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Symptom resolution after operative

e Cambridge Core terms of use, available at
.008

Chapter Pelvic Pain Arising from Endometriosis

8 Mark Dassel and Alyssa Herrmann

Editor’s Introduction Introduction

Endometriosis is the most common gynecological Endometriosis is a common cause of pelvic pain,
condition leading to pelvic pain and often it is the affecting an estimated 10% to 15% of women of repro-
only one recognized by gynecologists. In many ductive age [1]. The disease has been associated with
cases it coexists with pelvic floor muscle spasm, 70% of women who present to chronic pelvic pain
interstitial cystitis/bladder pain syndrome and clinics [2] and about 50% of all infertility patients [3].
irritable bowel syndrome and often all four are Despite its high prevalence, treatment methodologies for
grouped as “evil quadruplets.” Endometriosis can endometriosis remain controversial, even as the cannon
be diagnosed only surgically; and pathology of endometriosis literature continues to grow.
confirmed tissue biopsy is by far the most Traditionally, surgical evaluation and treatment of
accurate way of diagnosis. Unfortunately, all endometriosis were the mainstays of treatment; how-
medical treatments of endometriosis are quite ever, pain symptomatology associated with endomet-
inadequate because they all rely on causing riosis is increasingly recognized as a syndrome of
a hypoestrogenic state that only provides painful conditions rather than a single pain etiology
temporary relief of pain, and soon after to be corrected surgically. This greater recognition of
medication is discontinued, symptoms return. comorbid disease states as (secondary pain gener-
Development of drugs addressing the cause of the ators) is providing a much better understanding of
disease is currently not possible because the cause the etiology of pain associated with endometriosis and
of the disease is unknown. Multiple existing guiding less invasive and more effective treatment
theories fail to unify an explanation of all cases, options.
leading to the possibility that different etiologies
may lead to a presence of endometrial glands and In this chapter we will address the link between
stroma in the peritoneal cavity and outside. endometriosis and pain symptomatology including
Surgical resection of endometriosis in skilled the ways that different types of endometriosis lead to
hands is effective but patients need to be pain symptoms. Furthermore, we will evaluate surgi-
informed that disease will most likely return within cal and nonsurgical techniques that have been shown
a few years of initial surgery. Deep infiltrating useful in the treatment of endometriosis-related pain.
endometriosis requires a very knowledgeable
surgeon and often a specialized center for Endometriosis is broadly defined as the presence of
treatment. Additional procedures such as presacral endometrioid glands and stroma ectopic to the uterus.
neurectomy, although controversial and This definition, though histologically accurate, does
potentially risky, may alleviate dysmenorrhea not fully describe the link between endometriosis
symptoms in some patients. Meticulous removal of and associated painful symptoms. Furthermore, endo-
ovarian endometriomas is a must in all infertility metriosis does not present as a singular phenotype;
patients and most pelvic pain patients as simple rather it presents in varied tissue architectures. There
drainage will result in almost immediate return of are superficial peritoneal blebs (superficial endometri-
endometrioma. Pre and postsurgical treatment osis), cystic lesions (endometriomas), and large fibrous
with hormonal suppression is still debatable, and nodules (deep infiltrating endometriotic nodules). The
there is research to support it and research architecture of each endometriosis subtype dictates its
showing it ineffective. In my practice I do not use own unique pain signature. Endometriosis subtypes
pre- and postsurgical hormonal suppression. can present in isolation or in combination with one

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.009

Mark Dassel and Alyssa Herrmann

another. As such, each patient’s endometriosis disease marks, and blister-like pustules. Though the varied
must be evaluated and treated as a unique constella- appearance of each of these lesions is not completely
tion of lesion subtypes. Further complicating pain understood in terms of etiology and clinical signifi-
resolution is the myriad of associated, downstream cance, the difference of appearance is likely due to the
pain sequelae. These secondary pain generators are age and activity of the individual lesions [4].
further described in this book and are commonly Technically speaking, a lesion is considered to be
a reaction to the pain in the pelvis created by endo- superficial endometriosis when it histologically con-
metriosis. Frequently encountered secondary pain tains endometrioid glands and stroma and does not
generators are pelvic floor tension myalgia, abdominal invade >5 mm into the surface on which it is attached.
myofascial pain, vulvodynia, and centralized pain syn- It is not possible to know for sure the depth of an
dromes (irritable bowel syndrome, interstitial cystitis/ endometriosis lesion by mere appearance, as studies
bladder pain syndrome). Downstream sequelae of have shown that up to 15% of lesions thought to be
unchecked painful symptomatology can further lead superficial invade >5 mm, making them technically
to depression, anxiety, catastrophizing, and chronic deep infiltrating endometriotic lesions [5].
widespread pain syndromes.
The etiology of superficial endometriosis is not
Recognizing the link between endometriosis sub- beyond debate. Sampson’s theory on endometriosis
types and their accompanying pain syndromes is of is the most widely accepted and appears to best
vital importance in developing a plan to adequately describe superficial endometriosis. It states that reflux
address the complex milieu that defines pelvic pain menstruation causes products of the menstrual cycle
arising from endometriosis. It is no longer acceptable to spill into the peritoneal cavity. This ectopic tissue,
to measure endometriosis cure rates solely by the aided by the natural counterclockwise flow of periton-
absence of lesions in the pelvis at the time of surgery. eal fluid, travels and attaches to peritoneal surfaces
True successful treatment of endometriosis should be within the abdomen and pelvis. Evidence of this reflux
measured by control of the disease itself as well as menstruation has been described in women with and
correction of its downstream sequelae. without endometriosis, indicating reflux menstru-
ation is a common occurrence. The reason some
Subtypes of Endometriosis women develop endometriosis and others do not is
believed to be related to a complex interplay of the
Superficial Endometriosis intraperitoneal immune system, hormonal milieu,
Superficial endometriosis is the most common sub- and the endometrial cells themselves.
type of endometriosis and is most commonly found in
the pelvis (Figure 8.1). It can present as dark purple- Cystic Endometriosis
blue blebs, deep red splinter hemorrhages, gunpowder
Cystic endometriosis, commonly known as endome-
Figure 8.1 Superficial endometriosis. trioma, is most commonly associated with the ovarian
cortex. It occurs in 17%–44% of women who carry the
https://www.cambridge.org/core. at 20:21:52, .009 diagnosis of endometriosis [6]. These cysts can range
from subcentimeter intraovarian cystic structures to
large cysts that completely encompass the ovary. They
are typically filled with a thick brown semiviscous
fluid that resembles liquid milk chocolate, hence the
nickname “chocolate cysts.” The cysts themselves are
frequently thin walled and are easily ruptured surgi-
cally, though they rarely grossly rupture spontan-
eously. Quite often, endometriomas are associated
with pelvic adhesive disease, scarring to the pelvic
sidewall, loops of bowel, or posterior cul-de-sac.
Because of their tendency to form as bilateral ovarian
cystic structures (28%)[7], they commonly scar
together in the midline, posterior to the uterus, form-
ing “kissing ovaries.” These adjoined ovaries are

Pelvic Pain Arising from Endometriosis

frequently imbedded deep in the pelvis, scarred to the Figure 8.2 Deep infiltrating rectal nodule.
uterus, bilateral fallopian tubes, or the colon or rec-
tum or both. Their presence can portend deep infil- uterosacral ligament [13]. Because of its proximity to
trating nodules along the uterosacral ligaments, the gastrointestinal tract, this type often invades the
posterior cul-de-sac, or rectovaginal septum. colorectum (Figure 8.2). Other abdomino-pelvic sites
of endometriosis include sites along the ureter, urin-
Endometriomas are thought to have ary bladder, appendix, and diaphragm. Endometriosis
a pathogenesis similar to that of superficial endomet- has also been discovered in remote locations includ-
riosis. Consistent with Sampson’s theory, Hughesdon ing the lungs, heart, brain, and even the ear lobe.
suggested that endometrial cells are refluxed into the Theories suggest that these may be from stem cell
peritoneal cavity. These cells travel to the surface of an rests that formed during embryonic development.
ovary that has just undergone ovulation. The endo- Still other theories suggest a hematogenous or lymph-
metrial cells implant and as the ovarian cortex heals atic spread of endometriosis is possible. The basic
over, thus trapping the endometriotic tissue within science of endometriosis is evolving at a rapid rate,
a superficial cystic structure on the surface of the and further discoveries continue to elucidate the eti-
ovary. These cells are bathed in the ovarian hormonal ology of the complex pathogenesis of this disease and
milieu and begin to cycle as typical endometrium. As its many subtypes.
this tissue is trapped, endometrial debris and blood
products are contained within a cystic structure that Diagnosis of Endometriosis
continues to expand into an endometrioma [8].
In the setting of chronic pelvic pain, establishing
Deep Infiltrating Endometriosis a diagnosis of endometriosis may be important; how-
ever, establishing a definitive diagnosis often requires
Deep infiltrating endometriosis (DIE) is the most surgical intervention, which confers certain risks to
complex form of endometriosis in the way it interacts the patient. Given a physician’s duty to “first do no
with tissues and pelvic organs. While numbers may be harm,” it is important that one weighs the risks and
underreported given the difficulty of diagnosis, as benefits of performing a diagnostic procedure, espe-
many as 20% of patient with endometriosis have cially if diagnosis will not alter management. There
been reported to have DIE [9]. DIE typically presents are certain situations in which surgical intervention
as a thick fibrous nodule that contains smooth muscle will be superior to nonsurgical interventions and thus
tissues, fibroblasts, a fibrous matrix, and characteristic may justify an initial surgical approach. These situ-
endometrial gland and stroma [10]. Because of the ations will be highlighted later in the chapter. Surgery
ability of endometriosis to secrete neural and epithe- should not be the primary therapeutic approach when
lial growth factors, the lesions are rich in blood supply a patient has a high pretest probability of disease and
and neural tissue. The technical definition of deep conservative therapies are likely to be of therapeutic
infiltrating endometriosis is a lesion of endometrioid success. It is, however, important to recognize
glands and stroma that invades >5 mm into its place
of attachment; however, this definition is somewhat 87
antiquated, as the histologic makeup of DIE more
closely resembles adenomyosis than just a deeper
invading form of superficial endometriosis lesion
[11]. Interestingly, when DIE was primarily described
by Karl von Rokitansky in 1860, it was termed “ade-
nomyosis externa” because it contained endometrial
tissue associated with extensive fibromuscular and
loose connective tissue elements [12], resembling
our current understanding of adenomyosis. This indi-
cates that our increased understanding of endometri-
osis today may be leading back to the origins of its
diagnosis.

The most common place to find deep infiltrating
endometriosis is at the junction of the uterus and

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Mark Dassel and Alyssa Herrmann

histology from directed biopsy is the gold standard in Table 8.1 Important anatomy to evaluate during diagnostic
the diagnosis of endometriosis. Other diagnostics laparoscopy for endometriosis
tests including imaging and serum blood tests have
proven disappointing in the definitive diagnosis of Anterior cul de sac
endometriosis; however, some subtypes of endomet-
riosis are more easily discernible with certain methods Posterior cul de sac
than others.
Left ovarian fossa
Superficial Endometriosis
Right ovarian fossa
Currently, neither serum blood testing nor imaging
can successfully diagnose superficial endometriosis. Bilateral fallopian tubes and ovaries
Ultrasound, CT, and MRI do not have the fidelity to
identify small, subcentimeter peritoneal lesions of Uterus
superficial endometriosis. These modalities can occa-
sionally identify coexisting intraabdominal adhesive Uterosacral ligaments
disease that can suggest the diagnosis, but since exten-
sive scarring seems to occur with less frequency among Appendix
isolated superficial endometriosis, these noninvasive
imaging techniques are nonspecific. Blood tests to Colon and rectum
date have been shown to be ineffective in the diagnosis
of superficial endometriosis, though CA-125 Diaphragm (both left and right sides)
a nonspecific marker of intraperitoneal inflammation,
will often be elevated when endometriosis is present. From a physical exam standpoint, superficial
endometriosis in isolation can be difficult to diagnose.
Apart from a surgical diagnosis, the most effective There are no palpable lesions to confirm diagnosis;
tool for diagnosis of endometriosis comes from the however, one can infer the presence of superficial
history and physical exam. The most common symp- endometriosis when retrocervical tenderness is pre-
toms in women with endometriosis are dysmenorrhea sent on bimanual exam. Similarly, DIE can also lead to
and dyspareunia. Dysmenorrhea is typically present this finding.
from the first few menstrual periods in a woman’s
reproductive lifecycle or sometime later in the teenage As previously mentioned, the gold standard in
years. Differentiating pathologically painful periods diagnosis of endometriosis is histological, which
from the typical period cramping can be difficult. It is means a sample needs to be surgically collected. For
important to ask patients about painful menses, as many diagnosis, it is important that endometriosis lesions
women think the pain they experience is normal and be both directly visualized and biopsied, as visual
may not report concerns without prompting. A typical identification of lesions alone can lead to a false-
differentiating factor is whether periods are painful positive diagnosis [4]. Furthermore, it is important
enough to cause a patient to stay home from work or that a full survey of the abdomen and pelvis be com-
school. Additionally, young women with endometriosis pleted and fully documented in the operative report.
may have more abnormal bleeding cycles than age- This level of detail ensures that future practitioners
matched controls [14]. Dyspareunia is a common com- will have the confidence that a full evaluation of the
plaint in women with superficial endometriosis as well. abdomen and pelvis was completed to rule out endo-
This is sometimes linked to endometriosis at the junc- metriosis. The areas of the pelvis that should be sep-
tion of the uterus and the cervix, resulting in an area of arately visualized and commented on are in Table 8.1.
tenderness that may be struck on deep insertion during
intercourse. This pain is termed deep thrust dyspareunia Endometrioma
and should be differentiated from entry dyspareunia.
Alternatively, entry and deep thrust dyspareunia can The diagnosis of endometrioma is typically less enig-
develop as part of the sequelae of endometriosis- matic than superficial endometriosis because it typic-
related pain, for example, in cases of vulvodynia or ally presents as a cystic structure with characteristics
pelvic floor tension myalgia. findings on various imaging modalities. Pelvic ultra-
sound and MRI can both be employed to discern the
e Cambridge Core terms of use, available at etiology of an endometriotic cyst to a limited degree of
.009 efficacy. While an endometrioma has specific features
on each of these modalities, it can appear similar to the
hemorrhagic corpus luteal cyst, a common, nonpatho-
logical, self-limited finding. Persistence of a mass and
clinical correlation to tenderness on bimanual exam
are important adjunct findings to aid in the diagnosis

