Endometriosis

Disease State Management | Endometriosis 1

ENDOMETRIOSIS

LINDSY JEAN O. PALABRICA | DOCTOR OF PHARMACY
OBJECTIVES
At the end of the report the students/readers should be able to:

 Define what is Endometriosis
 Understand the etiology and pathophysiology of Endometriosis
 Identify the signs and symptoms of Endometriosis as to the location of implants.
 Determine proper treatment plan including pharmacologic and non-pharmacologic therapy.
 Give proper patient education

WHAT IS ENDOMETRIOSIS? ENDOMETRIOMAS “Chocolate Cysts”
Presence of endometrial tissues in the ovaries and is the
Endometriosis is an inflammatory, estrogen dependent most common form of endometriosis. During menstrual
condition associated with pelvic pain and infertility. It is an shedding and bleeding of endometrial implants due to
aberrant growth of endometrial glands and stroma changes of hormone level and chronic inflammation, it
(endometrium) outside the uterus (pelvis, fallopian tubes, causes a gradual invagination of the ovarian cortex which
cervix, vagina, ovaries, bladder and colon) and is the most results in a pseudocyst. The cyst contains the old dark blood
common cause of dysmenorrhea and chronic pelvic pain in and shed tissues. When these implants become too large, it
women (associated with infertility). will rupture and spill their contents which results in pain and
more inflammation.
Endometrium – the tissue lining the inner cavity of the uterus which
thickens during menstrual cycle; consist of a single layer of columnar Stages of Endometriosis | Minimal, Mild, Moderate, Severe
The most widely used scale to measure endometriosis is
epithelium plus stroma on which it rests. from the American Society of Reproductive Medicine. Points
are assigned according to the spread of endometrial tissues,
Figure 1: Anatomy of female reproductive organ its depth, and the areas of your body that are affected.

Endometriotic growths/ endometriosis implants are benign Stage 1 (Minimal) Stage 2 (Mild)
and non-cancerous. These implants have the same  Small implants, wounds or  > implants than in stage 1;
hormonal cycle and same estrogen receptors as normal
endometrial tissue so they go through with the same lesions deeper in the tissue
proliferation, secretion and menstruation cycle which  Found on your organs or  Some scar tissue
causes inflammation, scarring, adhesions, and
endometriomas. the tissue lining your

2 Key differences between Normal Endometrial cells and pelvis or abdomen
Endometriosis Implants:  Little to no scar tissue

1. Implanted cells contain HIGH LEVELS of enzyme Stage 3(Moderate) Stage 4(Severe)
AROMATASE which allows them to produce their  Many Deep Implants  Most widespread
own estrogens.  Have small cysts on one or  Many deep implants and

2. Implanted cells release PRO-INFLAMMATORY both ovaries thick adhesions
FACTORS which causes inflammation and scarring.  Presence of adhesion  Large cysts on both
These scars cause adhesions, which binds organs and
structures together affecting their anatomical (thick bands of scar ovaries
placement.
tissues)
Estrogens and Pro-inflammatory factors both promote the
growth of new blood vessels which nourishes the implants. EPIDEMIOLOGY

The prevalence of endometriosis in the general population
is estimated to be 5% to 10% of women. Up to 70% of adult
women and up to 50% of adolescents presenting with
chronic pelvic pain may have endometriosis, and ~20% to
50% of women with infertility may have the disorder.

In the Philippines, it is prevalent in 10%-15% of women in
the reproductive age group. Also it is the major cause of
chronic pelvic pain in 33% of women.

Disease State Management | Endometriosis 2

ETIOLOGY CLINICAL PRESENTATION | SIGNS & SYMPTOMS

The etiology of endometriosis is still unknown but there are All these symptoms often vary with the hormone changes throughout the
5 main theories as to why some women develop
endometriosis and these are: menstrual cycle and worsen during periods.

a. Retrograde Menstruation Theory – during menstruation Conscious pain mapping (with the patient awake) has been
some blood carrying endometrial cells will flow used to locate the specific areas that cause pain.
backward into the fallopian tubes and implant into the
nearby tissues. There could also be a tubal patency which Table 1: Signs of Endometriosis
means that the fallopian tubes are open and the
adventurous endometrial cells could escape and travel Symptoms of endometriosis can be variable but typically
to other sites such as the pelvic and abdominal reflect the area of involvement. Such symptoms may include
structures. the following:

b. Immunologic Changes – dysfunction with the immune Reproductive Pelvic Pain Dysmenorrhea
system; Findings of abnormal B- and T-cell function in
which they don’t respond to the endometrial implants Organs Bleeding Dyspareunia
and allow it to grow, decreased apoptosis, and altered
levels of prostanoids, cytokines, growth factors, Pouch of Douglas Dyschezia (Pain with
interleukins, and aromatase in endometrial lesions and
peritoneal fluid of affected women. defacation)

c. Metaplastic Theory ( Coelomic Metaplasia) – the cells of Bladder Urgent, frequent, and Painful
peritoneum come from the same cell line as with the
endometrial cells and can transform spontaneously into urination
endometrial tissue (changing from one normal type of
tissue to another normal type of tissue). Intestines Abdominal Pain

d. Benign Metastases Theory – endometrial cells can travel Table 2: Symptoms vary on the location of endometrial cells
to distant organs to the lymph and blood.

