductive hormones is illustrated in Figure 71.1.
endocrine cells are quiet until activated by the gonadotropins,
which are hormones secreted by the pituitary gland. The Precursor molecules of testosterone, androstenedione
resulting increased production of testosterone by the testes and DHEA, are secreted in small amounts by the adrenal
begins the cascade of changes that accompany the onset of glands. Their production in the adrenal gland is controlled
puberty in the male adolescent. The increased testosterone lev- by the secretion of adrenocorticotropic hormone (ACTH).
els are responsible for the process of virilization, or the devel- These weaker androgens are converted to testosterone once
opment of the male sexual characteristics. During the next they reach peripheral tissues. Adrenal androgens have a
several years, the testes, scrotum, and penis enlarge until they role in the growth of pubic hair and are thought to influence
reach adult proportions. Pubic and axillary hair grows and the skeletal growth spurt in adolescents. In adult men, the
other body hair becomes more adult-like in nature. The pro- adrenal androgens have minimal effects due to the compar-
duction of sperm that are capable of fertilizing an ovum begins atively larger amount of testosterone secreted by the testes.
in the seminiferous tubules of the testes. The cartilage of the
larynx grows, causing the deeper toned male voice. Sebaceous Pharmacotherapy with Androgens
gland activity is stimulated, resulting in an increase in the level
of acne. The final change is the growth of facial hair. 71.2 Androgens are used to treat hypogonadism
and delayed puberty in males, and breast cancer
Testosterone also has profound metabolic effects in in females.
nonreproductive tissues. Of particular importance is its
ability to build skeletal muscle mass and to stimulate bone Androgens are used to treat testosterone deficiency in
men, delayed puberty, oligospermia, hypogonadism,
Chapter 71 Drugs for Disorders and Conditions of the Male Reproductive System 1309
anemia, muscle-wasting disorders, and certain cancers.
)P4* *[RQVJCNCOWU These hormones are listed in Table 71.1.
Lack of sufficient testosterone secretion by the testes
can result in male hypogonadism. Hypogonadism may be
1 congenital or acquired later in life. When the condition is
caused by a testicular disorder, it is called primary hypogo-
2KVWKVCT[ nadism. Examples of disease states that may cause primary
testicular failure include mumps, testicular trauma or
2 inflammation, and certain autoimmune disorders.
1 A deficiency in FSH and LH secretion by the pituitary
will result in a lack of stimulus to the testes to produce
androgens. Lack of FSH and LH secretion may have a num-
ber of causes, including Cushing’s syndrome, thyroid dis-
orders, estrogen-secreting tumors, and therapy with
0GICVKXG .* (5* gonadotropin-releasing hormone (GnRH) agonists such as
HGGFDCEM leuprolide (Lupron). Hypogonadism that is caused by
1 1 defects in the pituitary or hypothalamus is known as sec-
ondary hypogonadism.
Insufficient testosterone secretion may delay the onset
of puberty. If total lack of testosterone secretion occurs,
puberty will not occur. In adult men, symptoms of hypogo-
nadism include diminished secondary sex characteristics
2 such as sparse axillary, facial, and pubic hair; increased sub-
cutaneous fat; reduced muscle mass; and smaller testes. The
lack of testosterone can lead to erectile dysfunction (ED);
low sperm counts (oligospermia); a decrease in the amount
r +PETGCUGF VGUVQUVGTQPG UGETGVKQP of ejaculate; and decreased libido, or a lack of interest in
r 5VKOWNCVKQP QH URGTOCVQIGPGUKU sexual intercourse. Nonspecific complaints may include
behavioral and mood changes such as irritability, fatigue,
depression, and a general loss of motivation.
Figure 71.1 Hormonal control of the male reproductive hormones. Hypogonadism is confirmed by obtaining serum tes-
tosterone levels. Assessment of LH and FSH levels, as well
Table 71.1 Selected Androgens and Anabolic Steroids
Drug Route and Adult Dose Adverse Effects
(Maximum Dose Where Indicated)
Acne, gynecomastia, hirsutism and male sex
fluoxymesterone PO: 5–20 mg/day characteristics (in women), sodium and water
retention, emotional lability, amenorrhea,
methyltestosterone (Android, Methitest, Testred) PO: 10–50 mg/day decreased libido, hypercholesterolemia
Buccal: 5–25 mg/day
Anaphylaxis, testicular atrophy, and
nandrolone IM: 50–200 mg/wk oligospermia at high doses; priapism, peliosis
hepatis, benign intracranial hypertension
oxandrolone (Oxandrin) PO: 2.5–20 mg/day divided bid–qid for 2–4 wk (HTN), thromboembolism
oxymetholone (Anadrol-50) PO: 1–5 mg/kg/day
testosterone (buccal patch: Striant) Buccal: 30 mg q12h
(transdermal patch: Androderm)
(topical gels: AndroGel, Fortesta, Testim, Vogelxo) Transdermal: Apply one to two 2.5-mg patches daily
(implantable pellets: Testopel) (max: 5 mg/day)
(nasal spray: Natesto)
Gel: Apply 5–50 g daily, depending on product
Pellets: 150–450 mg every 6 months
(each pellet is 75 mg)
Nasal spray: 1 spray in each nostril tid
testosterone cypionate (Depo-Testosterone) IM: 50–400 mg q2–4wk
testosterone enanthate (Delatestryl) IM: 50–400 mg q2–4wk
testosterone undecanoate (Aveed) IM: 750 mg initially, followed by the same dose
at 4 wk and q10wk thereafter
Note: Italics indicate common adverse effects. Underline indicates serious adverse effects.