Pelvic Pain Arising from Endometriosis

of endometriomas. Malignancy must also be con- a diagnosis of DIE, though specificity can be high
sidered when a complex cystic structure is present with certain findings on physical exam, ultrasound,
and should be included in the differential and MRI. As with other subtypes of endometriosis,
diagnosis. sensitivity of detection techniques is lacking in many
cases. Colonoscopy has long been suggested to be an
Symptomatology effective tool in the diagnosis of deep endometriosis,
but studies have shown it to be of very little utility in
Women with endometriomas tend to develop more detecting DIE of the bowel.
noncyclic pelvic pain than those with superficial
endometriosis alone. Frequently pain develops Because of the high cost of advanced imaging in
semiacutely and persists as the tender cyst grows endometriosis, the history and physical exam are very
and leads to increased mass effect. This pattern of important in aiding diagnosis. A thorough history
slowly increasing pelvic pain not directly associated and physical examination can modify the pretest
with menses may be easily confused with the devel- probability of finding DIE on imaging, allowing the
opment of pelvic floor tension myalgia, which also practitioner to be judicious with testing. Patients with
tends to lead to increased noncyclic point tender- DIE frequently display organ-specific dysfunction.
ness on contact such as is present with intercourse. DIE that involves the bowel can cause increased pain
Fortunately, these etiologies can be differentiated with defecation, increasingly intense dysmenorrhea,
with physical exam and imaging. A pelvic exam and deep thrust dyspareunia [16] as well as constipa-
that demonstrates a painful mass or adnexal tender- tion and rarely narrow-caliber stools. Similarly, DIE
ness that reproduces painful symptoms suggests the of the bladder often presents with higher rates of
presence of endometrioma, which is not seen in urinary urgency, frequency, and hematuria. Patients
hemorrhagic corpus luteal cysts. It is also important with DIE often complain of point tenderness at the
to examine the pelvic floor musculature in these sites of endometriotic nodules. For example, uterosa-
cases. Isolated tenderness of the pelvic floor (espe- cral ligament endometriosis commonly presents as
cially that reproduces the patient’s pain) may indi- deep thrust dyspareunia, specific to certain position-
cate that the pain is due solely to pelvic floor ing during intercourse. Pain is frequently reprodu-
tension myalgia or dysfunction. When this test is cible on physical exam with palpation of the nodule
equivocal ultrasound or MRI diagnosis can be help- [17].
ful. We find that the information obtained from an
exam for adnexal tenderness is most helpful when Physical exam findings with DIE can be quite
trying to decide whether to repeat imaging to estab- impressive; often thick rubbery tissue is palpated on
lish persistence of a mass or whether to move to physical exam. Retrocervical nodules can be dis-
surgery more expeditiously. covered along the uterosacral ligaments or along the
bowel and are often described as uterosacral ligament
Ultrasound and MRI nodularity. More rarely, an examiner may find tender
nodularity in the inguinal fold or along the abdominal
MRI sensitivity and specificity are just slightly bet- wall [17].
ter than ultrasound in the diagnosis of endome-
trioma [15]. Given the ability to further Ultrasound and MRI
characterize cysts, MRI should be considered when
transvaginal ultrasound (TVUS) is inconclusive or Proper characterization of DIE is important, espe-
with concern for malignant transformation. MRI cially preoperatively. It is important to be able to
imaging with contrast enhancement should be util- properly counsel patients about steps that may need
ized if question regarding potential neoplasm to be taken to partially or completely remove endo-
remains. metriotic lesions found intraoperatively. Abrao et al.
demonstrated a sensitivity and specificity of 98% and
Deep Infiltrating Endometriosis 100% in TVUS for deep infiltrating endometriosis
[13]. Given this accuracy, low cost, and ease of test,
Diagnosis of DIE is more complex than the diagnosis TVUS is the recommended initial test for those
of superficial endometriosis or endometrioma. No patients with suspected endometriosis, however,
one methodology can definitively establish with the important caveat that the ultrasonographer
is well versed in the identification of endometriosis.
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Figure 8.3 Bowel endometriosis on MRI. obliteration of its sequelae including pain, subfertility,
and organ dysfunction as they relate to overall quality
Unfortunately, this level of expertise currently exists of life.
in only a few centers around the world. Additional
methods, such as tender-point guided ultrasound, Focused treatment strategies of endometriotic
where attention is focused on areas previously found lesions fall into two general categories: medical treat-
to be tender on physical exam, can increase diagnosis ment with the use of chemical compounds to suppress
of endometriosis with TVUS [18]. and diminish endometriosis and surgical manage-
ment with the goal of destruction or resection of
MRI is also well studied as an imaging modality endometriotic lesions. Medical strategies include the
for the diagnosis of endometriosis (Figure 8.3). It has induction of amenorrhea and suppression of disease
been shown that the sensitivity and specificity of MRI through altering the hormonal milieu involved in
is 83% and 98% respectively for those patients with menstrual cycle regulation. Destruction and dimin-
DIE[13]. MRI should be considered as a follow-up ution of lesions can be accomplished by halting the
form of imaging in cases in which TVUS is equivocal. release and creation of hormones essential to endo-
This is also true in patients who are symptomatic with metriosis growth and menstrual cycle regulation.
negative ultrasound findings. MRI has also been Surgical management focuses directly on destruction
found to improve diagnosis of endometriosis in of lesions through fulguration and resection with
areas difficult to visualize with TVUS including the a secondary goal of restoring normal anatomy by
rectovaginal septum. resolving and removing endometriosis-associated
scar tissue.
Treatment Options for Endometriosis
Subtypes Specific Treatments for Superficial
Endometriosis
The variety of treatments of endometriosis are as
broadly differing as the subtypes and presentations of Superficial endometriosis is generally responsive to
the disease itself. All subtypes of endometriosis (includ- both medical and surgical management, each with
ing superficial, cystic, deep infiltrating; and more rare distinct advantages and disadvantages. Medical man-
subtypes such as abdominal wall and catamenial endo- agement of endometriosis has the benefit of being
metriosis) require lesion-specific treatment planning. noninvasive; however, many of the agents used may
Importantly, the obliteration of the disease itself must cause significant side effects, and their efficacy does
not be the only treatment goal, as the guiding principle not last long after cessation of use. Surgical treatment
to the treatment of endometriosis should be the exposes the patient to increased risk; however, it may
offer a longer interval of symptomatic relief. The side
effects of surgery are predictable in terms of postop-
erative pain and recovery time; however, the recur-
rence of disease and coexisting pain is quite common.
Focusing on treatment of downstream sequelae of
endometriosis postsurgically is advantageous in slow-
ing the recurrence of painful symptomatology.
Postoperative menstrual suppressive therapy may be
indicated. Furthermore, in choosing between medical
and surgical management, a patient’s goals must be
considered with regard to restoration of organ func-
tion and the restoration (or maintenance) of fertility.

There are many medical therapeutic options used
to suppress or neutralize endometriosis. Broadly,
there are medications that provide gonadotropin hor-
mone stabilization or suppression of gonadotropin
production and release. In both cases the mainstay
of treatment is menstrual suppression preventing cyc-
lic inflammatory changes wrought by active

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Pelvic Pain Arising from Endometriosis

endometriotic lesions. The efficacy of cycle control Complete suppression of the hypothalamic–pitu-
can be measured by the development of induced itary–adrenal axis is also an effective method of indu-
amenorrhea. Effective menstrual suppressive agents cing amenorrhea and suppressing the growth of
are injectable medroxyprogesterone acetate, and the endometriosis. For this reason, medications such as
levonorgestrel IUD, both of which have been studied leuprolide acetate and gestrinone (gonadotropin-
and shown to improve outcomes in pain related to releasing hormone [GnRH] agonists and antagonists,
endometriosis. Further options include combined respectively) are effective in women with superficial
oral contraceptives, intravaginal contraceptive rings, endometriosis. These medications are extremely
and progestin-only treatments such as pills and effective at suppressing menstrual cycles and, there-
implantable progestins. fore, suppressing dysmenorrhea. However, side
effects can preclude their use in some women.
Combined estrogen and progestin contraceptive Common side effects include hot flashes, mood
methods, including the combined oral contracep- changes, vaginal dryness, and other symptoms char-
tive pill and the combined vaginal ring, have been acteristic of estrogen deprivation. Side effects of
shown to reduce endometriosis-associated dysmen- GnRH agonists and antagonists can be partially
orrhea, dyspareunia, and noncyclic pain. As such, attenuated with the use of progestin or estrogen add-
these formulations can be used in both a traditional back therapy. The loss of bone mineral density pre-
(21-day active dose, with 7 days of placebo) and cludes these agents from being used as long-term
a continuous way. This formulation may be espe- therapeutic options in most women. New oral formu-
cially useful in women younger than 40 years of age lations of these medications have shown some recent
who are not breastfeeding who desire oral therapy promise and may have an increased role in the med-
plus effective contraception. Theoretical concerns ical treatment of endometriosis.
exist over the inclusion of estrogen in the treatment
of endometriosis because estrogen is a known Surgical intervention has been well established as
trophic factor for endometriosis lesions in vitro; an effective intervention for endometriosis pain
however, in combination with progestins, studies related to isolated superficial endometriosis.
have supported their use [19]. Their efficacy is likely A Cochrane review of the matter stated laparoscopic
due to overall control of the menstrual cycle, as surgery was associated with decreased pain at both 6
opposed to the regulation of specific sex steroid months (odds ratio [OR] 6.58) and 12 months (OR
hormones. 10.0) compared to those who underwent diagnostic
laparoscopy alone [20]. Furthermore, studies have
Progestin-only formulations have also shown effi- shown that fulguration and resection of endometri-
cacy in the treatment of endometriosis-related pain. osis has proven superior to diagnostic laparoscopy
There is research supporting the use of etonogestrel alone in the resolution of pain. Disagreement still
implants, levonorgestrel IUD, progestogen oral for- exists on whether resection is superior to fulguration;
mulations, and injectable medroxyprogesterone. however, some studies [5] have indicated that resec-
These formulations induce amenorrhea and may tion is more effective. Others have advocated the use
work directly to suppress the growth of endometri- of plasma energy given the ability to control its depth
osis. However, no research to date supports the super- of penetration [16], allowing full fulguration of
iority of progestin-only therapies over combined lesions without damage to underlying structures.
hormonal contraceptives in the treatment of endo- Despite disagreement in methodology, there seems
metriosis-related pain. to be strong evidence that destruction of endometrio-
tic lesions decreases pain symptomatology, especially
Aromatase inhibitors are a unique formulation with regard to dysmenorrhea and dyspareunia.
that may provide benefit in the treatment of endomet- Furthermore, surgical intervention has the added
riosis as well. This therapy, in conjunction with men- benefit of establishing a histologic diagnosis of
strual suppressive therapies, inhibits the peripheral endometriosis.
conversion of androgens to estradiol. This suppresses
menstrual cycles and thereby decreases the amount of Endometrioma
estrogen available for growth of endometriotic
implants. Menopause-like side effects of estrogen Medical treatment has not been proven as effective in
deprivation lead to intolerance of this medication in treatment of cystic endometriosis as it has for isolated
some women.

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Mark Dassel and Alyssa Herrmann

superficial endometriosis. The reason for this, while Still endometrioma remains one of the major indica-
not well understood, is likely multifactorial. tions for surgical intervention in women with endo-
Endometriomas tend to be focally tender, so certain metriosis because of its success with regard to pain
movements such as bending or vaginal penetration relief and preservation of future fertility.
such as in sexual intercourse or pelvic exam can lead
to increased noncyclic pain. Furthermore, mitotic From the resolution of pain, the European Society
activity has been found to be increased in endome- of Human Reproduction and Embryology (ESHRE)
triomas, which may limit regulation of its active glan- recommends surgical resection of endometrioma if
dular tissues by traditional medical therapies. Despite >3 cm in size, with ovarian cystectomy being superior
barriers to medical treatments, there is some evidence to drainage. When an endometrioma is small, it may
of decreasing endometrioma size with medical man- lack suitable planes with the ovarian cortex and
agement; however, medication alone has not been removal may damage the ovary, altering the risk–
shown to resolve endometriomas reliably and benefit analysis of proceeding with ovarian cystec-
completely. tomy [22].

Surgical intervention is the mainstay in the treat- Hormonally mediated suppression of endome-
ment of endometrioma. Drainage, ovarian cystec- trioma recurrence has strong evidence for efficacy
tomy, and oophorectomy have been shown to be compared with other endometriosis subtypes. From
effective in the relief of endometrioma with regard a pathophysiologic standpoint, this is likely due to the
to dyspareunia, noncyclic pelvic pain, and dysmenor- invagination theory of endometrioma formation,
rhea. Deciding which surgical intervention to employ which is contingent on ovulation occurring. From
depends on patient desire for fertility balanced with a practical standpoint, evidence of endometrioma
risk of endometrioma recurrence. The recurrence of suppression is more easily proven because recurrence
endometrioma is understandably lowest in oophorec- can be seen with noninvasive imaging techniques.
tomy. However, most women with endometrioma are Conversely, detection of superficial or deep infiltrat-
of childbearing age, and maintaining the option for ing endometriosis is difficult to detect and may
fertility and the overall health benefits of hormonal require surgical evaluation.
production is important. To this end, ovarian cystec-
tomy has a substantially lower rate of recurrence than Deep Infiltrating Endometriosis
cyst drainage, 15%–40% versus 80%–90%. If suppres-
sive therapy is initiated the postoperatively, the recur- The treatment of deep infiltrating endometriosis
rence rate drops to 8% over a 2-year period [21, 22]. remains quite complex. Interventions differ signifi-
cantly based on lesion location and are determined
Despite higher recurrence rates associated with through risk–benefit analysis on an individual basis.
drainage, it may be preferred in relation to some A major point of decision is the degree to which
fertility outcomes. Endometrioma drainage preserves surgical excision should be pursued, balancing out-
ovarian cortex, making it an attractive option for comes between full excision, partial excision, and
women planning to undergo artificial reproductive suppressive therapies. Risks and benefits of excisional
technologies (ARTs) such as in vitro fertilization surgery vary based on a patient’s pain symptomatol-
(IVF). It has been shown that ovarian cystectomy ogy, degree of organ dysfunction, and the potential of
increases fertility rates compared to nonintervention; complications that may develop. A generally applic-
however, cystectomy may damage native ova. The risk able maxim is that suppressive therapies halt progres-
of ovarian cystectomy in the reproductive population sion of the size of DIE lesions but do not destroy it.
has been illustrated through studies that show Resection is the only definitive treatment for removal
decreased anti-Müllerian hormone (AMH) levels of these thick, fibrous, deeply invasive nodules.
postcystectomy, a marker for ovarian reserve.
However, with follow-up AMH levels have been When resection of DIE proves undesirable, either
shown to rebound to near pre-cystectomy levels. The by patient preference or clinical risk–benefit analysis,
optimal treatment for endometrioma is still debated. medical interventions can be applied. Though hormo-
Many centers support ovarian cystectomy with care- nal agents inducing amenorrhea such as combined
ful preservation of maximum ovarian tissue, while hormonal contraceptives or progestins may suppress
others move to ART prior to surgical intervention. the growth of DIE, efficacy of these medication
remains difficult to establish. Medications that

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Pelvic Pain Arising from Endometriosis

downregulate the hypothalamic–pituitary–adrenal to the high frequency with which it occurs and the
axis, however, such as GnRH agonists and GnRH high impact and frequency of complications that sur-
antagonists have been shown to decrease lesion size. round surgery on the intestinal structures.
This has been associated with a decrease in pain Endometriosis affecting the small intestine is rela-
symptomatology that may recur after cessation of tively rare and will not be discussed in great detail.
treatment.
Some experts suggest that treatment of colorectal
As a result of incomplete resolution of deep infil- endometriosis can be managed conservatively with
trating lesions with medical management, surgical medical management. Largely, treatment with GnRH
intervention is largely considered the mainstay of analogs has proven to shrink deep infiltrating lesions of
therapeutic intervention. Sites most commonly the bowel, decrease organ dysfunction, and decrease
affected by DIE are the uterosacral ligaments, the pain, but perhaps not as fully and reliably as resection
bowel, urinary bladder, ureters, and diaphragm. of the deep lesions. Furthermore, side effects associated
However, growth in distant sites has also been with long-term use of these medications limit their
reported such as pulmonary and neurological sites. functionality as a long-term solution. They are fre-
Furthermore, the iatrogenic spread of endometriosis quently used to decrease nodule size in resective treat-
can cause cystic and deep infiltrating lesions invading ments in an attempt to limit the surgical morbidity.
hysterotomy scars (from caesarean delivery) and
abdominal wall incisions (following both laparotomy Deep infiltrating colorectal endometriosis is gen-
and laparoscopy). The diverse and unique character- erally treated surgically. The bulk of the argument
istics of these lesions require individualized planning among expert endometriosis surgeons centers on
regarding risks and benefits of medical versus surgical the technique for removal of these lesions. Some
intervention, involving the expertise of the physician authors have suggested that shaving of endometri-
and the desires of the patient. osis lesions from the surface of the bowel should be
pursued when possible, only moving toward discoid
Uterosacral Ligament Endometriosis resections and segmental bowel resections upon
deep lesion invasion. Other authors have recom-
The uterosacral ligament is the most common anatom- mended more liberal use of segmental resection to
ical site for the growth of DIE. Its involvement is ensure complete removal of endometriosis that may
recognized clinically as retrocervical tenderness or not be seen except microscopically. Still others have
nodularity. Patients will often report deep thrust dys- recommended the use of plasma technology either
pareunia well localized to lesion location. This pain is in conjunction with or in lieu of these methods. The
commonly reproducible on pelvic examination and is decision regarding which technique of colorectal
typically exquisitely tender to palpation. Imaging studies endometriosis excision to choose is based on the
report that they represent 83% of DIE lesions [13]. completeness of resection, restoration of proper
These lesions are the most common to occur in isolation bowel function, resolution of pain (mainly dysche-
and are frequently adhered to the colorectum but may zia, dyspareunia, and dysmenorrhea), and incidence
concomitantly infiltrate into the bowel, complicating of major complications (including bowel perfor-
removal. Resection of the isolated uterosacral ligament ation, anastomotic leak, and development of
nodule involves separating the bowel from the lesion, obstruction).
isolating the uterine artery and ureter, and then excising
the full nodule. When lesions are bilateral, close atten- Support for shaving of rectal endometriosis is
tion should be paid to resecting only the nodular com- demonstrated by a review of 500 cases published by
ponent, avoiding collateral damage to parasympathetic Donnez et al. It was reported that the resection of
nerves from the inferior gluteal plexus. These nerve a majority of DIE can significantly reduce pain symp-
fibers run toward the bladder in this location, and toms, even without complete resection. Only 8% of
damage to these nerves can result in temporary or women reported recurrence and 84% of women were
permanent difficulty in emptying the bladder. able to conceive following the shaving procedure.
Compared to rectal resection complications including
Bowel Endometriosis laparoconversion, repeat surgery, sepsis, and rectova-
ginal fistulas were all found to be lower [11]. Given the
Treatment of bowel endometriosis elicits contentious increasing number of studies supporting improve-
arguments among endometriosis experts. This is due ment in quality of life with fewer complications,