e. Extrauterine Stem Cell Theory – stems cells in the bone
marrow differentiate into endometrial cells and then
travel into other parts of the body.

PATHOPHYSIOLOGY | PAIN & INFERTILITY DIAGNOSIS

Ectopic endometrial tissues are most commonly located in Definitive diagnosis can only be made by direct surgical
the dependent portions of the female pelvis (posterior and visualization of endometrial lesions. Laparoscopy is the gold
anterior cul-de-sac, uterosacral ligaments, tubes, ovaries), standard investigation, unless disease is visible in the vagina
but any organ system is potentially at risk. or elsewhere.

Endometriosis Associated Pain Laboratory Test
Secondary to generation of local inflammation by the  Valuable in diagnosing Endometriosis; helpful in ruling
endometrial lesions, bleeding from the endometrial tissues,
and irritation or compression of nerve fibers by endometrial out specific conditions (Appendicitis, Chlamydia, UTI,
tissues. Also, estrogen has been found out to contribute to Cystitis, Diverticulitis, Ectopic Pregnancy, Gonorrhea,
endometriosis pain due to its role in helping to produce Ovarian Cyst, PID)
endometrial tissues and in stimulating the release of
inflammatory substances. a. CBC – may help differentiate pelvic infecton from
endometriosis as well as the degree os blood loss.
Endometriosis Associated Infertility
The exact mechanism by which endometriosis reduces b. Urinalysis and Urine Culture – help to rule out UTI;
fertility is still unknown, but it may result from distorted Gram stain and culture should be considered to
pelvic anatomy, altered peritoneal function and altered rule out STD.
endometrial receptivity that impairs implantation.

Disease State Management | Endometriosis 3

Ultrasonography (Transvaginal or Endorectal) Combined Hormonal Contraceptives (CHCs)
 The ultrasonographic features of endometriomas vary  Treat the pain of endometriosis by decreasing menstrual

from simple cysts to complex cysts with internal echoes flow and regressing endometrial implants.
to solid masses usually devoid of vascularity.  Prevents ovulation by the combination of Estrogen and
 Transvaginal Ultrasonography identifies the classic
Chocolate Cyst of the ovary. Progesterone which creates a synergistic effect that
increases antigonadotropic and ovulation inhibitory
MRI and CT scan effect.
 Magnetic Resonance Imaging (MRI) is helpful in  Combined Oral Contraceptive Pills (Yaz, Yasmin, Diane),
Contraceptive Patch (Ortho-Evra), Contraceptive Vaginal
detecting rectal involvement and has been shown to Ring (Nuva Ring)
accurately detect rectovaginal endometriosis and cul-de-
sac obliteration; ultrasonographic gel was inserted in the Progesterone
vagina and rectum.  Progestin – a form of progesterone; synthetic. Interact
 Computed Tomography (CT) Scanning – Endometriomas
may appear as cystic masses but their appearance is with progesterone receptors in the body in order to
nonspecific. cause progesterone like effects.
 Medroxyprogesterone acetate (MPA) & Levonorgestrel
Laparoscopy and Biopsy (LNG) - progesterone analogues which inhibits the
 Laparoscopy is considered the gold standard growth of endometrium.
 MPA – inhibits secretions of gonadotropin from pituitary
investigation for endometriosis. gland and prevents follicular maturation and ovulation.
 Histologic demonstration of both endometrial glands  LNG – known as Plan B; used for ovarian suppression to
help improve symptoms of endometriosis.
and stroma in biopsy specimens obtained from outside
the uterine cavity is required to make the diagnosis of Danazol
endometriosis.  A synthetic steroid analogue of 17-ethinyl testosterone.