1310 Unit 10 Pharmacology of the Endocrine System
as prolactin, estradiol, and thyroid hormone levels, may be Testosterone formulations: Testosterone is available in
useful in determining causation. Low serum levels of tes- a wide variety of formulations. All are equally effective
tosterone concurrent with normal or elevated levels of FSH and the choice is based on healthcare provider experience,
and LH suggest that the testes are unresponsive to hor- ease of use, and the personal preference of the patient.
monal activation; thus the patient has primary hypogonad- Common to all dosage forms is the need for regular fol-
ism. If testosterone, FSH, and LH levels are all low, this low-up healthcare visits to ensure that the serum testoster-
would indicate secondary hypogonadism. one level is maintained within the designated range.
Pharmacotherapy of hypogonadism includes replace- Intramuscular (IM) testosterone: Testosterone cypionate
ment therapy with testosterone or other androgens. For (Depo-Testosterone), testosterone undecanoate (Aveed),
boys experiencing delayed puberty, puberty is generally and testosterone enanthate (Delatestryl) are IM forms of
induced when the boy reaches 15 to 17 years of age using a testosterone. These drugs are slowly absorbed, metabo-
long-acting testosterone preparation. A 6-month period of lized to free testosterone, and result in blood levels that
androgen therapy is given, followed by 6 months without will vary widely after administration. This variation in
the drug. If further therapy is needed, then testosterone serum levels may cause patients to experience fluctua-
cypionate (Depo-Testosterone) may be administered every tions in their libido and energy and experience mood
2 to 4 weeks. Therapy may be continued for up to 4 years. swings. Patients tend to report soreness at the site of injec-
Once appropriate physiologic hormonal levels have been tion. IM injections are given deep in the gluteal muscle
attained, the normal progression of pubertal changes typi- every 2 to 4 weeks.
cally occurs.
Implantable testosterone pellets: Testopel is a long-
In the adult patient a variety of testosterone replace- acting form of testosterone that is implanted subcutane-
ment preparations are available. The patient should experi- ously, usually on the anterior abdominal wall. One to six
ence improved libido, increased amount of ejaculate, and pellets are implanted depending on the dose required.
correction of ED within days or weeks of initiating therapy. Testosterone levels are obtained regularly during ther-
Male sex characteristics become better defined, depression apy and the number of pellets adjusted accordingly. To
resolves, and muscle strength rapidly improves. Therapy induce puberty, low doses are usually used for 4 to
with androgens is targeted to return serum testosterone to 6 months. For adult replacement therapy higher doses
normal physiologic levels. Above-normal levels serve no are administered, with the effectiveness of the pellets
therapeutic purpose and increase the risk of adverse effects. lasting 3 to 4 months.
Nonreproductive uses: Because androgens have wide- Transdermal testosterone patch: The Androderm patch is
spread physiologic effects, they have been used to treat applied to the upper arm, thigh, back, or abdomen,
certain nonreproductive disorders. Testosterone promotes rotating application sites. The patch is not to be applied
the synthesis of erythropoietin, which is essential for RBC to the scrotum or to damaged skin. A rash at the site of
production, and the drug may be used to correct anemia the application tends to be the only adverse effect noted.
unresponsive to other treatments. These indications The patches are applied in the evening and changed
include aplastic anemia and anemias associated with daily. Because the used patches contain some testoster-
chronic kidney disease and chemotherapy. Taking advan- one, they should be disposed of safely, away from
tage of the anabolic effects of testosterone on bone and children and pets.
skeletal muscle, the drug is sometimes given to debilitated
patients who have muscle-wasting disease, such as that Transdermal testosterone gel: AndroGel, Fortesta, Testim,
seen in patients with acquired immunodeficiency syn- and Vogelxo are testosterone gels that are indicated for the
drome (AIDS). treatment of hypogonadism. The drug is applied once daily
in the morning to clean and dry skin of the upper arms,
High doses of androgens are occasionally used for the shoulders, or abdomen (not the genitals). Showering or
palliative management of certain types of breast cancer in swimming should be avoided for several hours after appli-
combination with other antineoplastics. The high doses cation to avoid washing off the drug. The alcohol-based
required for breast cancer treatment will cause virilization gels dry quickly: The testosterone is absorbed in the skin in
in women. Androgen therapy is contraindicated in males about 30 minutes and released slowly to the blood. Many
with breast cancer because it promotes the growth of the patients prefer the gels because they cause less local irrita-
cancer. Similarly, because the growth of most prostate carci- tion, do not fall off like the patches, and deliver a more con-
nomas is testosterone dependent, androgens should not be sistent level of testosterone. A disadvantage is that the gel
prescribed for older men unless the possibility of prostate can be transferred to another individual by skin-to-skin
cancer has been ruled out. Patients with prostate carcinoma contact, causing virilization of female contacts and poten-
are sometimes given a GnRH agonist such as leuprolide tial fetal harm. Testosterone levels should be measured
(Lupron) to reduce circulating testosterone levels.