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Mark Dassel and Alyssa Herrmann

consideration of less aggressive shaving techniques Endometriosis near the ureter is relatively com-
should be considered when appropriate. mon. Surgeons commonly separate disease from this
structure; however, true infiltration of the ureter is
Appendiceal Endometriosis rare, in less than 1% of all DIE [25]. Pain symptom-
atology is often noncyclic and may result in obstruct-
Appendiceal endometriosis is a relatively common ive sequelae including costovertebral angle tenderness,
finding when other forms of DIE are present. The hydronephrosis, and even kidney failure. Like bladder
disease most frequently involves the terminal extent and colorectal endometriosis, medical management of
of the organ and its removal is very effective in redu- ureteral DIE tends to be beneficial in the short term
cing right lower quadrant pain. Because of the relatively but surgery is often required for definitive treatment.
high association between appendiceal involvement and Resection of endometriosis, abutting the ureter can
stage 3 and 4 endometriosis some authors recommend often resolve obstruction, but the surgeon should be
removal of the appendix in these circumstances even prepared to fully resect a portion of the ureter when
when the appendix appears grossly normal [23]. hydronephrosis is present. Ureteroscopic biopsy can
be useful in diagnosis of DIE invading into the ureteral
Urinary Bladder Endometriosis parenchyma when imaging is not definitive. Ureteral
stents may be placed for treatment or presurgically to
Making up 4%–20% of DIE, lesions affecting the urin- aid in surgical ureteral identification.
ary bladder are difficult to detect on imaging (Figure
8.4). Urinary bladder DIE often presents as urinary Diaphragmatic Endometriosis
frequency, urgency, dysuria, and hematuria [24].
These symptoms can be confused with interstitial cyst- Determining the best treatment strategy for diaphrag-
itis/bladder pain syndrome, recurrent urinary tract matic endometriosis can be challenging because it is not
infections, or other bladder conditions, delaying diag- always obvious when a lesion is superficial or deeply
nosis for many years. Cystoscopy can be helpful in infiltrating. This uncertainty results in greater risk
diagnosis even when imaging techniques miss these because the distance from the abdominal peritoneum
lesions. Medical treatments have been largely ineffective through the thin muscular diaphragm and into the
in treatment of this pathology; however, surgical inter- pleura of the thoracic cavity is small. Incidental infil-
vention involving full resection of the lesion has been tration into this space can expose the patient to pul-
quite successful. Complication rates are low, and long- monary complications including pneumothorax lung
term pain relief and improvement of urinary function collapse and infection. As a result, many surgeons
are often excellent [24]. Part of the success of treatment employ conservative fulguration techniques, but these
can be attributed to the frequency at which DIE solely interventions can be insufficient to resolve lesions.
affects the dome of the bladder. DIE lesions that inter- Resective treatments should be performed with
fere with the insertion of the ureter and the urinary a practitioner confident in managing pleurotomy.
trigone have the potential to lead to long-term urinary Anesthesia should be prepared to ventilate the patient
frequency and urgency symptoms postsurgically.

Figure 8.4 Bladder endometriosis on
MRI.

e Cambridge Core terms of use, available at
.009

Pelvic Pain Arising from Endometriosis

using a single lung, and preemptive antibiotic dosing Figure 8.6 Resected Cesarean section deep infiltrating
should be considered. If endometriosis is suspected in endometriosis.
the pleural cavity, especially if the patient has increased
pulmonary symptomatology such as menstrual pattern extent of affected structures, so that the correct expertise
cough hemoptysis associated with menstruation, or is present in case of a larger fascial defect.
suggestive imaging findings, a video-assisted thoraco-
scopy (VATS) should be considered. Cesarean scar endometriosis makes up about 0.3%–
Iatrogenic Endometriosis 0.4% of endometriosis cases. It can have a long incuba-
Iatrogenically produced lesions of endometriosis tend tion period with mean time from surgery to symptoms
to involve incisions of the uterine scar following cae- ranging from 30 months to 30 years. Lesions may be
sarean delivery or the abdominal wall. (Though cutaneous, raised, and discolored or deep in the pelvic
abdominal wall endometriosis is almost always from scar and palpable with deep pressure. Drainage of dark
iatrogenic causes, one notable exception is endomet- “chocolate brown” fluid from the scar site has been
riosis of the umbilicus that can be naturally occurring reported (Figure 8.6). Diagnosis is often made on his-
called a Villar’s nodule.) The predominant treatment tory and physical exam; however, ultrasound and MRI
of these lesions is surgical, though shrinkage of the can be useful. Fine-needle aspiration (FNA) can be
lesions may be accomplished with GnRH analogs. considered if there is significant concern for malig-
Excision need occur only in the symptomatic patient. nancy. Medical treatment with GnRH analogs or dana-
zol does not provide absolute symptom relief. Gold
Common associated symptomatology with abdom- standard treatment remains wide excision, as any cells
inal wall endometriosis is noncyclic abdominal pain that left behind will increase the risk of recurrence [26].
occurs with movement and tenderness of the abdominal
wall (Figure 8.5). The pain typically worsens with men- Conclusion
ses and a nodule is often palpable in the subcutaneous
tissue. Imaging commonly shows thick scarring and When treating the patient suffering from endometri-
characteristic appearance of DIE on MRI or CT. osis, a practitioner must have a sound understanding
However, lesions can also appear cystic and contain of the variable nature of the disease. Each subtype and
blood products. Resection of these lesions in conjunc- affected organ system will have a unique set of symp-
tion with physical therapy can help to resolve the painful toms that will vary with each patient. Taking into
sequelae from these lesions. Surgical planning must be consideration the medical and surgical options,
careful and preoperative imaging should ascertain the a patient-specific treatment plan should be developed,
keeping in mind that the ultimate goal should be
Figure 8.5 Abdominal wall endometriosis on MRI.
95
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Mark Dassel and Alyssa Herrmann

symptom management rather than reduction of dis- 9. Kavallaris A, Kö hler C, Kü hne-Heid R, Schneider A.
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endometriosis among women with deep-infiltrating 26. Yildirim D, Tatar C, Doğan O, et al. Post cesarean scar
endometriosis. nt J Gynaecol Obstet. 2017;139 endometriosis. Turk J Obstet Gynecol.
(2):149–54. 2018;15:33–8.

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Chapter Bladder Pain Syndrome

9 Katherine de Souza and Charles Butrick

Editor’s Introduction however, that definition is meant to be used in the
research setting and does not translate well to clinical
Interstitial cystitis/bladder pain syndrome (IC/BPS) practice. In 2009, the Society for Urodynamics and
is one of the evil quadruplets – diseases Female Urology defined BPS with the following
coexisting with endometriosis. Etiology and even criteria:
the way to obtain proper diagnosis is very
debatable among providers. One of the mainstays • An unpleasant sensation (pain, pressure,
of IC/BPS is pain with full bladder, and patients discomfort) perceived to be related to the urinary
with this condition urinate often because they bladder
want to avoid pain and not because they have
urgency. Diagnosis of IC/BPS may be done based • Associated with lower urinary tract symptoms of
on the symptoms but some practitioners would more than 6 weeks duration
use potassium sensitivity test or cystoscopy with
bladder hydrodistension if necessary. Treatment • In the absence of infection or other identifiable
consists of avoiding foods that irritate the cause [1]
bladder and increase the pain. Oral medications
such as pentosan polysulfate sodium do not Ultimately, BPS is a clinical diagnosis based on
seem to be as effective. Patients with IC/BPS also symptoms that cannot be explained by more trad-
very often have pelvic floor muscle spasm that itional problems such as bladder infection, bladder
may be primary to the onset of bladder pain, and cancer, or other pelvic/bladder pathology. This defin-
treatment of this spasm may be the most ition does present BPS as a diagnosis of exclusion in
effective way to treat IC/BPS. Pelvic floor physical part because the etiology of the disorder is still being
therapy and botulinum toxin A injections to explored.
pelvic floor muscles (not bladder) may be very
helpful. Pathophysiology

What Is Bladder Pain Syndrome? Much progress has been made toward better
understanding of the pathophysiology of BPS in
Definition the past two decades. While there are many the-
ories as to the etiology of BPS, it is generally
First described in the 1800s, bladder pain syndrome is thought to be a pain disorder that likely has
a chronic disorder characterized by pelvic pain and many potential triggers that initiate the symp-
voiding symptoms. This condition is known by sev- toms. Even with the heterogeneity of this pain
eral epithets and corresponding acronyms including disorder there are certain characteristics that
interstitial cystitis (IC), painful bladder syndrome tend to be present in the majority of patients
(PBS), bladder pain syndrome (BPS), and hypersensi- who have BPS. As in all patients with chronic
tive bladder syndrome (HBS). For simplification in pain there is generally a centralized pain compo-
this book chapter, we will refer to this syndrome as nent that results in allodynia, and urinary fre-
bladder pain syndrome or BPS. In 1987, the National quency is the hallmark of this central
Institute of Arthritis, Diabetes, Digestive and Kidney sensitization. Most patients also demonstrate evi-
Diseases proposed diagnostic criteria for clinical trials; dence of urothelial dysfunction as well as periph-
eral sensitization with biopsy evidence of
e Cambridge Core terms of use, available at increased neural density and mast cell activation.
.010

Bladder Pain Syndrome

The urothelial dysfunction results in a deficiency typically the same constellation of symptoms. One
of the glycosaminoglycan (GAG) layer of the bladder exception to this is ulcerative BPS, which is likely
surface. Normal bladder epithelium is impermeable to a unique entity requiring specific therapy [5].
irritants and urinary solutes, so the GAG layer defi-
ciency in patients with BPS allows irritating solutes to Ulcerative Bladder Pain Syndrome
penetrate into the bladder tissue, which is thought to
result in localized inflammatory changes and localized Also known as classic interstitial cystitis, Hunner-type
upregulation (inflammatory cytokines, nerve growth IC, ulcerative IC, and BPS European Society for Study
factors, etc.). Several studies have suggested that there of Interstitial Cystitis (ESSIC) type 3C, ulcerative BPS
is an immune component in which upregulation of has emerged as a discrete condition within the disease
mast cell activation causes activation of capsaicin- spectrum of BPS. This condition is defined by the
sensitive nerve fibers that leads to inflammation presence of Hunner’s lesions on cystoscopy and
which in turn damages the GAG layer of the bladder occurs rarely in approximately 4% of cases [6]. This
epithelium. This also leads to neurogenic upregula- disease presentation tends to respond more reliably to
tion [2]. specific therapies versus BPS in general [7]. There has
been the proposal to treat BPS ESSIC type 3C as
Central sensitization plays a role in the develop- a discrete inflammatory disease process within the
ment of BPS, as the prolonged exposure to noxious syndrome of BPS [5]. Patients with BPS ESSIC type
stimuli (i.e., bladder irritants) leads to activation of 3C tend to have more severe pain and lower bladder
N-methyl-D-aspartate (NMDA) receptions in the dor- capacity when they have a larger number of lesions.
sal horn of the spinal cord. NMDA receptor activation Despite increased symptom severity with increased
decreases the inhibition of dorsal horn neurons, lesions, this is not predictive of long-term response
which lowers the threshold for a stimulus to be per- to interventions [8]. There are a number of interven-
ceived as painful. The process of central sensitization tions that benefit patients with Hunner’s lesions such
is key to many chronic pain disorders that are often as fulguration of lesions, steroid injection into lesions,
associated with patients who have IC/BPS. Classic and cyclosporine A [7]. (See the section “How Is
examples include fibromyalgia, vulvodynia, and endo- Bladder Pain Syndrome Treated?)
metriosis (see Chapter 2). These sensory processing
abnormalities are self-perpetuating as nonpainful How Common Is Bladder Pain
stimuli in sensitized patients are increasingly per- Syndrome?
ceived as painful (e.g., 2 ounces of urine in the bladder
feels like 20 ounces) leading to further C-fiber upre- The prevalence of BPS differs widely depending on the
gulation in the periphery as well as glial cell activation manner in which epidemiological studies are conducted.
centrally. Some authors feel the persistence of neuro- Billing data, self-reported diagnosis, patient question-
genic inflammation results in damage of bladder naires, and medical record extractions have all been
muscle fibers and bladder fibrosis [2, 3] that results used in order to quantify the number of people affected
in the contracted small capacity bladder that is seen in by BPS. There is a significant difference in the preva-
patients with long-standing untreated BPS. lence of the syndrome in women versus men; the ratio of
female to male individuals affected by BPS is five to one.
There is no unified theory for the inciting event For this reason, many studies have focused on the
that leads to the development of BPS. There are many prevalence of BPS in women [7].
potential triggers with “insults” that can occur in the
periphery or centrally that can result in the cascade of One of the most referenced studies on BPS preva-
events that ultimately results in the symptoms of BPS. lence is the RAND Interstitial Cystitis Epidemiology
Theories include bacterial infections, autoimmune (RICE) Study. This population-based study showed
disorder, and environmental factors including stress that 2.70%–6.53% of adult women in the United States
and diet, as well as association with other pain dis- meet the criteria for BPS. Approximately 87% of
orders such as fibromyalgia, irritable bowel syn- women had sought medical care of their symptoms,
drome, and panic disorders. There appear to be and many had been evaluated by multiple providers,
significant genetic factors that contribute to the devel- with a mean number of 3.5 physicians consulted
opment of BPS as well as other chronic pain disorders among study participants. However, fewer than 50%
[4]. Regardless of the original trigger, the end result is had been given any diagnosis associated with their

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Katherine de Souza and Charles Butrick

bladder symptoms and only 9.7% of the women who initially present with only one complaint such as
met the criteria for BPS based on the study definition urinary frequency or dysuria and eventually develop
had been assigned a diagnosis of BPS. This study additional features of BPS with urinary symptoms as
highlights the fact that BPS is more prevalent than well as pain. One defining feature of BPS is increased
many clinicians recognize [9]. pain with increasing fluid volume in bladder. In add-
ition to pain pattern, clinicians should evaluate for
What Is the Typical Course and Impact urinary frequency, urinary urgency, nocturia, and
of Bladder Pain Syndrome? sexual dysfunction. Voiding patterns should be
defined. A hallmark of BPS is frequent voiding for
Based on available data, it is typical for BPS to be the purpose of pain relief. This must be differentiated
diagnosed in the fourth decade of life; however, there from frequent voiding due to urge or avoidance of
may be confounding factors of delayed diagnosis as incontinence. Additionally, voiding volume is pertin-
detailed earlier. Many patients present with culture- ent because patients with BPS have pain with bladder
positive urinary tract infections, but their symptoms filling and void at lower bladder volumes (less than
fail to resolve with adequate treatment of infections. 120 mL) in order to relieve pain. Patients with PBS
Patients may present with one symptom and then may describe “flares” of pain that may be associated
eventually develop all of the typical symptoms in BPS. with a number of stressors including diet, seasonal
It is common for patients to have “flares” of their allergies, or sexual activity. Therefore, timing of
symptoms that may last hours to weeks at a time [7]. symptoms can also be helpful in both initial diagnosis
and choice of intervention [7].
The negative impact of BPS on quality of life is
significant. Patients have high rates of poor sleep, Bladder diaries can be helpful in diagnosis of BPS
depression, social functioning difficulties, and sexual and also serve as useful documentation when deciding
dysfunction. The rate of moderate to severe sexual whether or not an intervention for BPS is effective.
dysfunction is much higher in these patients and Bladder diaries should include number of voids in a 24-
serves as a strong predictor of poor quality of life. hour period as well as details regarding urine volume,
The psychosocial impact of BPS is worse than in presence of pain, incidence of nocturia, presence of
women with endometriosis, overactive bladder, and urgency, and episodes of incontinence. A bladder diary
vulvodynia. Effective treatment of BPS is associated for one 24-hour period is adequate [11].
with improved sleep and sexual function and in turn
associated with improved quality of life. When reviewing past medical history, several con-
ditions occur more frequently in patients with bladder
The economic impact of BPS is difficult to ascer- pain syndrome than in the general population.
tain because of its unknown prevalence. The direct Irritable bowel syndrome, fibromyalgia, vulvodynia,
cost of doctor visits, hospitalizations, and therapies is endometriosis, depression, anxiety, and systemic
greater than the mean annual per-person cost of dis- lupus erythematosus are all more common. Patients
ease such as diabetes and hypertension [10]. The more with BPS have a high rate of previous pelvic surgery
abstract costs such as lost economic contribution and although it is unclear whether this is a contributing
productivity are also significant considering that most factor or an intervention for an incorrect diagnosis in
patients are diagnosed while they are working age and the past. A history of sexual abuse is more common in
the condition is chronic. The cost to individuals patients with pelvic pain compared to the general
should be considered as well. Patients with BPS typic- population. These conditions should be identified
ally have two to four times higher annual medical and treated as appropriate [7].
costs than age-matched controls [10]. Those individ-
uals also suffer the economic burden of lost wages [7]. BPS has symptoms that overlap with those of other
urologic conditions and pelvic pain syndromes, and
How Is Bladder Pain Syndrome a thorough history can distinguish it from those condi-
Diagnosed? tions. While patients with overactive bladder (OAB) will
have symptoms of urinary frequency, patients will typ-
History ically report that this symptom is associated with the fear
of leakage of urine. Patients with BPS have frequency
Obtaining a detailed patient history is the first step in because of discomfort that is typically relieved by void-
diagnosing bladder pain syndrome. Patients may ing. There is an overlap between these two disorders; it is