TREATMENT AND MEDICATIONS It induces anovulation, amenorrhea, and endometrial
atrophy through pituitary suppression of the midcycle LH
The goals of endometriosis treatment are: and FSH surge and induction of a high-androgen, low-
a. Removal of endometrial deposits estrogen environment.
b. Prevention of disease progression  Formerly the “gold standard” of endometriosis
c. Minimize pain treatment but no longer consider due to its side effects.
d. Prevention or correction of associated infertility
Gonadotropin Releasing Hormone (GnRH) agonist
Guideline recommend empirical treatment of chronic pelvic  Create a functional oophorectomy via inhibition of
pain suspected to be secondary to endometriosis with
follicle-stimulating hormone (FSH) and luteinizing
combined contraceptives (CHCs) or progestin for at least 3 hormone (LH) secretion which in turn diminishes
months. endometrial pain. It decreases level of estrogen.
 Goserelin, Leuprolide, and Nafarelin differ by route of
administration.

Pharmacologic Therapy Nonsteroidal Anti-inflammatory Drugs (NSAIDs)
Pharmacologic therapy is the first choice for treatment of  Effective first line of treatment in managing pain caused
endometriosis-related pain to minimize risks from surgery.
However, drug therapy will not treat endometriosis-related by endometriosis.
infertility.  Ibuprofen, Naproxen

Mainstay Medical Treatment: Aromatase Inhibitors
 Suppresses estrogen synthesis in the ovaries.
These treatments have similar clinical efficacy in terms of  Inhibits aromatase enzyme (converts androgens into
reduction in pain-related symptoms and duration of relief
 Combined Hormonal Contraceptives (CHCs) estrogens).
 Progestin (Synthetic Progesterone)  Reduces inflammation and pelvic pain
 Danazol  Anaztrazole, Letrozole
 Gonadotropin Releasing Hormone (GnRH)

Disease State Management | Endometriosis 4

For Endometriosis – related pain, it should be relieved within 2 month and low fat dairy products. Also include green leafy
of initiating medical therapy. If symptoms persist consideration should vegetables, legumes, berries, and fruits that are
high in antioxidants.
be given to different medical practitioner and or consider surgical  Nutrients. Focus on key nutrients. Foods rich in
therapy. vitamin B, iron rich foods, omega fatty acids, fiber.
 Water. Drink plenty of water instead of coffee and
For Endometriosis – related infertility, 6 months of watchful waiting alcohol, it will make your pain worse.
after surgical intervention. If pregnancy is not achieved within that  Warm bath. It will help relieve endometriosis pain.

time, consider reproductive technique. REFERENCES
Pharmacotherapy: A Pathophysiologic Approach 8th Edition;
Nonpharmacologic Therapy | Surgical Intervention Dipiro, JT, et.al, 2011
Surgical intervention can be classified into: Conservative, Pathogenesis and Pathophysiology of Endometriosis;
Semiconservative, and Radical Surgery. Richard O. Burney, M.D., M.Sc. and Linda C. Giudice, M.D.,
Ph.D.; September 2012
Laparoscopy - used in endometriosis as both a diagnostic Everyday Health: Can a Sitz Bath Help Ease Endometriosis
and a therapeutic tool, and guidelines recommend removal Pain? By Landau, MD.; September 2018
of visible lesions at the time of initial diagnosis Lippincott illustrated Reviews Pharmacology 6th Edition;
Karen Whalen, PharmD, BCPS, et.al; 2015
Conservative Surgery https://www.rcog.org.uk/en/patients/patient-
 When reproductive potential is retained leaflets/endometriosis/
 Destroy visible endometriotic implants and lyse peritubal https://emedicine.medscape.com/article/271899-
treatment#d13
and periovarian adhesions. https://www.webmd.com/women/endometriosis/endomet
 Laparoscopic approach is the method of choice for riosis-types-stages#2
https://emedicine.medscape.com/article/271899-overview
treating endometriosis conservatively.

Laparoscopic ablative surgery with bipolar diathermy or laser for
endometriomas was shown to be effective for relieving pelvic
pain in 87% of patients.

Semiconservative Surgery
 Reproductive ability is eliminated but ovarian function is

retained.
 This surgery involves hysterectomy and cytoreduction of

pelvic endometriosis.

Radical Surgery
 Uterus and ovaries are removed.
 Involves total hysterectomy, bilateral salphingo-

oophorectomy (TAH-BSO) and cytoreduction of visible

endometriosis.
 Adhesiolysis is performed to restore mobility and normal

intrapelvic organ relationships.

PATIENT COUNSELLING
 Endometriosis is progressive and can result in

chronic pain and infertility. Gynecologic follow up

is advised.
 Exercise. May help improve your wellbeing and

may help to improve some symptoms of

endometriosis.
 Psychological therapies and counselling.
 Diet. Cut out certain food that may worsen the

symptoms. Certain foods that may help lessen the

pain includes: food rich in protein such as fish, eggs,