Chapter 71 Drugs for Disorders and Conditions of the Male Reproductive System 1311
after a few weeks of therapy and at regular intervals Pharmacokinetics: Buccal, transdermal, IM,
thereafter to ensure that physiologic levels have been Route(s) implantable pellets
achieved.
Absorption Cypionate and enanthate are
Approved in 2014 by the U.S. Food and Drug Admin- slowly absorbed from IM sites
istration (FDA), Natesto delivers testosterone gel via intra- Distribution
nasal spray. Absorption is rapid across the nasal mucosa, 98% bound to sex hormone–
but the drug needs to be applied three times daily. The Primary metabolism binding globulin; unknown if
most common side effects are nasal related and include Primary excretion secreted in breast milk
nasopharyngitis, rhinorrhea, and epistaxis. Onset of action
Hepatic
Testosterone buccal tablets: Striant is a form of testoster- Duration of action
one that produces a continuous supply of testosterone in 90% renal, 6% feces
the blood. Patients are instructed to place a tablet in the
gum area just above the incisor, holding it in place for Steady-state levels are reached
30 seconds. Usual doses are one tablet every 12 hours, in 3–4 weeks
alternating sides of the cheek. Patients may eat, drink, and
chew gum with the buccal tablet in place. This route exhib- 2–4 weeks cypionate and enan-
its only minor adverse effects such as local irritation to the thate; half-life: 10–100 min
area, bad taste, and altered taste perceptions.
Adverse Effects: Androgens may cause either
PROTOTYPE DRUG Testosterone decreased or increased libido. Salt and water are often
retained, causing edema, and a diuretic may be indicated.
Classification Therapeutic: Male sex hormone Liver damage and hepatic cancer are potentially seri-
Pharmacologic: Androgen, anabolic ous adverse effects and are of special concern when high
doses are taken for prolonged periods. Acne and skin
steroid, antineoplastic irritation are common during therapy. High doses may
suppress spermatogenesis, reduce ejaculatory volume,
Therapeutic Effects and Uses: The primary thera- and cause oligospermia. Black Box Warning: Virilization
peutic use of testosterone is to treat delayed puberty and in children and women may occur following secondary
hypogonadism in boys by promoting virilization, includ- exposure. Children and women should avoid touching
ing maturation of the sexual organs, growth of facial hair, the application sites in men using testosterone gel. Signs
and a deepening of the voice. In adult men testosterone of virilization in women include suppression of ovula-
administration will increase libido and restore mascu- tion, lactation, or menstruation; hoarseness or deepening
line characteristics that may be deficient. Testosterone is of their voice, which is often irreversible; hirsutism; oily
approved to treat ED when the cause is associated with skin; clitoral enlargement; regression of breasts; and male-
low androgen levels. The drug is also approved for the pattern baldness.
palliative treatment of inoperable breast cancer in women.
Off-label indications for testosterone include treatment Contraindications/Precautions: Testosterone is
of postpubertal cryptorchidism, microphallus, anemia contraindicated in men with known or suspected breast or
in patients with chronic kidney disease (CKD), female- prostatic carcinomas because it can promote the growth of
to-male gender change, and AIDS-associated wasting these tumors. It is contraindicated in women who are or
syndrome. may become pregnant (category X). The drug may worsen
prostatic hyperplasia. Testosterone should be used with
Testosterone base is administered by the IM route, caution in patients with CKD or hepatic impairment. Cau-
although other salts are available for the transdermal, tion must be used if testosterone is administered to patients
implantable pellets, and buccal routes. Testosterone was with diabetes mellitus, history of myocardial infarction
classified as a Schedule III controlled substance in 1991 (MI), coronary artery disease (CAD), benign prostatic
because it was being widely abused by weight lifters and hyperplasia (BPH), and acute intermittent porphyria and
other athletes. in geriatric patients. Monitoring of serum cholesterol and
serum electrolytes, as well as liver function tests, is needed
Mechanism of Action: Testosterone binds to specific throughout therapy because testosterone may increase
receptors located in the cell cytoplasm. The hormone- these values.
receptor complex then migrates to the nucleus where it
acts on the deoxyribonucleic acid (DNA) to promote the Drug Interactions: Testosterone may potentiate the
synthesis of specific messenger ribonucleic acid (mRNA) effects of oral (PO) anticoagulants and increase the risk
molecules. These form templates for the production of spe- of severe bleeding. Concurrent use of testosterone with
cific proteins that mediate testosterone effects. corticosteroids may cause additive edema, which can be
a serious concern for those with heart failure. Hepatotoxic
1312 Unit 10 Pharmacology of the Endocrine System
drugs should be avoided because their use with testoster- women. This drug has the same adverse effects, contrain-
one can cause additive liver damage. The 5-alpha reduc- dications, and actions as those of testosterone. Like other
tase drugs (finasteride) used to treat prostatic hyperplasia androgens, hepatitis and hepatic neoplasms may occur
are antiandrogenic and their use with testosterone will with long-term use. Fluoxymesterone should be used with
inhibit the therapeutic effects of both drugs. Herbal/Food: caution in patients with preexisting cardiac or CKD
Insulin requirements may decrease, and the risk of hepa- because the edema caused by the drug can worsen these
totoxicity may increase when used with echinacea. Evalu- disorders. Older men have an increased risk for prostate
ation of calcium levels is necessary because hypercalcemia cancer when taking androgens.
may result.