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Bladder Pain Syndrome

thought that approximately 20% of patients with BPS vaginitis, tenderness, and other potential source of
will be found to have detrusor instability. Therefore, pain or infection. Absence of bladder pain with pal-
these mixed symptoms sometimes require therapy dir- pation should decrease suspicion for BPS.
ected toward both etiologies. Patients with BPS will Examination also identifies other factors that may be
occasionally report leakage of urine yet the leakage that causing a patient’s symptoms such as fibroids, vulvar
is reported is small in amount and often occurs without disease, urethral diverticuli, or pelvic organ prolapse.
the patient experiencing severe urgency or undergoing All of these conditions may potentially lead to high-
stress maneuvers. This atypical loss of urine will often frequency, low-volume voiding. A post-void residual
resolve with correction of the inflammatory changes should be determined at the time of exam to rule out
within the bladder and treatment of the pelvic floor urinary retention as a cause of symptoms [7].
hypertonic dysfunction. BPS can present either as the
patient’s chief complaint and source of pelvic pain or it Diagnostic Testing
can be a component of a complex pain disorder that
might include other pain generators such as endometri- Diagnostic evaluation beyond a thorough history and
osis (patients with endometriosis are four times more physical exam is not required, with the exception of
likely than controls to have BPS) or vulvodynia (50% of urinalysis and urine culture. However, if there are any
patients with BPS have vulvodynia). Patients with low questions regarding the diagnosis, additional testing
voiding frequency and high-volume voids likely have can be helpful.
another etiology for pain [2].
Urinalysis/Urine Culture/Urine Cytology Bladder pain and
Supplemental Questionnaires urgency are characteristic of acute cystitis and there-
fore urinalysis and culture are warranted in patients
Like voiding diaries, questionnaires can be very whose symptoms are suggestive of BPS. Patients with
helpful in both diagnosis and assessment for effect- evidence of urinary tract infection (UTI) should be
iveness in treatments. When initially diagnosing treated and reevaluated for symptoms when the infec-
BPS, questionnaires improve efficiency and accuracy tion has resolved because UTIs are relatively common
of diagnosis. The Pelvic Pain and Urgency/ among patients with BPS. Additionally, urinalysis
Frequency Patient Symptom Scale (PUF)[12] and showing microhematuria may prompt further evalu-
O’Leary-Sant Symptom Screener (OLS)[13] both ation with urine cytology, especially in patients at risk
elicit information about urinary symptoms essential for bladder malignancies (e.g., tobacco users)[7].
to diagnosis of BPS. (See Appendix.) When patients present with new bladder pain symp-
toms that started after a new sexual partner, evalu-
Examination ation of the vaginal canal for the presence of
Mycoplasma or Ureaplasma should be considered.
Pelvic examination of a patient with symptoms sug- Some suggest all patients need to be tested, yet that
gestive of BPS involves a careful assessment of each is not universally accepted [14].
pain generator and the determination of its involve-
ment in the patient’s symptomatology. Patients with Cystoscopy Although cystoscopic evaluation is a
bladder pain syndrome typically will be found to have requirement for the restrictive definition of BPS
tenderness at the bladder base as well as hypertonic intended for research, it is not necessary for clinical
pelvic floor muscles that also are tender and repro- diagnosis. Performing cystoscopy has not been
duce the feeling of pressure or the need to urinate. The found to provide additional diagnostic information
clinician can use this information to determine the beyond that elucidated via history and physical
potential source of the primary pain generator. Many exam. Multiple authors have demonstrated both
patients have both a pelvic floor muscle contribution false negatives and false positives when presence
as well as bladder tenderness. Many patients will also of glomerulations is used to rule in or rule out
report urethral burning yet with pain mapping the BPS. While cystoscopy alone can be misleading, it
“urethral“ burning is often elicited by light touch is essential in identifying those patients with ulcera-
above the urethral meatus – this is a classic finding tive disease. Cystoscopy also allows the clinician to
of BPS. Pain mapping is an essential component of the rule out other etiologies for the persistent bladder
physical exam. Patients should be evaluated for symptoms [6].

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Katherine de Souza and Charles Butrick

Urodynamics Like for cystoscopy, the utility of urodynam- reserved for patients who are not responsive to
ics in BPS is ruling out other etiologies such as bladder conservative therapy with an exception for
outlet obstruction and detrusor overactivity. Therefore, patients who are discovered to have Hunner’s
if there is a question regarding the presence of these lesions.
other conditions, urodynamic testing should be per- • If there is no improvement of symptoms in
formed. Although patients with BPS have been found a clinically meaningful timeframe, diagnosis
to have common findings such as early first sensation to should be reevaulated.
void and decreased bladder capacity, these characteris-
tics are not necessary for diagnosis [15]. Evaluation of Recommendations for treatment of BPS are based
urethral pressures during urodynamics will often dem- on the American Urologic Association (AUA) guide-
onstrate urethral pressures that are elevated (greater lines for the diagnosis and treatment of BPS. The
than 130 cm H2O) in patients who have pelvic floor hierarchy of the treatment recommendations is
hypertonicity. Voiding dysfunction due to the inability based on potential benefit, risk–benefit profile, and
to completely relax the pelvic floor muscles is common severity and reversibility of adverse effects. Treatment
in patients with hypertonicity and BPS [16]. is challenging because there is no one treatment that is
reliably effective for the majority of patients.
Bladder Anesthetic Challenge Test When the clinician Therefore, a trial of multiple treatment approaches
suspects the bladder to be a source of pain, including multimodal therapy may be required before
a relatively simple anesthetic challenge will often an effective regimen is identified for an individual
demonstrate for both the patient and the clinician patient.
that at least temporary relief of pain can be achieved.
The placement of 20 mL of 2% lidocaine combined First-Line Interventions
with 20,000 units of heparin can result in at least 2
hours of marked improvement in pain when pain is All patients should be offered these interventions
originating from the bladder. This diagnostic test has when diagnosed with BPS [7].
replaced the use of potassium chloride in many prac-
tices as a test of bladder hypersensitivity and pain [17]. Patient Education (Clinical Principle)

How Is Bladder Pain Syndrome This element of treatment is important in setting
Treated? patient expectations for their disease course and
options for therapy. Patients should be counseled on
The management of BPS should be guided by the normal bladder function and BPS including the fact
following principles: that there is much still unknown about this condition.
Patients should be educated about the various triggers
• The initial treatment level should be tailored to the to their symptoms and why treatment is typically
individual patient based on severity of symptoms, multimodal. The concept of multiple pain generators
patient preference, and clinician judgment. and the need to treat each one is stressed so that the
patient understands the reasoning behind each of the
• The clinician should target each pain generator treatment modalities and gets her involved in her
and thus therapy will be individualized. Most treatment decisions. Additionally, it is important for
patients will have both bladder and pelvic floor patients to understand that BPS is a chronic condition
pain. Therapy should address both. that may have periodic flares interspersed with
asymptomatic periods.
• If in the best interest of the patient, multiple
treatments may be started simultaneously. General Relaxation/Stress Management (Clinical

• Ineffective treatments should be stopped. Principle)
• Pain management should be a central
It is well established that stress is associated with
consideration throughout treatment, as the heightened pain sensitivity. Therefore, development
ultimate goal of intervention is to minimize pain of relaxation exercises and coping mechanisms can
and therapy side effects while maximizing patient provide relief from symptoms of BPS. As this type of
function. intervention is beyond the scope of practice for most
• Treatment should be implemented from most to gynecologists, a multidisciplinary approach is recom-
least conservative. Surgical intervention should be mended with coordination of care with counselors.

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Bladder Pain Syndrome

Self-Care/Behavior Modification (Clinical Principle) improve symptoms of BPS in more than 60% of
Behavior modification typically includes appropriate patients in multiple studies [7]. Medication side
fluid management (48–64 ounces per day). Dietary effects such as sedation and nausea have been
manipulation is beneficial in approximately two observed in up to 79% of patients. These adverse
thirds of patients. Patient education concerning effects were a major reason for discontinuation of
avoidance of bladder irritants such as acidic foods, the medication, so starting patients at a low dose
alcoholic beverages, and caffeine should be reviewed. such as 10 mg daily and up-titrating to 75–100 mg
The use of over-the-counter supplements is poorly daily over time is recommended.
studied but calcium glyceryl phosphate seems to
benefit many patients with BPS. This appears to Cimetidine (Grade B Evidence) Cimetidine is a histamine
work by neutralizing the acid in certain foods and H2 antagonist. Several studies including a random-
beverages. ized controlled trial (RCT) have shown that this
medication can improve BPS symptoms, although
Second-Line Interventions no long-term follow-up data are available [7].
However, there were no adverse effects reported in
Appropriate Manual Physical Therapy Techniques (Grade trials investigating cimetidine as a potential treat-
A Evidence) ment for BPS, so it has the potential to be a low-
riskintervention. Dosing of this medication varies in
More than 80% of patients with PBS have studies from 200 mg three times daily to 300–400 mg
a component of hypertonic pelvic floor muscle dys- twice daily.
function [7]. This hypertonicity results both in void-
ing dysfunction as well as myofascial pain. The Hydroxyzine (Grade C Evidence) Hydroxyzine is a histamine
constant pressure caused by the muscles results in H1 antagonist that has been shown to improve symp-
the constant feeling of needing to urinate, which toms in some patients [7]. However, the only study
then makes the patient “hold urine” and therefore that demonstrated statistically significant symptom
tends to perpetuate the hypertonicity and pain. relief included only patients with systemic allergies.
This hypertonic dysfunction is easily identified on The existence of systemic allergies may be considered
pelvic examination as well as during the perform- when selecting patients for this medication. A large
ance of urodynamics. If pelvic floor hypertonicity number of patients reported side effects including
and pain are thought to be components then refer- short-term drowsiness and weakness. These adverse
ral to physical therapy for further evaluation and effects were considered serious by patients and were
management of this symptomatology is required. similar to side effects described by patients receiving
It is important to note that strengthening (e.g., placebo medications. In studies, patients were started
through Kegel exercises) is not the goal of pelvic on a lower dose and titrated up with regimens such as
floor physical therapy. These patients need to learn 10 mg daily increased to 50 mg over weeks and 25 mg
to relax their pelvic floor muscles and the exercise daily increased to 75 mg daily over weeks.
techniques are sometimes referred to as “reverse
Kegels.” Multiple studies have shown the benefit in Pentosanpolysulfate (PPS; Grade B Evidence) PPS is a urinary
symptom resolution through the use of manual analgesic that has been widely studied for the treatment
therapy, sometimes referred to as myofascial of BPS including multiple RCTs [7]. Results of these
release. Identification of a qualified pelvic floor studies are conflicting, but aggregations of data from all
physical therapist is important, as these providers RCTs evaluating efficacy of PPS does show that the
are not available in every community. The avail- medication significantly improves symptoms of BPS.
ability of this type of physical therapy in your Of note, there is some evidence to support that PPS is
community can be determined by a visiting www less useful in patients with ulcerative BPS. Dosing of
.womenshealthapta.org or www.pelvicpain.org. this medication is 100 mg three times daily.

Oral Medications Intravesical

Amitriptyline (Grade B Evidence) Amitriptyline is Dimethyl Sulfoxide (DMSO; Grade C Evidence) DMSO is
a tricyclic antidepressant that has been shown to a urinary tract analgesic that has resulted in
improvement in BPS symptoms in multiple studies
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103

Katherine de Souza and Charles Butrick

[7]. The medication is instilled in the patient’s Pain Management
bladder and retained for 15–20 minutes. Longer
intravesical retention of the medication is not As evidenced by the recommendations for treatment
recommended because it is associated with severe in this section, there is a large range of both pharma-
pain due to the medication’s rapid absorption into cological and surgical interventions for BPS [7].
bladder tissue. There are several regimens for these Because of the severe impact of pain on patients’
bladder instillations, although the principle is for quality of life, improvement in pain is a central aim
treatments every 2 weeks for 4–8 weeks with assess- when treating this disorder. While providers should
ment for response to therapy. Additional instilla- use treatment algorithms and work with patients to
tions can be performed as needed with the idea that find appropriate therapy, additional pain control with
there will be progressively longer intervals of pain systemic analgesics may be considered in order to
relief. There are no known significant adverse improve functionality. Again, a multidisciplinary
effects for this treatment. approach may be advantageous. Referral to anesthesia
or pain specialists for management of analgesics such
Heparin (Grade C Evidence) Heparin is an anticoagulant as narcotic pain medication can be very helpful for
that has been shown to improve symptoms of BPS providers who do not have experience with these
both when used alone and when combined with medications in chronic pain patients. Regardless of
other agents. There are several regimens that have whether the primary provider for PBS decides to
been shown to improve symptoms including provide systemic analgesics or refer to another pro-
10,000 IU heparin in 10 mL of sterile water three vider, pain management should adhere to the follow-
times a week for 3 months with retention of ing principles:
1 hour and 25,000 IU in 5 mL of distilled water
twice a week for 3 months. There are no known • Oral analgesics should be used in conjunction with
serious adverse effects; however, the risk–benefit other medications that address BPS with the aim
profile of this intervention has not been fully of minimizing the reliance on narcotics for pain
evaluated, as there are no placebo-controlled trials control. In addition to medication, psychological
available. therapy should be integrated to reduce the
requirement for narcotic pain medications.
Lidocaine (Evidence Grade B) Lidocaine is a topical anes-
thetic that has been most extensively investigated • Narcotics and other medications with high
in combination with other agents for relief of BPS potential abuse should only be prescribed by one
symptoms. Lidocaine can be administered with or provider/clinic. Pain management agreements
without alkalinization. In theory, alkalinization between patients and providers should set
should improve efficacy of treatment because it guidelines for use of these medications and how
improves the penetration of lidocaine into the they are prescribed including responsibilities that
urothelium; however, this is controversial. One of patients must fulfill in order to continue
the advantages to anesthetic-based intravesical medications.
therapy is the use of this approach not only as
a “rescue” intervention but also as one that can be • If narcotics are being used, long-acting agents are
used by the patient for maintenance therapy in preferred over short-acting narcotics except for
more severe cases or when a patient cannot easily breakthrough pain.
reach the clinician involved in the management of
her BPS. Medications should be trialed in a systematic
manner with addition and titration of one medication
Most clinicians use intravesical therapy that at a time so that efficacy of individual treatments for
involves a combination of ingredients that potentially patients can be correctly identified. Medications
provide more benefit than intravesical installations should be initiated at the lowest possible dose and
that involve only one ingredient [18]. The efficacy of increased in a stepwise manner as is appropriate
combination intravesical therapy (often referred to as based on symptoms, pain scores and patient tolerance
“bladder cocktails”) has been reported by many of medication adverse effects. This requires clinicians
authors. (See Appendix: Rescue / therapeutic cocktails to be in close contact with patients.
for bladder pain syndrome flare.)
Although pain relief is an important component of
e Cambridge Core terms of use, available at BPS management, it is important for underlying blad-
.010 der dysfunction to be addressed concurrently in order
to improve function and decrease the need for pain

Bladder Pain Syndrome

medication. Patients should be counseled that fulguration of lesions have shown high response
adequate pain relief is the goal of pain management rates, with 80%–100% of patients experiencing
as complete pain relief is not always possible. improvement in both pain and bladder function.
The treatment effect lasted for up to 23 months in
Third-Line Interventions these studies. One serious adverse effect unique to
laser fulguration is possible delayed bowel perforation
Cystoscopy with Hydrodistention (Evidence Grade C) due to scatter of laser to the bowel. Regardless of
method of fulguration, patients should be counseled
If more conservative therapies have failed, cystoscopy that they may require repeat treatment, approxi-
with hydrodistention under anesthesia can be con- mately 46% in laser studies.
sidered if one has not been done in the recent past
[7]. This procedure allows for visual inspection of the Treatment of Hunner’s lesions with intralesional
bladder epithelium for any abnormalities including steroid injections is advocated by some clinicians.
Hunner’s lesions and to rule out the possibility of Submucosal injection of triamcinolone using either
other pathology that might explain the persistent 10 mg/mL concentration or 40 mg/mL concentration
symptoms. Management of Hunner’s lesions is dis- with a maximum total injection of 60 mg triamcino-
cussed in the text that follows. The bladder capacity lone is recommended. Larger doses of triamcinolone
determined at the time of cystoscopy with hydrodis- have been studied but are not recommended because
tention is also thought to be a prognostic indication of of a lack of high-quality safety information. This
patients who are at risk for poor response to trad- intervention has yielded symptom relief from 7 to 12
itional therapies. Volume under anesthesia of less months in studies.
than 300 mL is a sign of severe disease.
Fourth-Line Interventions
Hydrodistension can be a helpful diagnostic tool
as well as a therapeutic intervention. Its use solely as Neuromodulation (Grade C Evidence)
a diagnostic tool for cannot be recommended [7].
Ideal hydrodistension has yet to be determined but Use of permanent sacral or pudendal neurostimula-
most authors advocate low-pressure, from 60 to 80 cm tion devices is not FDA-approved for BPS; however,
H2O with a duration of less than 10 minutes, although sacral neurostimulator devices are approved for man-
longer duration low-pressure hydrodistension has agement of urinary frequency [7]. Regarding sacral
been used by some providers. The duration of symp- versus pudendal nerve stimulation, a single random-
tom relief is variable across multiple studies. The ized crossover trial did show patient preference
major adverse effects experienced by patients in toward pudendal nerve stimulation. Overall, there is
these studies were temporary flare of symptoms and a relatively high response rate to implants, from 66%
rare episodes of bladder rupture. Providers and to 94%. Patients with BPS appeared to have a higher
patients must determine if the benefit of hydrodisten- incidence of implant site pain requiring revision of
sion is worth the risk of a short-term increase in pulse generator site or even removal. In recent studies,
symptoms. removal of devices occurred in up to 28% of patients
due to low efficacy of treatment or intolerable side
Treatment of Hunner’s Lesions (Grade C Evidence) effects. There are multiple cohort studies in the litera-
If identified, Hunner’s lesions can managed at the ture, while not typically randomized and often with
time of cystoscopy via either fulgration or steroid follow-up of 1 year, showing symptom improvement
injection [7]. Fulguration can be achieved via laser including urinary frequency, pelvic pain, and voiding
or electrocautery and this intervention has shown dysfunction [19].
significant improvement in pain, including complete
resolution of pain, in more than 75% of patients. Fifth-Line Interventions
Patients also experienced relief from urinary fre-
quency. The duration of effectiveness for fulguration Intradetrusor Botulinum Toxin A (Grade C Evidence)
of Hunner’s lesions is not clearly defined. Adverse
effects from this intervention are rare but do include Botulinum toxin A (BTX-A) can be used either alone
the rare risk of bladder perforation and need for or in conjunction with hydrodistension [7]. There is
subsequent repair. Similarly, studies on laser not strong evidence to support recommendation for

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Katherine de Souza and Charles Butrick

or against contaminant treatment with bladder hydro- Sixth-Line Interventions
distension. Studies have shown up to 86% efficacy for
BTX-A; however, almost all patient experienced return Major Surgery (Evidence Grade C)
to baseline pain and function after a certain time inter-
val, commonly 3 months. There is a range of intervals Surgical management of BPS should be reserved for
between repeat treatments as well as a range of locations patients with severe disease that has been unrespon-
for injection including the trigone alone, the bladder sive to other treatments [7]. Surgical interventions are
walls alone, and a combination of both. No definitive irreversible and lead to significant changes in lifestyle
recommendation for site of bladder injection of BTX-A that patients may not wish to undertake considering
exists. The recommended dose is 100 U BTX-A, as there that they may not experience symptoms relief follow-
are significant potential adverse effects that increase with ing surgery even if the bladder is completely removed.
higher doses. Adverse effects include dysuria as well as The likelihood of favorable outcomes can be increased
urinary retention. Retention can range from mild, by carefully selecting the patients to whom these pro-
requiring abdominal straining in order to void, to severe cedures are offered. Patients who have small bladder
with the need intermittent self-catheterization. These capacity under anesthesia and failed to improve with
effects generally resolved in 1 to 3 months, but in some more conservative measures are most likely to benefit
cases, they persisted. Patients should be thoroughly from surgery. Additionally, patients with little or no
counseled and accept the risk of severe urinary retention neuropathic pain are more likely to experience symp-
requiring self-catherization prior to use of BTX-A. tom relief from surgery.
Additionally, patients with known urinary retention
may not be good candidates for this therapy given the Diversion with or without Cystectomy This procedure
adverse effect profile. involves diversion of urine to an alternative to the
bladder such as an ileal conduit. Because of the
Cyclosporin A (Grade C Evidence) possibility of persistent pain following removal of
the bladder, cystectomy may or not be performed at
Cyclosporine A (CyA) is an immunosuppressive the time of diversion. Creation of a diversion has the
agent that has been shown to be particularly effective potential to effectively improve urinary frequency, so
for patients with ulcerative BPS [7]. The recom- patients for whom this is a major complaint may be
mended dose is 2–3 mg/kg/day in two divided good candidates if they have failed conservative
doses with a maximum dose of 300 mg daily. If measures.
symptom control is established yet side effects such
as an increase in blood pressure or creatinine occur, Substitution Cystoplasty : This procedure involves excis-
some patients will require a reduction in dose. ing a portion of the bladder thought to be contribut-
A dose reduction to as little as 1 mg/kg/day should ing to BPS. In some cases, the trigone is excised while
be considered. Clinicians should carefully follow the in other cases it is preserved. The benefit of trigone
concerning side effects, which include hypertension excision is that the area is thought to be a source of
and deterioration of renal function. In a trial com- pain and is a common location for Hunner’s lesions;
paring CyA to pentosanpolysulfate, 75% of patients however, trigone excision increases the risk of urinary
experienced improvement of symptoms in 6 months retention, requiring chronic self-catheterization.
with CyA. Other studies have shown that this medi- Patients with Hunner’s lesions and small bladder cap-
cation is effective in as little as 6 weeks, with 87% of acity under anesthesia are more likely to benefit from
patients reporting markedly improved urinary func- substitution cystoplasty. Patients who identify the
tion and resolution of pain. While adverse effects are urethra as their main site of discomfort are less likely
quite common, present in 94% of patients in one to benefit.
study, most are minor. Serious adverse effects
include hypertension, renal impairment, and cuta- Treatments That Should Not Be Offered
neous lymphoma. Therefore, the use of this medica-
tion should be done with carefully performed Although there is no reliable intervention that will
informed consent as well as a program of close fol- improve the BPS for every patient, several therapies
low-up especially as it relates to blood pressure and have shown no benefit and should not be offered to
renal function changes. patients because the risk of the intervention out-
weighs potential benefits.

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Bladder Pain Syndrome

• Long-Term Antibiotics (Grade B Evidence) symptoms although there was significant placebo
Antibiotics should be reserved for patients with effect as well. Activation of SH2-containing inositol-
positive urine cultures. There has not been any 5΄-phosphatase 1, P2X3 receptor antagonists, and α1
benefit to antibiotic therapy for bladder pain of adrenoceptor antagonists is also under investigation
noninfectious etiology. Given the serious potential and has shown success in improving symptoms of
adverse outcome of antibiotic resistance, this BPS. These potential treatments may have a systemic
therapy should not be offered [7]. effect addressing neurogenic inflammation. There are
also trials of bladder treatments such as intravesical
• Intravesical Bacillus Calmette-Guérin (BCG; liposomes and toll-like receptor antagonists. These
Grade B Evidence) There have been several two areas of study would affect only the symptoms
studies that demonstrated no significant of BPS that arise from the bladder itself and not
difference between BCG instillation and placebo. address symptoms due to central sensitization [5].
Because there is no evidence of benefit and there
have been serious adverse effects such as sepsis Summary
and death associated with BCG, this therapy
should not be offered [7]. Bladder pain syndrome affects approximately 5% of
all women. As our understanding of this pain disorder
• High-Pressure Long-Duration Hydrodistension advances we now realize that patients can present with
(Grade C Evidence) There has been no reliable many clinical phenotypes. Some will present with
benefit to performing hydrodistension at isolated bladder symptoms but some will present
pressures greater than 80 to 100 mm H2 with a history of various types of chronic pain dis-
O. Similarly, longer durations of hours or repeated orders with multiple pain generators. Given our
30-minute intervals have shown no reliable understanding of centralized pain, the management
benefit. However, these interventions place of this visceral pain syndrome requires that the clin-
patients at greater risk for complications such as ician identify each pain generator, and using
sepsis and bladder rupture. Therefore, this a multimodal approach, attempt to downregulate
technique of hydrodistension is recommended each component of the pain using the therapeutic
against [7]. options that we have discussed. Most patients will
benefit from this approach, especially if identification
• Long-Term Systemic Glucocorticoid of BPS and initiation of therapy are undertaken in
Administration (Grade C Evidence) Although a timely fashion. As with any pain disorder, the longer
studies have shown that this intervention can the delay in the diagnosis and initiation of therapy the
provide symptoms relief, long-term steroid use is more difficult it will be to manage.
associated with diabetes, hypertension, and
immunocompromise. For this reason, this Five Things You Need to Know
treatment is not recommended [7].
• Hallmarks of bladder pain syndrome (BPS) are
Experimental/Future bladder pain and urgency in the setting of
frequent small-volume voids for the purpose of
Many current studies are focusing on whether it is pain relief.
beneficial to “phenotype” individuals with BPS in
order to more effectively guide treatment regimens. • This condition causes severely diminished quality of
There are several investigatory treatments that are life but is frequently underdiagnosed by clinicians
targeting immune modulation that contribute to despite simple clinical criteria for diagnosis.
bladder inflammation. Nerve growth factor (NGF) is
more common in animal models, and anti-NGF with • Although all patients should be offered education,
monoclonal antibodies is one of the treatments cur- stress management, and behavioral modification
rently under investigation. Although studies in as first-line treatment, no single reliable
humans have not shown significant improvement, pharmaceutical or surgical intervention will work
larger population studies may reveal this to be an for all patients. Treatments should be
effective treatment. Likewise, antitumor necrosis fac- individualized based on assessment of active pain
tor-α (TNF-α) is under investigation using adalimu- generators. Most patients with BPS have both
mab to block the cytokine’s proinflammatory effect. bladder and pelvic floor myofascial components
Treatment revealed significant improvement in to their pain.

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Katherine de Souza and Charles Butrick

• The goal of therapy is to identify triggers to 9. Berry SH, Elliott MN, Suttorp M, et al. Prevalence of
their pain disorder and to treat each pain symptoms of bladder pain syndrome/interstitial
generator. Most patients will have marked cystitis among adult females in the United States.
improvement in symptomatology but J Urol. 2011;186(2):540–4. DOI: 10.1016/j
intermittent flares are common even after .juro.2011.03.132
appropriate therapy.
10. Clemens JQ, Meenan RT, Keeffe MCO, Kimes T,
• While ulcerative IC is relatively rare, Calhoun EA. Costs of interstitial cystitis in a managed
approximately 4%, it represents a unique form care population. Urology. 2008;71(5):776–81. DOI:
and typically is associated with persistent 10.1016/j.urology.2007.11.154.COSTS
symptoms despite appropriate therapy.
Cystoscopy is required to identify and treat 11. Mazurick CA, Landis JR. Evaluation of repeat daily
active Hunner’s lesions. voiding measures in the national interstitial cystitis
data base study. J Urol. 2000;163(4):1208–11. DOI:
References 10.1016/S0022-5347(05)67725-7

1. Hanno P, Dmochowski R. Status of International 12. Powell CR, Kreder KJ. Long-term outcomes of
Consensus on Interstitial Cystitis/Bladder Pain urgency-frequency syndrome due to painful bladder
Syndrome/Painful Bladder Syndrome: 2008 snapshot. syndrome treated with sacral neuromodulation and
Neurourol Urodyn. 2009;28(5):274–86. DOI: 10.1002/ analysis of failures. J Urol. 2010;183(1):173–6. DOI:
nau 10.1016/j.juro.2009.08.142

2. Bharucha AE, Lee TH. Anorectal and pelvic pain. 13. O’Leary MP, Sant GR, Fowler FJ, Whitmore KE,
Mayo Clin Proc. 2016;91(10):1471–85. DOI: 10.1037/ Spolarich-Kroll J. The interstitial cystitis symptom
a0038432.Latino index and problem index. Urology. 1997;49(5
Suppl.):58–63. DOI: 10.1016/S0090-4295(99)
3. Butrick CW. Interstitial cystitis/bladder pain 80333-1
syndrome. Management of the pain disorder:
a urogynecology perspective. Urol Clin North 14. Combaz-Söhnchen N, Kuhn A. A systematic
Am. 2012;39(3):377–87. DOI: 10.1016/j review of Mycoplasma and Ureaplasma in
.ucl.2012.06.007 urogynaecology. Geburtshilfe Frauenheilkd. 2017;77
(12):1299–1303.
4. Jhang J, Kuo H. Pathomechanism of interstitial
cystitis/bladder pain syndrome and mapping the 15. Kuo Y-C, Kuo H-C. The urodynamic
heterogeneity of disease. Int Neurourol J. 2016;20 characteristics and prognostic factors of patients with
(Suppl 2):S95–S104. interstitial cystitis/bladder pain syndrome.
Int J Clin Pract. 2013;67(9):863–9. DOI: 10.1111/
5. Andersson KE, Birder L. Current pharmacologic ijcp.12116
approaches in painful bladder research: an update.
Int Neurourol J. 2017;21(4):235–42. DOI: 10.5213/ 16. Butrick C, Sanford D, Hou Q, Mahnken J. Chronic
inj.1735022.511 pelvic pain syndromes: clinical, urodynamic,
and urothelial observations. Int Urogynecol
6. Ottem DP, Teichman JMH. What is the value of J Pelvic Floor Dysfunct. 2009;20(9):
cystoscopy with hydrodistension for interstitial 1047–53.
cystitis? Urology. 2005;66(3):494–9. DOI: 10.1016/j
.urology.2005.04.011 17. Evans RJ, Sant GR. Current diagnosis of interstitial
cystitis: an evolving paradigm. Urology. 2007;69
7. Hanno PM, Burks DA, Clemens JQ, et al. (Suppl. 4A):64–72. DOI: 10.1016/j
American Urological Association (AUA) guideline: .urology.2006.05.048
diagnosis and treatment of interstitial cystitis/
bladder pain syndrome. J Urol. 2011;185 18. Cvach K, Rosamilia A. Review of intravesical
(6):2162–70. therapies for bladder pain syndrome/
interstitial cystitis. Transl Androl Urol. 2015;4
8. Akiyama Y, Niimi A, Nomiya A, et al. Extent (6):629–37. DOI: 10.3978/j.issn.2223-4683
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symptom severity and clinical parameters
in Hunner type interstitial cystitis patients. 19. Laviana A, Jellison F, Kim JH. Sacral
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10.1002/nau.23467 overactive bladder, interstitial cystitis, and
painful bladder syndrome. Neurosurg Clin North
Am. 2014;25(1):33–46. DOI: 10.1016/j
.nec.2013.08.001

e Cambridge Core terms of use, available at
.010

Bladder Pain Syndrome

Appendix

To help your physician determine if you have interstitial cystitis, please put a check mark to the
most appropriate response to each of the questions below. then add up the numbers to the left of the
check marks and write the total below.