Methyltestosterone (Android, Methitest, Testred): Methyl-
Pregnancy: Category X. testosterone is available as PO tablets, capsules, or buccal
tablets. It is indicated for male hypogonadism, delayed
Treatment of Overdose: There is no specific treat- male puberty, and inoperable breast cancer in women.
ment for overdose. This drug has the same adverse effects, contraindications,
and actions as those of testosterone. Caution must be used
Nursing Responsibilities: Key nursing implica- during long-term use because of the potential for hepato-
tions for patients receiving testosterone are included in the toxicity and for the development of prostate cancer in
Nursing Practice Application for Patients Receiving Phar- older men.
macotherapy with Androgens.
Oxandrolone (Oxandrin): Originally approved in 1964,
Drugs Similar to Testosterone oxandrolone is an anabolic steroid with actions and
adverse effects that are the same as testosterone. It is
Other androgens include fluoxymesterone, methyltestos- approved to promote weight gain in patients who are
terone, and oxandrolone. All are pregnancy category X. severely ill, to decrease bone pain that accompanies osteo-
porosis, and to offset protein catabolism associated with
Fluoxymesterone: Approved in 1983, fluoxymesterone is prolonged administration of corticosteroids.
a PO androgen that is indicated for male hypogonadism
and the palliative therapy of inoperable breast cancer in
CONNECTIONS: NURSING PRACTICE APPLICATION
Patients Receiving Pharmacotherapy with Androgens
Assessment
Baseline assessment prior to administration:
• Obtain a complete health history including cardiovascular, peripheral vascular, thyroid, hepatic, or kidney disease; diabetes; prostatic hyperplasia; or
breast cancer.
• Obtain a drug history including allergies, current prescription and OTC drugs, herbal preparations, alcohol use, and smoking. Be alert to possible drug
interactions.
• Evaluate appropriate laboratory findings (e.g., complete blood count [CBC], electrolytes, glucose, lipid levels).
• Obtain baseline height, weight, and vital signs.
• Assess the patient’s ability to receive and understand instructions. Include family and caregivers as needed.
Assessment throughout administration:
• Assess for desired therapeutic effects (e.g., hormone levels normalize, normal signs of masculinization are present).
• Continue periodic monitoring of CBC, electrolytes, glucose, lipid levels, hepatic and kidney function laboratory values.
• Monitor vital signs, height, and weight at each healthcare visit.
• Assess for adverse effects: nausea, vomiting, headache, weight gain, fluid retention, edema, increased blood pressure (BP), changes in mood, irritabil-
ity, or agitation. Immediately report tachycardia, palpitations, HTN, especially associated with angina or dyspnea, or abdominal pain, especially right
upper quadrant and associated with yellowed skin or sclera, darkened urine, or clay-colored stools.
Implementation
Interventions and (Rationales) Patient-Centered Care
Ensuring therapeutic effects: • Teach the patient the appropriate administration techniques.
• Monitor appropriate medication administration for optimal results.
(Appropriate administration, especially of gels or transdermal forms, will
optimize drug absorption and therapeutic effects.)
Minimizing adverse effects: • Teach the patient to monitor BP on a weekly basis. Report any BP over
• Monitor BP at each clinical visit. Check weight and for the presence of 140/90 mmHg, or as directed, to the healthcare provider. Report any
weight gain of 1 kg (2 lb) in 24 h or 2 kg (5 lb) in 1 wk to the healthcare
edema. (Androgens cause sodium and water retention with resulting provider. Report any peripheral edema. Ensure proper functioning of
increases in weight, BP, and possible edema. Immediately report any any equipment used at home.
BP over 140/90 mmHg, peripheral edema, or weight gain.)
Chapter 71 Drugs for Disorders and Conditions of the Male Reproductive System 1313
CONNECTIONS: NURSING PRACTICE APPLICATION (continued)
Implementation
Interventions and (Rationales) Patient-Centered Care
• Continue to monitor electrolytes, lipid levels, and hepatic function • Instruct the patient to return periodically for laboratory tests.
laboratory values periodically. (Androgens may cause increases in cho- • Teach the patient to immediately report any symptoms of abdominal or
lesterol and calcium levels. Hepatotoxicity and hepatic neoplasms are
rare but potential adverse effects. Lifespan: Age-related physiologic right upper quadrant discomfort or pain, yellowing of the skin or sclera,
differences may place the older adult at greater risk for hepatotoxicity.) fatigue, anorexia, darkened urine, clay-colored stools, weakness,
lethargy, nausea, or vomiting.
• Monitor blood glucose levels in patients with diabetes more frequently. • Teach men with diabetes to monitor capillary blood sugar more
Report consistent elevations to the healthcare provider. (Androgens may frequently while on the drug and to report consistent elevations to the
affect carbohydrate metabolism, leading to increased glucose levels.) healthcare provider.
• Monitor height and growth in children and adolescents. (Androgen • Teach the patient, family, or caregiver to measure height once per
administration may result in premature closure of epiphyseal bone end- month or as directed. Return for clinical assessments as needed,
ings and loss of normal growth patterns.) approximately every 6 months, to monitor bone growth.
• Monitor drug use in adolescent patients. (Abuse of androgens and • Teach the adolescent patient, family, or caregiver to maintain daily
anabolic steroids may occur, along with resulting adverse effects.) dosing as instructed and not to increase the dosage unless instructed
to do so by the healthcare provider. The drug should never be shared
with others.