Symptom index Problem index

During the past month: During the past month, how much has each
following been a problem for you?
Q1. How often have you felt the strong need
to urinate with little or no warning? Q1. Frequent urination during the day?
0. Not at all. 0. No problem.
1. Less than 1 time in 5. 1. Very small problem.
2. Less than half the time. 2. Small problem.
3. About half the time. 3. Medium problem.
4. More than half the time. 4. Big problem.
5. Almost always.
Q2. Getting up at night to urinate?
Q2. Have you had to urinate less than two hours 0. No problem.
after you finished urinating? 1. Very small problem.
2. Small problem.
0. Not at all. 3. Medium problem.
1. Less than 1 time in 5. 4. Big problem.
2. Less than half the time.
3. About half the time. Q3. Need to urinate with little warning?
4. More than half the time.
5. Almost always. 0. No problem.
1. Very small problem.
Q3. How often did you most typically get up 2. Small problem.
at night to urinate? 3. Medium problem.
0. None. 4. Big problem.
1. Once.
2. Two times. Q4. Burning, pain, discomfort, or pressure in your
3. Three times. bladder?
4. Four times. 0. No problem.
5. Five or more times. 1. Very small problem.
2. Small problem.
Q4. Have you experienced pain or burning 3. Medium problem.
in your bladder? 4. Big problem.

0. Not at all. Add the numeric values of the checked entries:
1. A few times. total score:
2. Almost always.
3. Fairly often.
4. Usually.

Add the numeric values of the checked entries:
total score:

Figure 9.1 O’Leary-Sant symptom screener.

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Katherine de Souza and Charles Butrick

PELVIC PAIN and URGENCY/FREQUENCY
PATIENT SYMPTOM SCALE

Patient’s Name: Today’s Date:

Please circle the answer that best describes how you feel for each question,

01 2 34 SYMPTOM BOTHER
11-14 15-19 20+ SCORE SCORE

1 How many times do you void during the 3-6 7-10 2 3 4+
waking hours? Moderate Severe
15-19
2 a. How many times do you void at 01
night?

b. How many times do you void so

what extent does it usually bother None Mild

you?

3 Are you currently sexually active.

YES NO

4

a. IF YOU ARE SEXUALLY Never Occasionally Usually Always
ACTIVE, do you now or have
you ever had pain or symptoms
during or after sexual intercourse?

b. Has pain or urgency ever made Never Occasionally Usually Always
you avoid sexual intercourse? Never Occasionally Usually Always

5

Do you have pain associated with your
bladder or in your pelvis (vagina, lower
abdomen, urethra, perineum)?

6 Do you still urgency shortly Never Occasionally Usually Always
after urinating? Mild Moderate Severe

7 a. If you have pain, is it usually Never Occasionally Usually Always
Mild Moderate Severe
b. How often does your pain bother
you? Never Occasionally Usually Always

8 a. If you have urgency, is it usually

b. How often does your urgency
bother you?

SYMPTOM SCORE (1, 2a, 4a, 5, 6, 7a, 8a)
BOTHER SCORE (2b, 4b, 7b, 8b)

TOTAL SCORE (Symptom Score + Bother Score) =

Figure 9.2 Pelvic pain and urgency/frequency patient symptom scale.

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Bladder Pain Syndrome

Therapeutic Cocktail for Bladder Pain Syndrome Flare

Supplies: • 3mL syringe
• 18 gauge needle
• Lidocaine 2% – 20mL • #8 French Pediatric feeding tube
• 1mL Triamcinolone 40mg/1mL • 10mL Lidocaine Hydrochloride
• 1mL Heparin Sodium 20,000
Jelly USP, 2%
units/mL
• Catheter Tray
• 30mL syringe

Procedure:
• Draw up 20mL of Lidocaine in 30 mL syringe
• Draw up 120mL of Triamcinolone in 3 mL syringe followed by 1mL of Heparin
• Inject into 30mL syringe
• Explain procedure to patient
• Have patient void before procedure

If symptoms of bladder infection present, dipstick urine to rule out infection
If positive do not proceed, if negative proceed
While patient is in Lithotomy position, open catheter tray and supplies
Cleanse labia and urethra for catheterization
Insert small amount of Lidocaine Jelly to use as lubricant, can use regular
lubricant
Insert Pediatric catheter – check for post void residual
• Then inject Appell Cocktail slowly
• Pull catheter out
• Instruct to try not to void for 2 hours

May reschedule weekly or up to three times week if needed. Average is 6 weeks
of treatment and then as needed

Figure 9.3 Rescue/therapeutic cocktails for bladder pain syndrome flare. When patients have a flare in their bladder symptoms the clinician
should always consider the possibility that they have a bladder infection. Also in the differential is a flare of myofascial pain that often
accompanies BPS. After evaluation, if a component of a flare is thought to be due to bladder pain, a rescue cocktail should be administered. The
patient’s response to this will also clarify for the patient and the clinician if the bladder is a significant pain generator at this time. This can also
be used during the initial evaluation of the patient’s symptoms of pelvic pain, to determine if the bladder is involved.

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Chapter Bladder Pain Syndrome

9 Katherine de Souza and Charles Butrick

Editor’s Introduction however, that definition is meant to be used in the
research setting and does not translate well to clinical
Interstitial cystitis/bladder pain syndrome (IC/BPS) practice. In 2009, the Society for Urodynamics and
is one of the evil quadruplets – diseases Female Urology defined BPS with the following
coexisting with endometriosis. Etiology and even criteria:
the way to obtain proper diagnosis is very
debatable among providers. One of the mainstays • An unpleasant sensation (pain, pressure,
of IC/BPS is pain with full bladder, and patients discomfort) perceived to be related to the urinary
with this condition urinate often because they bladder
want to avoid pain and not because they have
urgency. Diagnosis of IC/BPS may be done based • Associated with lower urinary tract symptoms of
on the symptoms but some practitioners would more than 6 weeks duration
use potassium sensitivity test or cystoscopy with
bladder hydrodistension if necessary. Treatment • In the absence of infection or other identifiable
consists of avoiding foods that irritate the cause [1]
bladder and increase the pain. Oral medications
such as pentosan polysulfate sodium do not Ultimately, BPS is a clinical diagnosis based on
seem to be as effective. Patients with IC/BPS also symptoms that cannot be explained by more trad-
very often have pelvic floor muscle spasm that itional problems such as bladder infection, bladder
may be primary to the onset of bladder pain, and cancer, or other pelvic/bladder pathology. This defin-
treatment of this spasm may be the most ition does present BPS as a diagnosis of exclusion in
effective way to treat IC/BPS. Pelvic floor physical part because the etiology of the disorder is still being
therapy and botulinum toxin A injections to explored.
pelvic floor muscles (not bladder) may be very
helpful. Pathophysiology

What Is Bladder Pain Syndrome? Much progress has been made toward better
understanding of the pathophysiology of BPS in
Definition the past two decades. While there are many the-
ories as to the etiology of BPS, it is generally
First described in the 1800s, bladder pain syndrome is thought to be a pain disorder that likely has
a chronic disorder characterized by pelvic pain and many potential triggers that initiate the symp-
voiding symptoms. This condition is known by sev- toms. Even with the heterogeneity of this pain
eral epithets and corresponding acronyms including disorder there are certain characteristics that
interstitial cystitis (IC), painful bladder syndrome tend to be present in the majority of patients
(PBS), bladder pain syndrome (BPS), and hypersensi- who have BPS. As in all patients with chronic
tive bladder syndrome (HBS). For simplification in pain there is generally a centralized pain compo-
this book chapter, we will refer to this syndrome as nent that results in allodynia, and urinary fre-
bladder pain syndrome or BPS. In 1987, the National quency is the hallmark of this central
Institute of Arthritis, Diabetes, Digestive and Kidney sensitization. Most patients also demonstrate evi-
Diseases proposed diagnostic criteria for clinical trials; dence of urothelial dysfunction as well as periph-
eral sensitization with biopsy evidence of
e Cambridge Core terms of use, available at increased neural density and mast cell activation.

Bladder Pain Syndrome

The urothelial dysfunction results in a deficiency typically the same constellation of symptoms. One
of the glycosaminoglycan (GAG) layer of the bladder exception to this is ulcerative BPS, which is likely
surface. Normal bladder epithelium is impermeable to a unique entity requiring specific therapy [5].
irritants and urinary solutes, so the GAG layer defi-
ciency in patients with BPS allows irritating solutes to Ulcerative Bladder Pain Syndrome
penetrate into the bladder tissue, which is thought to
result in localized inflammatory changes and localized Also known as classic interstitial cystitis, Hunner-type
upregulation (inflammatory cytokines, nerve growth IC, ulcerative IC, and BPS European Society for Study
factors, etc.). Several studies have suggested that there of Interstitial Cystitis (ESSIC) type 3C, ulcerative BPS
is an immune component in which upregulation of has emerged as a discrete condition within the disease
mast cell activation causes activation of capsaicin- spectrum of BPS. This condition is defined by the
sensitive nerve fibers that leads to inflammation presence of Hunner’s lesions on cystoscopy and
which in turn damages the GAG layer of the bladder occurs rarely in approximately 4% of cases [6]. This
epithelium. This also leads to neurogenic upregula- disease presentation tends to respond more reliably to
tion [2]. specific therapies versus BPS in general [7]. There has
been the proposal to treat BPS ESSIC type 3C as
Central sensitization plays a role in the develop- a discrete inflammatory disease process within the
ment of BPS, as the prolonged exposure to noxious syndrome of BPS [5]. Patients with BPS ESSIC type
stimuli (i.e., bladder irritants) leads to activation of 3C tend to have more severe pain and lower bladder
N-methyl-D-aspartate (NMDA) receptions in the dor- capacity when they have a larger number of lesions.
sal horn of the spinal cord. NMDA receptor activation Despite increased symptom severity with increased
decreases the inhibition of dorsal horn neurons, lesions, this is not predictive of long-term response
which lowers the threshold for a stimulus to be per- to interventions [8]. There are a number of interven-
ceived as painful. The process of central sensitization tions that benefit patients with Hunner’s lesions such
is key to many chronic pain disorders that are often as fulguration of lesions, steroid injection into lesions,
associated with patients who have IC/BPS. Classic and cyclosporine A [7]. (See the section “How Is
examples include fibromyalgia, vulvodynia, and endo- Bladder Pain Syndrome Treated?)
metriosis (see Chapter 2). These sensory processing
abnormalities are self-perpetuating as nonpainful How Common Is Bladder Pain
stimuli in sensitized patients are increasingly per- Syndrome?
ceived as painful (e.g., 2 ounces of urine in the bladder
feels like 20 ounces) leading to further C-fiber upre- The prevalence of BPS differs widely depending on the
gulation in the periphery as well as glial cell activation manner in which epidemiological studies are conducted.
centrally. Some authors feel the persistence of neuro- Billing data, self-reported diagnosis, patient question-
genic inflammation results in damage of bladder naires, and medical record extractions have all been
muscle fibers and bladder fibrosis [2, 3] that results used in order to quantify the number of people affected
in the contracted small capacity bladder that is seen in by BPS. There is a significant difference in the preva-
patients with long-standing untreated BPS. lence of the syndrome in women versus men; the ratio of
female to male individuals affected by BPS is five to one.
There is no unified theory for the inciting event For this reason, many studies have focused on the
that leads to the development of BPS. There are many prevalence of BPS in women [7].
potential triggers with “insults” that can occur in the
periphery or centrally that can result in the cascade of One of the most referenced studies on BPS preva-
events that ultimately results in the symptoms of BPS. lence is the RAND Interstitial Cystitis Epidemiology
Theories include bacterial infections, autoimmune (RICE) Study. This population-based study showed
disorder, and environmental factors including stress that 2.70%–6.53% of adult women in the United States
and diet, as well as association with other pain dis- meet the criteria for BPS. Approximately 87% of
orders such as fibromyalgia, irritable bowel syn- women had sought medical care of their symptoms,
drome, and panic disorders. There appear to be and many had been evaluated by multiple providers,
significant genetic factors that contribute to the devel- with a mean number of 3.5 physicians consulted
opment of BPS as well as other chronic pain disorders among study participants. However, fewer than 50%
[4]. Regardless of the original trigger, the end result is had been given any diagnosis associated with their

99at 20:21:51,

Katherine de Souza and Charles Butrick

bladder symptoms and only 9.7% of the women who initially present with only one complaint such as
met the criteria for BPS based on the study definition urinary frequency or dysuria and eventually develop
had been assigned a diagnosis of BPS. This study additional features of BPS with urinary symptoms as
highlights the fact that BPS is more prevalent than well as pain. One defining feature of BPS is increased
many clinicians recognize [9]. pain with increasing fluid volume in bladder. In add-
ition to pain pattern, clinicians should evaluate for
What Is the Typical Course and Impact urinary frequency, urinary urgency, nocturia, and
of Bladder Pain Syndrome? sexual dysfunction. Voiding patterns should be
defined. A hallmark of BPS is frequent voiding for
Based on available data, it is typical for BPS to be the purpose of pain relief. This must be differentiated
diagnosed in the fourth decade of life; however, there from frequent voiding due to urge or avoidance of
may be confounding factors of delayed diagnosis as incontinence. Additionally, voiding volume is pertin-
detailed earlier. Many patients present with culture- ent because patients with BPS have pain with bladder
positive urinary tract infections, but their symptoms filling and void at lower bladder volumes (less than
fail to resolve with adequate treatment of infections. 120 mL) in order to relieve pain. Patients with PBS
Patients may present with one symptom and then may describe “flares” of pain that may be associated
eventually develop all of the typical symptoms in BPS. with a number of stressors including diet, seasonal
It is common for patients to have “flares” of their allergies, or sexual activity. Therefore, timing of
symptoms that may last hours to weeks at a time [7]. symptoms can also be helpful in both initial diagnosis
and choice of intervention [7].
The negative impact of BPS on quality of life is
significant. Patients have high rates of poor sleep, Bladder diaries can be helpful in diagnosis of BPS
depression, social functioning difficulties, and sexual and also serve as useful documentation when deciding
dysfunction. The rate of moderate to severe sexual whether or not an intervention for BPS is effective.
dysfunction is much higher in these patients and Bladder diaries should include number of voids in a 24-
serves as a strong predictor of poor quality of life. hour period as well as details regarding urine volume,
The psychosocial impact of BPS is worse than in presence of pain, incidence of nocturia, presence of
women with endometriosis, overactive bladder, and urgency, and episodes of incontinence. A bladder diary
vulvodynia. Effective treatment of BPS is associated for one 24-hour period is adequate [11].
with improved sleep and sexual function and in turn
associated with improved quality of life. When reviewing past medical history, several con-
ditions occur more frequently in patients with bladder
The economic impact of BPS is difficult to ascer- pain syndrome than in the general population.
tain because of its unknown prevalence. The direct Irritable bowel syndrome, fibromyalgia, vulvodynia,
cost of doctor visits, hospitalizations, and therapies is endometriosis, depression, anxiety, and systemic
greater than the mean annual per-person cost of dis- lupus erythematosus are all more common. Patients
ease such as diabetes and hypertension [10]. The more with BPS have a high rate of previous pelvic surgery
abstract costs such as lost economic contribution and although it is unclear whether this is a contributing
productivity are also significant considering that most factor or an intervention for an incorrect diagnosis in
patients are diagnosed while they are working age and the past. A history of sexual abuse is more common in
the condition is chronic. The cost to individuals patients with pelvic pain compared to the general
should be considered as well. Patients with BPS typic- population. These conditions should be identified
ally have two to four times higher annual medical and treated as appropriate [7].
costs than age-matched controls [10]. Those individ-
uals also suffer the economic burden of lost wages [7]. BPS has symptoms that overlap with those of other
urologic conditions and pelvic pain syndromes, and
How Is Bladder Pain Syndrome a thorough history can distinguish it from those condi-
Diagnosed? tions. While patients with overactive bladder (OAB) will
have symptoms of urinary frequency, patients will typ-
History ically report that this symptom is associated with the fear
of leakage of urine. Patients with BPS have frequency
Obtaining a detailed patient history is the first step in because of discomfort that is typically relieved by void-
diagnosing bladder pain syndrome. Patients may ing. There is an overlap between these two disorders; it is