Patient understanding of drug therapy: • The patient, family, or caregiver should be able to state the reason for
• Use opportunities during administration of medications and during the drug, appropriate dose and scheduling, what adverse effects to
observe for, and when to report them.
assessments to discuss the rationale for drug therapy, desired thera-
peutic outcomes, commonly observed adverse effects, parameters
for when to call the healthcare provider, and any necessary monitoring
or precautions. (Using time during nursing care helps to optimize and
reinforce key teaching areas.)
Patient self-administration of drug therapy: • Teach the patient to take the drug following appropriate guidelines:
• When administering the medication, instruct the patient or caregiver in • Oral drugs should be taken at the same time each day to help with
remembering the dose.
proper self-administration of the drug, e.g., consistently at the same • Transdermal patches (e.g., Testoderm, Androderm) should be
time each day to help with remembering to take the dose, followed by applied to the upper arm, thigh, back, or abdomen. Change the
teach-back. (Utilizing time during nurse administration of these drugs patch and rotate sites daily, and report any skin irritation. Discard
helps to reinforce teaching.) used patches safely in the trash. Do not apply the patch to the
scrotal area or on broken or irritated skin.
• Buccal tablets (e.g., Striant) should be placed between the cheek
and upper gum near the incisor and held in place for 30 seconds.
Eating, drinking, and chewing gum may continue while the tablet is
in place. Rotate from side to side, avoiding areas of irritation.
• Gels and creams (e.g., AndroGel and Testim) should be applied to
the upper arms, shoulders, or abdomen. Do not apply to the scrotal
area or to broken or irritated skin. Swimming and showering should
be avoided for several hours following administration. Do not allow
women or children to come in contact with the drug or application
sites, because the drug may rub off and cause adverse effects.
• Transdermal pellets (e.g., Testopel) are implanted in the abdominal
wall every 3–6 months.
• Injections should be given into deep gluteal muscle. If the patient is
to administer his own injections, teach the appropriate technique,
followed by teach-back until the patient is comfortable and demon-
strates proper technique.
Anabolic Steroids effects. They are often taken inappropriately by athletes
who hope to build muscle mass and strength, thereby
71.3 Often abused by athletes, anabolic steroids obtaining a competitive edge. The use of anabolic steroids
can cause serious adverse effects. to improve athletic performance is illegal and all major ath-
letic organizations prohibit the use of anabolic steroids by
Testosterone has both androgenic and anabolic effects. Its their participants. Many adolescents take these drugs to
androgenic effects are responsible for creating and main- enhance their appearance, rather than to compete in
taining the male sexual characteristics. The hormone’s athletics.
anabolic effects relate to its ability to accelerate the growth
of RBCs, muscle, bone, and neural tissues. Interestingly, despite their regulation, some formula-
tions of anabolic steroids can be purchased over the coun-
Anabolic steroids also include testosterone-like sub- ter (OTC) or online. They are promoted as natural steroid
stances that were originally developed to produce the ana- alternatives for building muscle mass. FDA-approved
bolic effects of androgens while minimizing the androgenic
1314 Unit 10 Pharmacology of the Endocrine System
anabolic steroids, including all testosterone products, Etiology of Male Sexual
oxandrolone, oxymetholone, and nandrolone, are classified Dysfunction
as Schedule III drugs under the Anabolic Steroid Control
Acts of 1990 and 2004 because of their abuse potential. The 71.4 Male sexual dysfunction may have both
anabolic steroids are listed in Table 71.1 medical and psychologic etiologies.
PharmFACT Approximately 50% of men will experience some form of
sexual dysfunction during their adult life. The primary
In 2013, approximately 3% of 12th-grade boys and about 1% types of male dysfunction disorders may be classified as
of 12th-grade girls reported having taken anabolic steroids at follows:
some time in their life. This is about 50% fewer than reported
in 2002 (LaBotz & Griesemer, 2016). • Diminished libido: lack of interest in sexual activity
• Erectile dysfunction (ED): inability to obtain or main-
When taken in large doses for prolonged periods, ana-
bolic steroids can produce significant adverse effects, some tain an erection
of which may persist for months after discontinuation of • Ejaculation disorder: premature, delayed, or retro-
the drugs. When given in higher doses, androgen sup-
presses the release of LH and FSH, resulting in oligosper- grade ejaculation
mia, testicular atrophy, and impotence in men. In female • Infertility: inability to conceive a child.
athletes menstrual irregularities are likely with an obvious
increase in masculine appearance, such as hair growth and Certain causes of male sexual dysfunction are treat-
reduction in breast size. When administered to children able, either medically or surgically, or can be improved to
and teens, androgens can promote premature epiphyseal the degree that a couple can achieve successful conception
plate closure, thereby reducing adult height. Anabolic ste- or maintain a satisfactory sexual lifestyle. For example,
roids are hepatotoxic, and permanent liver damage or therapy with testosterone can rapidly increase libido in
hepatic carcinoma may result with prolonged use. Accom- patients who have insufficient serum testosterone levels or
panying salt and water retention can result in hypertension hypogonadism. Many men with ED can now be success-
(HTN). These drugs tend to raise low-density lipoprotein fully treated with medications.
(LDL) and lower high-density lipoprotein (HDL) choles-
terol levels, possibly accelerating atherosclerosis. Acne is A large number of drugs can cause or worsen male sex-
common. Behavioral changes include an increase in aggres- ual dysfunction, as listed in Table 71.2. In most cases, the
sive behavior and psychologic dependence. Another dysfunction is dose related and is much less evident when a
unusual adverse effect is peliosis hepatis, which is a condi- single drug is taken at low doses. However, taking multiple
tion in which liver, and sometimes splenic, tissue is replaced drugs that have the potential to cause sexual adverse effects
with blood-filled cysts. These cysts are sometimes asymp- may result in additive sexual dysfunction. The two most
tomatic and may not be recognized until life-threatening common drug classes that cause sexual dysfunction are
hepatic failure or intra-abdominal hemorrhage occurs. antihypertensives and antidepressants. Because sexual
Anabolic steroids are pregnancy category X medications adverse effects are a potential cause of nonadherence,
and their use is contraindicated during pregnancy. nurses should ask specific questions regarding changes in
sexual function when their patients are taking these drugs.
In 2016, the FDA added new warning labels to all tes-
tosterone products and other prescription anabolic ste- Many comorbid medical conditions are associated
roids. The new label is intended to alert prescribers to the with sexual dysfunction. Conditions that result in general
abuse and dependence potential of these products and to debility, such as pain, muscle weakness, shortness of
the serious adverse effects that can result from abuse. It breath, or stroke, may cause dysfunction. Diabetes and
also advises healthcare providers of the importance of mea- HTN are the two chronic medical conditions most fre-
suring serum testosterone when abuse is suspected. quently associated with male sexual dysfunction. Patients
who present with psychologic conditions such as anxiety
CONNECTION Checkpoint 71.1 and depression have a high incidence of sexual dysfunc-
tion. Other factors associated with ED include obesity and
Anabolic steroids are often taken illegally by “stacking” or “pyramid- cigarette smoking. Combining multiple risk factors, for
ing.” From what you learned in Chapter 27, define the use of these example, a man who has diabetes, is obese, takes antihy-
terms in the abuse of these drugs. Answers to Connection Check- pertensive drugs, and smokes, will result in a high risk for
point questions are available on the faculty resources site. Please consult sexual dysfunction.
with your instructor.
Nurses play a key role in treating male sexual dysfunc-
tion by obtaining a thorough medical history and by recog-
nizing factors that contribute to the disorder. Should
patients experience unacceptable sexual adverse effects
from their medications, alternative drugs can usually be
Chapter 71 Drugs for Disorders and Conditions of the Male Reproductive System 1315
Table 71.2 Selected Drugs That May Cause or Worsen cause is Klinefelter’s syndrome, which is the presence of an
extra X chromosome. Acquired infertility may result from
Male Sexual Dysfunction testicular trauma; pituitary or hypothalamus disorders;
and infections such as mumps, chronic tuberculosis, and
Drug/Drug Class Sexual Adverse Effect(s) sexually transmitted infections. Infertility may occur with
or without signs of hypogonadism. Rarely, life-threatening
Antihypertensives Retrograde ejaculation, priapism conditions such as testicular cancer and pituitary tumors
may be the cause. In addition, the lack of ability to conceive
alpha1-adrenergic antagonists ED may be caused by factors such as ED or ejaculation disor-
(e.g., alfuzosin, tamsulosin) ders. Identifying the etiology of infertility is important
Diminished libido, ED because not all causes can be successfully treated with
angiotensin-converting enzyme pharmacotherapy.
(ACE) inhibitors (e.g., lisinopril) Diminished libido, ED
Diminished libido, ED, gynecomastia The most obvious etiology of male infertility is lack of
beta-adrenergic antagonists ED sufficient sperm production. Oligospermia is the presence
(e.g., propranolol) of less than 20 million sperm per milliliter of ejaculate.
ED Azoospermia, which occurs in 15% of men with infertility,
methyldopa Inhibited ejaculation, priapism is the complete absence of sperm in ejaculate. Azoospermia
ED can be caused by severely reduced or absent sperm produc-
spironolactone Diminished libido, ED, inhibited tion, or it may indicate an obstruction of the vas deferens or
ejaculation, priapism ejaculatory duct that can be corrected surgically. Drug ther-
thiazide diuretics Anorgasmy, inhibited ejaculation, apy with calcium channel blockers, colchicine, spironolac-
Nervous System Drugs diminished libido tone, and cimetidine can lower sperm production.
Priapism
carbamazepine Diminished libido, ED, inhibited Depending on the cause of the condition, one goal of
ejaculation pharmacotherapy for male infertility may be to increase
haloperidol sperm production. If the cause of the infertility is decreased
ED testosterone secretion due to hypogonadism, administra-
lithium carbonate Infertility tion of this hormone can increase sperm production and
Infertility cure the condition.
phenothiazines
(e.g., chlorpromazine) Diminished libido, ED, gynecomastia Another method of increasing sperm production is to
ED stimulate the testes with pituitary hormones. Pharmaco-
selective serotonin reuptake Diminished libido, ED, gynecomastia therapy often begins with IM injections of human chorionic
inhibitors (e.g., fluoxetine) Infertility gonadotropin (HCG) 3 times per week over 1 year.