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Bladder Pain Syndrome

thought that approximately 20% of patients with BPS vaginitis, tenderness, and other potential source of
will be found to have detrusor instability. Therefore, pain or infection. Absence of bladder pain with pal-
these mixed symptoms sometimes require therapy dir- pation should decrease suspicion for BPS.
ected toward both etiologies. Patients with BPS will Examination also identifies other factors that may be
occasionally report leakage of urine yet the leakage that causing a patient’s symptoms such as fibroids, vulvar
is reported is small in amount and often occurs without disease, urethral diverticuli, or pelvic organ prolapse.
the patient experiencing severe urgency or undergoing All of these conditions may potentially lead to high-
stress maneuvers. This atypical loss of urine will often frequency, low-volume voiding. A post-void residual
resolve with correction of the inflammatory changes should be determined at the time of exam to rule out
within the bladder and treatment of the pelvic floor urinary retention as a cause of symptoms [7].
hypertonic dysfunction. BPS can present either as the
patient’s chief complaint and source of pelvic pain or it Diagnostic Testing
can be a component of a complex pain disorder that
might include other pain generators such as endometri- Diagnostic evaluation beyond a thorough history and
osis (patients with endometriosis are four times more physical exam is not required, with the exception of
likely than controls to have BPS) or vulvodynia (50% of urinalysis and urine culture. However, if there are any
patients with BPS have vulvodynia). Patients with low questions regarding the diagnosis, additional testing
voiding frequency and high-volume voids likely have can be helpful.
another etiology for pain [2].
Urinalysis/Urine Culture/Urine Cytology Bladder pain and
Supplemental Questionnaires urgency are characteristic of acute cystitis and there-
fore urinalysis and culture are warranted in patients
Like voiding diaries, questionnaires can be very whose symptoms are suggestive of BPS. Patients with
helpful in both diagnosis and assessment for effect- evidence of urinary tract infection (UTI) should be
iveness in treatments. When initially diagnosing treated and reevaluated for symptoms when the infec-
BPS, questionnaires improve efficiency and accuracy tion has resolved because UTIs are relatively common
of diagnosis. The Pelvic Pain and Urgency/ among patients with BPS. Additionally, urinalysis
Frequency Patient Symptom Scale (PUF)[12] and showing microhematuria may prompt further evalu-
O’Leary-Sant Symptom Screener (OLS)[13] both ation with urine cytology, especially in patients at risk
elicit information about urinary symptoms essential for bladder malignancies (e.g., tobacco users)[7].
to diagnosis of BPS. (See Appendix.) When patients present with new bladder pain symp-
toms that started after a new sexual partner, evalu-
Examination ation of the vaginal canal for the presence of
Mycoplasma or Ureaplasma should be considered.
Pelvic examination of a patient with symptoms sug- Some suggest all patients need to be tested, yet that
gestive of BPS involves a careful assessment of each is not universally accepted [14].
pain generator and the determination of its involve-
ment in the patient’s symptomatology. Patients with Cystoscopy Although cystoscopic evaluation is a
bladder pain syndrome typically will be found to have requirement for the restrictive definition of BPS
tenderness at the bladder base as well as hypertonic intended for research, it is not necessary for clinical
pelvic floor muscles that also are tender and repro- diagnosis. Performing cystoscopy has not been
duce the feeling of pressure or the need to urinate. The found to provide additional diagnostic information
clinician can use this information to determine the beyond that elucidated via history and physical
potential source of the primary pain generator. Many exam. Multiple authors have demonstrated both
patients have both a pelvic floor muscle contribution false negatives and false positives when presence
as well as bladder tenderness. Many patients will also of glomerulations is used to rule in or rule out
report urethral burning yet with pain mapping the BPS. While cystoscopy alone can be misleading, it
“urethral“ burning is often elicited by light touch is essential in identifying those patients with ulcera-
above the urethral meatus – this is a classic finding tive disease. Cystoscopy also allows the clinician to
of BPS. Pain mapping is an essential component of the rule out other etiologies for the persistent bladder
physical exam. Patients should be evaluated for symptoms [6].

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Urodynamics Like for cystoscopy, the utility of urodynam- reserved for patients who are not responsive to
ics in BPS is ruling out other etiologies such as bladder conservative therapy with an exception for
outlet obstruction and detrusor overactivity. Therefore, patients who are discovered to have Hunner’s
if there is a question regarding the presence of these lesions.
other conditions, urodynamic testing should be per- • If there is no improvement of symptoms in
formed. Although patients with BPS have been found a clinically meaningful timeframe, diagnosis
to have common findings such as early first sensation to should be reevaulated.
void and decreased bladder capacity, these characteris-
tics are not necessary for diagnosis [15]. Evaluation of Recommendations for treatment of BPS are based
urethral pressures during urodynamics will often dem- on the American Urologic Association (AUA) guide-
onstrate urethral pressures that are elevated (greater lines for the diagnosis and treatment of BPS. The
than 130 cm H2O) in patients who have pelvic floor hierarchy of the treatment recommendations is
hypertonicity. Voiding dysfunction due to the inability based on potential benefit, risk–benefit profile, and
to completely relax the pelvic floor muscles is common severity and reversibility of adverse effects. Treatment
in patients with hypertonicity and BPS [16]. is challenging because there is no one treatment that is
reliably effective for the majority of patients.
Bladder Anesthetic Challenge Test When the clinician Therefore, a trial of multiple treatment approaches
suspects the bladder to be a source of pain, including multimodal therapy may be required before
a relatively simple anesthetic challenge will often an effective regimen is identified for an individual
demonstrate for both the patient and the clinician patient.
that at least temporary relief of pain can be achieved.
The placement of 20 mL of 2% lidocaine combined First-Line Interventions
with 20,000 units of heparin can result in at least 2
hours of marked improvement in pain when pain is All patients should be offered these interventions
originating from the bladder. This diagnostic test has when diagnosed with BPS [7].
replaced the use of potassium chloride in many prac-
tices as a test of bladder hypersensitivity and pain [17]. Patient Education (Clinical Principle)

How Is Bladder Pain Syndrome This element of treatment is important in setting
Treated? patient expectations for their disease course and
options for therapy. Patients should be counseled on
The management of BPS should be guided by the normal bladder function and BPS including the fact
following principles: that there is much still unknown about this condition.
Patients should be educated about the various triggers
• The initial treatment level should be tailored to the to their symptoms and why treatment is typically
individual patient based on severity of symptoms, multimodal. The concept of multiple pain generators
patient preference, and clinician judgment. and the need to treat each one is stressed so that the
patient understands the reasoning behind each of the
• The clinician should target each pain generator treatment modalities and gets her involved in her
and thus therapy will be individualized. Most treatment decisions. Additionally, it is important for
patients will have both bladder and pelvic floor patients to understand that BPS is a chronic condition
pain. Therapy should address both. that may have periodic flares interspersed with
asymptomatic periods.
• If in the best interest of the patient, multiple
treatments may be started simultaneously. General Relaxation/Stress Management (Clinical

• Ineffective treatments should be stopped. Principle)
• Pain management should be a central
It is well established that stress is associated with
consideration throughout treatment, as the heightened pain sensitivity. Therefore, development
ultimate goal of intervention is to minimize pain of relaxation exercises and coping mechanisms can
and therapy side effects while maximizing patient provide relief from symptoms of BPS. As this type of
function. intervention is beyond the scope of practice for most
• Treatment should be implemented from most to gynecologists, a multidisciplinary approach is recom-
least conservative. Surgical intervention should be mended with coordination of care with counselors.

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Bladder Pain Syndrome

Self-Care/Behavior Modification (Clinical Principle) improve symptoms of BPS in more than 60% of
Behavior modification typically includes appropriate patients in multiple studies [7]. Medication side
fluid management (48–64 ounces per day). Dietary effects such as sedation and nausea have been
manipulation is beneficial in approximately two observed in up to 79% of patients. These adverse
thirds of patients. Patient education concerning effects were a major reason for discontinuation of
avoidance of bladder irritants such as acidic foods, the medication, so starting patients at a low dose
alcoholic beverages, and caffeine should be reviewed. such as 10 mg daily and up-titrating to 75–100 mg
The use of over-the-counter supplements is poorly daily over time is recommended.
studied but calcium glyceryl phosphate seems to
benefit many patients with BPS. This appears to Cimetidine (Grade B Evidence) Cimetidine is a histamine
work by neutralizing the acid in certain foods and H2 antagonist. Several studies including a random-
beverages. ized controlled trial (RCT) have shown that this
medication can improve BPS symptoms, although
Second-Line Interventions no long-term follow-up data are available [7].
However, there were no adverse effects reported in
Appropriate Manual Physical Therapy Techniques (Grade trials investigating cimetidine as a potential treat-
A Evidence) ment for BPS, so it has the potential to be a low-
riskintervention. Dosing of this medication varies in
More than 80% of patients with PBS have studies from 200 mg three times daily to 300–400 mg
a component of hypertonic pelvic floor muscle dys- twice daily.
function [7]. This hypertonicity results both in void-
ing dysfunction as well as myofascial pain. The Hydroxyzine (Grade C Evidence) Hydroxyzine is a histamine
constant pressure caused by the muscles results in H1 antagonist that has been shown to improve symp-
the constant feeling of needing to urinate, which toms in some patients [7]. However, the only study
then makes the patient “hold urine” and therefore that demonstrated statistically significant symptom
tends to perpetuate the hypertonicity and pain. relief included only patients with systemic allergies.
This hypertonic dysfunction is easily identified on The existence of systemic allergies may be considered
pelvic examination as well as during the perform- when selecting patients for this medication. A large
ance of urodynamics. If pelvic floor hypertonicity number of patients reported side effects including
and pain are thought to be components then refer- short-term drowsiness and weakness. These adverse
ral to physical therapy for further evaluation and effects were considered serious by patients and were
management of this symptomatology is required. similar to side effects described by patients receiving
It is important to note that strengthening (e.g., placebo medications. In studies, patients were started
through Kegel exercises) is not the goal of pelvic on a lower dose and titrated up with regimens such as
floor physical therapy. These patients need to learn 10 mg daily increased to 50 mg over weeks and 25 mg
to relax their pelvic floor muscles and the exercise daily increased to 75 mg daily over weeks.
techniques are sometimes referred to as “reverse
Kegels.” Multiple studies have shown the benefit in Pentosanpolysulfate (PPS; Grade B Evidence) PPS is a urinary
symptom resolution through the use of manual analgesic that has been widely studied for the treatment
therapy, sometimes referred to as myofascial of BPS including multiple RCTs [7]. Results of these
release. Identification of a qualified pelvic floor studies are conflicting, but aggregations of data from all
physical therapist is important, as these providers RCTs evaluating efficacy of PPS does show that the
are not available in every community. The avail- medication significantly improves symptoms of BPS.
ability of this type of physical therapy in your Of note, there is some evidence to support that PPS is
community can be determined by a visiting www less useful in patients with ulcerative BPS. Dosing of
.womenshealthapta.org or www.pelvicpain.org. this medication is 100 mg three times daily.

Oral Medications Intravesical

Amitriptyline (Grade B Evidence) Amitriptyline is Dimethyl Sulfoxide (DMSO; Grade C Evidence) DMSO is
a tricyclic antidepressant that has been shown to a urinary tract analgesic that has resulted in
improvement in BPS symptoms in multiple studies
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103

Katherine de Souza and Charles Butrick

[7]. The medication is instilled in the patient’s Pain Management
bladder and retained for 15–20 minutes. Longer
intravesical retention of the medication is not As evidenced by the recommendations for treatment
recommended because it is associated with severe in this section, there is a large range of both pharma-
pain due to the medication’s rapid absorption into cological and surgical interventions for BPS [7].
bladder tissue. There are several regimens for these Because of the severe impact of pain on patients’
bladder instillations, although the principle is for quality of life, improvement in pain is a central aim
treatments every 2 weeks for 4–8 weeks with assess- when treating this disorder. While providers should
ment for response to therapy. Additional instilla- use treatment algorithms and work with patients to
tions can be performed as needed with the idea that find appropriate therapy, additional pain control with
there will be progressively longer intervals of pain systemic analgesics may be considered in order to
relief. There are no known significant adverse improve functionality. Again, a multidisciplinary
effects for this treatment. approach may be advantageous. Referral to anesthesia
or pain specialists for management of analgesics such
Heparin (Grade C Evidence) Heparin is an anticoagulant as narcotic pain medication can be very helpful for
that has been shown to improve symptoms of BPS providers who do not have experience with these
both when used alone and when combined with medications in chronic pain patients. Regardless of
other agents. There are several regimens that have whether the primary provider for PBS decides to
been shown to improve symptoms including provide systemic analgesics or refer to another pro-
10,000 IU heparin in 10 mL of sterile water three vider, pain management should adhere to the follow-
times a week for 3 months with retention of ing principles:
1 hour and 25,000 IU in 5 mL of distilled water
twice a week for 3 months. There are no known • Oral analgesics should be used in conjunction with
serious adverse effects; however, the risk–benefit other medications that address BPS with the aim
profile of this intervention has not been fully of minimizing the reliance on narcotics for pain
evaluated, as there are no placebo-controlled trials control. In addition to medication, psychological
available. therapy should be integrated to reduce the
requirement for narcotic pain medications.
Lidocaine (Evidence Grade B) Lidocaine is a topical anes-
thetic that has been most extensively investigated • Narcotics and other medications with high
in combination with other agents for relief of BPS potential abuse should only be prescribed by one
symptoms. Lidocaine can be administered with or provider/clinic. Pain management agreements
without alkalinization. In theory, alkalinization between patients and providers should set
should improve efficacy of treatment because it guidelines for use of these medications and how
improves the penetration of lidocaine into the they are prescribed including responsibilities that
urothelium; however, this is controversial. One of patients must fulfill in order to continue
the advantages to anesthetic-based intravesical medications.
therapy is the use of this approach not only as
a “rescue” intervention but also as one that can be • If narcotics are being used, long-acting agents are
used by the patient for maintenance therapy in preferred over short-acting narcotics except for
more severe cases or when a patient cannot easily breakthrough pain.
reach the clinician involved in the management of
her BPS. Medications should be trialed in a systematic
manner with addition and titration of one medication
Most clinicians use intravesical therapy that at a time so that efficacy of individual treatments for
involves a combination of ingredients that potentially patients can be correctly identified. Medications
provide more benefit than intravesical installations should be initiated at the lowest possible dose and
that involve only one ingredient [18]. The efficacy of increased in a stepwise manner as is appropriate
combination intravesical therapy (often referred to as based on symptoms, pain scores and patient tolerance
“bladder cocktails”) has been reported by many of medication adverse effects. This requires clinicians
authors. (See Appendix: Rescue / therapeutic cocktails to be in close contact with patients.
for bladder pain syndrome flare.)
Although pain relief is an important component of
e Cambridge Core terms of use, available at BPS management, it is important for underlying blad-
der dysfunction to be addressed concurrently in order
to improve function and decrease the need for pain