Although HCG is secreted by the placenta, its effects in
trazodone men are identical to those of LH: increased testosterone
secretion and spermatogenesis. Sperm counts are con-
tricyclic antidepressants ducted periodically to assess therapeutic progress. If HCG
(e.g., imipramine) is unsuccessful, therapy with menotropins (Menopur,
Other Drugs Repronex) or newer recombinant forms of FSH may be
attempted. Menotropins consists of a mixture of purified
alcohol FSH and LH, which increases testosterone and sperm
production.
anabolic steroids
Once testosterone levels rise, either through the
antineoplastics administration of testosterone or HCG, the natural feed-
(e.g., cyclophosphamide) back mechanism of the body will signal the pituitary to
shut down testosterone secretion in the testes. To boost tes-
cimetidine tosterone levels, antiestrogen drugs such as tamoxifen
(Nolvadex) and clomiphene (Clomid) have been used to
digoxin block the negative feedback of adrenal estrogen to the
pituitary and hypothalamus, thus increasing the levels of
finasteride FSH and LH. Unfortunately, these drugs produce only a
small increase in sperm count and can produce such
methotrexate adverse effects as gynecomastia, decreased libido, and
weight gain. Clomiphene is presented as a prototype drug
substituted. Encouraging patients to receive treatment for for female infertility in Chapter 69.
anxiety, depression, and other comorbid conditions some-
times helps improve the sexual dysfunction. All men at risk
for ED should be encouraged to maintain optimal weight,
stop smoking, and limit their alcohol use.
Pharmacotherapy of Male
Infertility
71.5 Male infertility is treated with endocrine
drugs that boost sperm production.
Infertility affects approximately 6.1 million people in the
United States, or roughly 10% of the reproductive age pop-
ulation. It is estimated that 30% to 40% of infertility among
couples is due to difficulties with the male reproductive
system.
Like female infertility, male infertility may have a
number of complex causes. The most common congenital
1316 Unit 10 Pharmacology of the Endocrine System
Other pharmacologic approaches to treating male Urinary bladder
infertility have been attempted. If retrograde ejaculation
has been identified as a probable cause, sympathomimetics Ureteral
may be used to convert to normal, antegrade ejaculation. opening
Various nutritional supplements, such as zinc to improve
sperm production, L-carnitine to improve sperm motility Prostate
and sperm count, and vitamins C and E as antioxidants to gland
reduce reactive intermediates, have been tested. Unfortu-
nately these and other therapies have not conclusively Urethra
been shown to have any positive effect on male infertility.
Openings of
Drug therapy of male infertility is not as successful as bulbourethral
pharmacotherapy in women because only about 5% of glands
infertile men have an endocrine etiology for their disorder.
Many years of therapy may be required. Because of the Corpus
expense of pharmacotherapy, the large number of injec- spongiosum
tions needed, and the relative lack of success, other means
of conception for the infertile man should be explored. A Corpus
wide range of assistive reproduction procedures, includ- cavernosum penis
ing in vitro fertilization or intrauterine insemination, may
be pursued.
CONNECTION Checkpoint 71.2
Clomiphene is used for both male and female infertility. From what
you learned in Chapter 69, how does this drug act to improve female
fertility? Answers to Connection Checkpoint questions are available on
the faculty resources site. Please consult with your instructor.
Pharmacotherapy of Erectile Glans
Dysfunction penis
71.6 Erectile dysfunction is a common disorder Figure 71.2 Anatomy of the penis.
that may be successfully treated with inhibitors
of the enzyme phosphodiesterase-5. occlusion of the veins that drain blood from the corpora,
allowing the penis to remain rigid long enough for suc-
Erectile dysfunction (ED) is defined as the consistent cessful coitus. When stimulation ends or after ejaculation,
inability to either attain an erection or to sustain an erec- cGMP is removed by the enzyme phosphodiesterase-5
tion long enough to achieve satisfactory sexual intercourse. (PDE-5). At this point, the pressure in the penis decreases,
Impotence, a term often used interchangeably with ED, is the veins dilate, blood leaves the corpora, and the penis
the total inability to achieve an erection, an inconsistent quickly loses its rigidity. The anatomy of the penis is illus-
ability to achieve an erection, or the ability to have only trated in Figure 71.2.
brief erections. An estimated 15 to 30 million men in the
United States have ED. The incidence of ED increases with Organic causes of ED may include damage to the
age, although it may occur in men of any age. nerves serving the penis or a decrease in blood flow
through the blood vessels involved in the erection reflex.
Penile erection is a complex event that has psycho- Many chronic illnesses have the potential to damage the
logic, neuromuscular, and vascular components. Sexual arteries, smooth muscle, and fibrous tissues of the penis,
arousal results in the release of neurotransmitters, primar- most notably atherosclerosis, diabetes, stroke, kidney dis-
ily nitric oxide and epinephrine, from the hypothalamus. ease, and HTN. Psychogenic causes may include depres-
This stimulation along the autonomic nerves results in the sion, fatigue, stress, or fear of sexual failure. In some men,
release of an enzyme that makes cyclic guanosine mono- a number of common drugs cause impotence as an adverse
phosphate (cGMP). cGMP causes dilation of the arterioles effect, including thiazide diuretics, phenothiazines, selec-
leading to the major erectile tissues of the penis, called the tive serotonin reuptake inhibitors (SSRIs), tricyclic antide-
corpora cavernosa. Rigidity of the penis results when the pressants (TCAs), propranolol (Inderal), and diazepam
increased local blood flow and pressure fill the vascular (Valium). Another potential cause of ED is hypogonadism,
spaces within the corpora. This engorgement causes
Chapter 71 Drugs for Disorders and Conditions of the Male Reproductive System 1317
Table 71.3 Drugs for Erectile Dysfunction
Drug Route and Adult Dose (Maximum Dose Where Indicated) Adverse Effects
avanafil (Stendra) PO: 100 mg approximately 30 min before intercourse (max: 200 mg Nasal congestion, headache, facial flushing,
once/day) dizziness, vision abnormalities, myalgia
sildenafil (Viagra) PO: 25–50 mg approximately 30–60 min before intercourse (max: Hypotension when taken with nitrates, priapism,
100 mg once/day) hearing loss, nonarteritic anterior ischemic optic
neuropathy
tadalafil (Cialis) PO: 10 mg approximately 30 min before intercourse
(max: 20 mg/day); once-daily dosing: 2.5–5 mg daily
vardenafil (Levitra, Staxyn ODT) PO: 10 mg approximately 1 h before intercourse
(max: 20 mg once/day)
Note: Italics indicate common adverse effects. Underline indicates serious adverse effects.
which can cause an inability to develop an erection, owing adverse effects are similar. The most common adverse
to the loss of libido. Nerve innervation and blood flow to effects are nasal congestion, headache, facial flushing, and
the penis may be damaged by surgery, particularly during dizziness. These drugs produce a 5- to 10-mm fall in blood
procedures involving the prostate gland. pressure, but this drop is usually not clinically important.
In patients who are taking nitrates or multiple antihyper-
A thorough health history of male patients should tensive medications, however, this blood pressure change
include questions regarding sexual function. Laboratory may produce symptoms of hypotension. Therefore, PDE-5
tests to check for possible metabolic or hormonal causes of inhibitors are contraindicated in patients who are taking
ED include serum testosterone, prostate-specific antigen organic nitrates in any form. Organic nitrates include nitro-
(PSA), blood chemistries, and prolactin and thyroxin lev- glycerin and isosorbide mononitrate.
els. A nocturnal penile tumescence and rigidity (NPTR) test
may be ordered. This test monitors the number of erections Alprostadil (Caverject, Edex, Muse) is an alternative for
during sleep and is used to differentiate between the psy- men who have contraindications to the use of PDE-5 inhibi-
chologic and physiologic causes of ED. A penile blood flow tors. Caverject and Edex formulations are self-injected
test is also used to determine whether there is sufficient directly into the corpora cavernosa just prior to intercourse.
arterial and venous flow through the penis. Patients who Muse is a pellet containing the drug that is inserted by an
have diminished or abnormal blood flow may find that the applicator into the urethra just prior to intercourse. Alprosta-
drugs used to treat ED are not effective. These patients may dil by either method should not be used more than 3 times
have more success with penile implants. per week and not more than once in 24 hours. Penile pain,
burning sensations, and priapism are common adverse
The treatment of ED is becoming more prevalent as the effects and, more rarely, penile fibrosis. The effectiveness of
population ages because more men are becoming affected alprostadil is less than that of the PDE-5 inhibitors or intra-
by the disorder. If hormones are the cause of the dysfunc- cavernosal injections, and the strength of the erection can be
tion, treatment is aimed at correcting the abnormality. In improved by using a constriction ring.
some, testosterone replacement therapy by IM injection or
transdermal patches may assist with ED, particularly if PROTOTYPE DRUG Sildenafil (Viagra)
associated with hypogonadism or low libido. If the cause is
found to be psychologic, treatment will usually consist of a Classification Therapeutic: Drug for treating impotence
combination of psychotherapy and pharmacotherapy. Pharmacologic: Phosphodiesterase-5
The approval of sildenafil (Viagra), the first PDE-5 inhibitor
inhibitor, revolutionized the treatment of ED. Three other
PDE-5 inhibitors have since been approved by the FDA: Therapeutic Effects and Uses: Approved in 1998,
avanafil (Stendra), vardenafil (Levitra, Staxyn), and sildenafil is a PO drug and was the first PDE-5 inhibitor
tadalafil (Cialis). Drugs for ED are listed in Table 71.3. approved for ED. The onset of action is relatively rapid
(less than 1 hour), and its effects last up to 4 hours.
The PDE-5 inhibitors do not cause an erection. They
merely enhance the erection resulting from physical con- In 2005, sildenafil (Revatio) was approved for the treat-
tact or other sexual stimuli by maintaining relaxation of the ment of pulmonary arterial HTN. For this indication, block-
smooth muscle in the penis and increasing blood flow. ing PDE-5 in pulmonary vascular smooth muscle causes
These drugs are not as effective in promoting erections in vasodilation and reduction in arterial HTN. The drug
men who do not have ED. Despite considerable research improves exercise capacity in these patients. The dosing for
interest, PDE-5 inhibitors have no effects on female sexual Revatio is 5 to 20 mg three times daily. Off-label indications
function. These drugs are not approved for use by women. include prevention of pulmonary HTN induced by altitude
sickness and treatment of Raynaud’s phenomena resistant
The PDE-5 inhibitors are equally effective at promot- to vasodilator therapy.
ing erections in 60% to 80% of male patients, and the
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