Bladder Pain Syndrome

medication. Patients should be counseled that fulguration of lesions have shown high response
adequate pain relief is the goal of pain management rates, with 80%–100% of patients experiencing
as complete pain relief is not always possible. improvement in both pain and bladder function.
The treatment effect lasted for up to 23 months in
Third-Line Interventions these studies. One serious adverse effect unique to
laser fulguration is possible delayed bowel perforation
Cystoscopy with Hydrodistention (Evidence Grade C) due to scatter of laser to the bowel. Regardless of
method of fulguration, patients should be counseled
If more conservative therapies have failed, cystoscopy that they may require repeat treatment, approxi-
with hydrodistention under anesthesia can be con- mately 46% in laser studies.
sidered if one has not been done in the recent past
[7]. This procedure allows for visual inspection of the Treatment of Hunner’s lesions with intralesional
bladder epithelium for any abnormalities including steroid injections is advocated by some clinicians.
Hunner’s lesions and to rule out the possibility of Submucosal injection of triamcinolone using either
other pathology that might explain the persistent 10 mg/mL concentration or 40 mg/mL concentration
symptoms. Management of Hunner’s lesions is dis- with a maximum total injection of 60 mg triamcino-
cussed in the text that follows. The bladder capacity lone is recommended. Larger doses of triamcinolone
determined at the time of cystoscopy with hydrodis- have been studied but are not recommended because
tention is also thought to be a prognostic indication of of a lack of high-quality safety information. This
patients who are at risk for poor response to trad- intervention has yielded symptom relief from 7 to 12
itional therapies. Volume under anesthesia of less months in studies.
than 300 mL is a sign of severe disease.
Fourth-Line Interventions
Hydrodistension can be a helpful diagnostic tool
as well as a therapeutic intervention. Its use solely as Neuromodulation (Grade C Evidence)
a diagnostic tool for cannot be recommended [7].
Ideal hydrodistension has yet to be determined but Use of permanent sacral or pudendal neurostimula-
most authors advocate low-pressure, from 60 to 80 cm tion devices is not FDA-approved for BPS; however,
H2O with a duration of less than 10 minutes, although sacral neurostimulator devices are approved for man-
longer duration low-pressure hydrodistension has agement of urinary frequency [7]. Regarding sacral
been used by some providers. The duration of symp- versus pudendal nerve stimulation, a single random-
tom relief is variable across multiple studies. The ized crossover trial did show patient preference
major adverse effects experienced by patients in toward pudendal nerve stimulation. Overall, there is
these studies were temporary flare of symptoms and a relatively high response rate to implants, from 66%
rare episodes of bladder rupture. Providers and to 94%. Patients with BPS appeared to have a higher
patients must determine if the benefit of hydrodisten- incidence of implant site pain requiring revision of
sion is worth the risk of a short-term increase in pulse generator site or even removal. In recent studies,
symptoms. removal of devices occurred in up to 28% of patients
due to low efficacy of treatment or intolerable side
Treatment of Hunner’s Lesions (Grade C Evidence) effects. There are multiple cohort studies in the litera-
If identified, Hunner’s lesions can managed at the ture, while not typically randomized and often with
time of cystoscopy via either fulgration or steroid follow-up of 1 year, showing symptom improvement
injection [7]. Fulguration can be achieved via laser including urinary frequency, pelvic pain, and voiding
or electrocautery and this intervention has shown dysfunction [19].
significant improvement in pain, including complete
resolution of pain, in more than 75% of patients. Fifth-Line Interventions
Patients also experienced relief from urinary fre-
quency. The duration of effectiveness for fulguration Intradetrusor Botulinum Toxin A (Grade C Evidence)
of Hunner’s lesions is not clearly defined. Adverse
effects from this intervention are rare but do include Botulinum toxin A (BTX-A) can be used either alone
the rare risk of bladder perforation and need for or in conjunction with hydrodistension [7]. There is
subsequent repair. Similarly, studies on laser not strong evidence to support recommendation for

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Katherine de Souza and Charles Butrick

or against contaminant treatment with bladder hydro- Sixth-Line Interventions
distension. Studies have shown up to 86% efficacy for
BTX-A; however, almost all patient experienced return Major Surgery (Evidence Grade C)
to baseline pain and function after a certain time inter-
val, commonly 3 months. There is a range of intervals Surgical management of BPS should be reserved for
between repeat treatments as well as a range of locations patients with severe disease that has been unrespon-
for injection including the trigone alone, the bladder sive to other treatments [7]. Surgical interventions are
walls alone, and a combination of both. No definitive irreversible and lead to significant changes in lifestyle
recommendation for site of bladder injection of BTX-A that patients may not wish to undertake considering
exists. The recommended dose is 100 U BTX-A, as there that they may not experience symptoms relief follow-
are significant potential adverse effects that increase with ing surgery even if the bladder is completely removed.
higher doses. Adverse effects include dysuria as well as The likelihood of favorable outcomes can be increased
urinary retention. Retention can range from mild, by carefully selecting the patients to whom these pro-
requiring abdominal straining in order to void, to severe cedures are offered. Patients who have small bladder
with the need intermittent self-catheterization. These capacity under anesthesia and failed to improve with
effects generally resolved in 1 to 3 months, but in some more conservative measures are most likely to benefit
cases, they persisted. Patients should be thoroughly from surgery. Additionally, patients with little or no
counseled and accept the risk of severe urinary retention neuropathic pain are more likely to experience symp-
requiring self-catherization prior to use of BTX-A. tom relief from surgery.
Additionally, patients with known urinary retention
may not be good candidates for this therapy given the Diversion with or without Cystectomy This procedure
adverse effect profile. involves diversion of urine to an alternative to the
bladder such as an ileal conduit. Because of the
Cyclosporin A (Grade C Evidence) possibility of persistent pain following removal of
the bladder, cystectomy may or not be performed at
Cyclosporine A (CyA) is an immunosuppressive the time of diversion. Creation of a diversion has the
agent that has been shown to be particularly effective potential to effectively improve urinary frequency, so
for patients with ulcerative BPS [7]. The recom- patients for whom this is a major complaint may be
mended dose is 2–3 mg/kg/day in two divided good candidates if they have failed conservative
doses with a maximum dose of 300 mg daily. If measures.
symptom control is established yet side effects such
as an increase in blood pressure or creatinine occur, Substitution Cystoplasty : This procedure involves excis-
some patients will require a reduction in dose. ing a portion of the bladder thought to be contribut-
A dose reduction to as little as 1 mg/kg/day should ing to BPS. In some cases, the trigone is excised while
be considered. Clinicians should carefully follow the in other cases it is preserved. The benefit of trigone
concerning side effects, which include hypertension excision is that the area is thought to be a source of
and deterioration of renal function. In a trial com- pain and is a common location for Hunner’s lesions;
paring CyA to pentosanpolysulfate, 75% of patients however, trigone excision increases the risk of urinary
experienced improvement of symptoms in 6 months retention, requiring chronic self-catheterization.
with CyA. Other studies have shown that this medi- Patients with Hunner’s lesions and small bladder cap-
cation is effective in as little as 6 weeks, with 87% of acity under anesthesia are more likely to benefit from
patients reporting markedly improved urinary func- substitution cystoplasty. Patients who identify the
tion and resolution of pain. While adverse effects are urethra as their main site of discomfort are less likely
quite common, present in 94% of patients in one to benefit.
study, most are minor. Serious adverse effects
include hypertension, renal impairment, and cuta- Treatments That Should Not Be Offered
neous lymphoma. Therefore, the use of this medica-
tion should be done with carefully performed Although there is no reliable intervention that will
informed consent as well as a program of close fol- improve the BPS for every patient, several therapies
low-up especially as it relates to blood pressure and have shown no benefit and should not be offered to
renal function changes. patients because the risk of the intervention out-
weighs potential benefits.

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Bladder Pain Syndrome

• Long-Term Antibiotics (Grade B Evidence) symptoms although there was significant placebo
Antibiotics should be reserved for patients with effect as well. Activation of SH2-containing inositol-
positive urine cultures. There has not been any 5΄-phosphatase 1, P2X3 receptor antagonists, and α1
benefit to antibiotic therapy for bladder pain of adrenoceptor antagonists is also under investigation
noninfectious etiology. Given the serious potential and has shown success in improving symptoms of
adverse outcome of antibiotic resistance, this BPS. These potential treatments may have a systemic
therapy should not be offered [7]. effect addressing neurogenic inflammation. There are
also trials of bladder treatments such as intravesical
• Intravesical Bacillus Calmette-Guérin (BCG; liposomes and toll-like receptor antagonists. These
Grade B Evidence) There have been several two areas of study would affect only the symptoms
studies that demonstrated no significant of BPS that arise from the bladder itself and not
difference between BCG instillation and placebo. address symptoms due to central sensitization [5].
Because there is no evidence of benefit and there
have been serious adverse effects such as sepsis Summary
and death associated with BCG, this therapy
should not be offered [7]. Bladder pain syndrome affects approximately 5% of
all women. As our understanding of this pain disorder
• High-Pressure Long-Duration Hydrodistension advances we now realize that patients can present with
(Grade C Evidence) There has been no reliable many clinical phenotypes. Some will present with
benefit to performing hydrodistension at isolated bladder symptoms but some will present
pressures greater than 80 to 100 mm H2 with a history of various types of chronic pain dis-
O. Similarly, longer durations of hours or repeated orders with multiple pain generators. Given our
30-minute intervals have shown no reliable understanding of centralized pain, the management
benefit. However, these interventions place of this visceral pain syndrome requires that the clin-
patients at greater risk for complications such as ician identify each pain generator, and using
sepsis and bladder rupture. Therefore, this a multimodal approach, attempt to downregulate
technique of hydrodistension is recommended each component of the pain using the therapeutic
against [7]. options that we have discussed. Most patients will
benefit from this approach, especially if identification
• Long-Term Systemic Glucocorticoid of BPS and initiation of therapy are undertaken in
Administration (Grade C Evidence) Although a timely fashion. As with any pain disorder, the longer
studies have shown that this intervention can the delay in the diagnosis and initiation of therapy the
provide symptoms relief, long-term steroid use is more difficult it will be to manage.
associated with diabetes, hypertension, and
immunocompromise. For this reason, this Five Things You Need to Know
treatment is not recommended [7].
• Hallmarks of bladder pain syndrome (BPS) are
Experimental/Future bladder pain and urgency in the setting of
frequent small-volume voids for the purpose of
Many current studies are focusing on whether it is pain relief.
beneficial to “phenotype” individuals with BPS in
order to more effectively guide treatment regimens. • This condition causes severely diminished quality of
There are several investigatory treatments that are life but is frequently underdiagnosed by clinicians
targeting immune modulation that contribute to despite simple clinical criteria for diagnosis.
bladder inflammation. Nerve growth factor (NGF) is
more common in animal models, and anti-NGF with • Although all patients should be offered education,
monoclonal antibodies is one of the treatments cur- stress management, and behavioral modification
rently under investigation. Although studies in as first-line treatment, no single reliable
humans have not shown significant improvement, pharmaceutical or surgical intervention will work
larger population studies may reveal this to be an for all patients. Treatments should be
effective treatment. Likewise, antitumor necrosis fac- individualized based on assessment of active pain
tor-α (TNF-α) is under investigation using adalimu- generators. Most patients with BPS have both
mab to block the cytokine’s proinflammatory effect. bladder and pelvic floor myofascial components
Treatment revealed significant improvement in to their pain.

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Katherine de Souza and Charles Butrick

• The goal of therapy is to identify triggers to 9. Berry SH, Elliott MN, Suttorp M, et al. Prevalence of
their pain disorder and to treat each pain symptoms of bladder pain syndrome/interstitial
generator. Most patients will have marked cystitis among adult females in the United States.
improvement in symptomatology but J Urol. 2011;186(2):540–4. DOI: 10.1016/j
intermittent flares are common even after .juro.2011.03.132
appropriate therapy.
10. Clemens JQ, Meenan RT, Keeffe MCO, Kimes T,
• While ulcerative IC is relatively rare, Calhoun EA. Costs of interstitial cystitis in a managed
approximately 4%, it represents a unique form care population. Urology. 2008;71(5):776–81. DOI:
and typically is associated with persistent 10.1016/j.urology.2007.11.154.COSTS
symptoms despite appropriate therapy.
Cystoscopy is required to identify and treat 11. Mazurick CA, Landis JR. Evaluation of repeat daily
active Hunner’s lesions. voiding measures in the national interstitial cystitis
data base study. J Urol. 2000;163(4):1208–11. DOI:
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.ucl.2012.06.007 urogynaecology. Geburtshilfe Frauenheilkd. 2017;77
(12):1299–1303.
4. Jhang J, Kuo H. Pathomechanism of interstitial
cystitis/bladder pain syndrome and mapping the 15. Kuo Y-C, Kuo H-C. The urodynamic
heterogeneity of disease. Int Neurourol J. 2016;20 characteristics and prognostic factors of patients with
(Suppl 2):S95–S104. interstitial cystitis/bladder pain syndrome.
Int J Clin Pract. 2013;67(9):863–9. DOI: 10.1111/
5. Andersson KE, Birder L. Current pharmacologic ijcp.12116
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Int Neurourol J. 2017;21(4):235–42. DOI: 10.5213/ 16. Butrick C, Sanford D, Hou Q, Mahnken J. Chronic
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and urothelial observations. Int Urogynecol
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.urology.2005.04.011 17. Evans RJ, Sant GR. Current diagnosis of interstitial
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bladder pain syndrome. J Urol. 2011;185 18. Cvach K, Rosamilia A. Review of intravesical
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.nec.2013.08.001

e Cambridge Core terms of use, available at

Bladder Pain Syndrome

Appendix

To help your physician determine if you have interstitial cystitis, please put a check mark to the
most appropriate response to each of the questions below. then add up the numbers to the left of the
check marks and write the total below.

Symptom index Problem index

During the past month: During the past month, how much has each
following been a problem for you?
Q1. How often have you felt the strong need
to urinate with little or no warning? Q1. Frequent urination during the day?
0. Not at all. 0. No problem.
1. Less than 1 time in 5. 1. Very small problem.
2. Less than half the time. 2. Small problem.
3. About half the time. 3. Medium problem.
4. More than half the time. 4. Big problem.
5. Almost always.
Q2. Getting up at night to urinate?
Q2. Have you had to urinate less than two hours 0. No problem.
after you finished urinating? 1. Very small problem.
2. Small problem.
0. Not at all. 3. Medium problem.
1. Less than 1 time in 5. 4. Big problem.
2. Less than half the time.
3. About half the time. Q3. Need to urinate with little warning?
4. More than half the time.
5. Almost always. 0. No problem.
1. Very small problem.
Q3. How often did you most typically get up 2. Small problem.
at night to urinate? 3. Medium problem.
0. None. 4. Big problem.
1. Once.
2. Two times. Q4. Burning, pain, discomfort, or pressure in your
3. Three times. bladder?
4. Four times. 0. No problem.
5. Five or more times. 1. Very small problem.
2. Small problem.
Q4. Have you experienced pain or burning 3. Medium problem.
in your bladder? 4. Big problem.

0. Not at all. Add the numeric values of the checked entries:
1. A few times. total score:
2. Almost always.
3. Fairly often.
4. Usually.

Add the numeric values of the checked entries:
total score:

Figure 9.1 O’Leary-Sant symptom screener.

at 20:21:51, 109

Katherine de Souza and Charles Butrick

PELVIC PAIN and URGENCY/FREQUENCY
PATIENT SYMPTOM SCALE

Patient’s Name: Today’s Date:

Please circle the answer that best describes how you feel for each question,

01 2 34 SYMPTOM BOTHER
11-14 15-19 20+ SCORE SCORE

1 How many times do you void during the 3-6 7-10 2 3 4+
waking hours? Moderate Severe
15-19
2 a. How many times do you void at 01
night?

b. How many times do you void so

what extent does it usually bother None Mild

you?

3 Are you currently sexually active.

YES NO

4

a. IF YOU ARE SEXUALLY Never Occasionally Usually Always
ACTIVE, do you now or have
you ever had pain or symptoms
during or after sexual intercourse?

b. Has pain or urgency ever made Never Occasionally Usually Always
you avoid sexual intercourse? Never Occasionally Usually Always

5

Do you have pain associated with your
bladder or in your pelvis (vagina, lower
abdomen, urethra, perineum)?

6 Do you still urgency shortly Never Occasionally Usually Always
after urinating? Mild Moderate Severe

7 a. If you have pain, is it usually Never Occasionally Usually Always
Mild Moderate Severe
b. How often does your pain bother
you? Never Occasionally Usually Always

8 a. If you have urgency, is it usually

b. How often does your urgency
bother you?

SYMPTOM SCORE (1, 2a, 4a, 5, 6, 7a, 8a)
BOTHER SCORE (2b, 4b, 7b, 8b)

TOTAL SCORE (Symptom Score + Bother Score) =

Figure 9.2 Pelvic pain and urgency/frequency patient symptom scale.

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Bladder Pain Syndrome

Therapeutic Cocktail for Bladder Pain Syndrome Flare

Supplies: • 3mL syringe
• 18 gauge needle
• Lidocaine 2% – 20mL • #8 French Pediatric feeding tube
• 1mL Triamcinolone 40mg/1mL • 10mL Lidocaine Hydrochloride
• 1mL Heparin Sodium 20,000
Jelly USP, 2%
units/mL
• Catheter Tray
• 30mL syringe

Procedure:
• Draw up 20mL of Lidocaine in 30 mL syringe
• Draw up 120mL of Triamcinolone in 3 mL syringe followed by 1mL of Heparin
• Inject into 30mL syringe
• Explain procedure to patient
• Have patient void before procedure

If symptoms of bladder infection present, dipstick urine to rule out infection
If positive do not proceed, if negative proceed
While patient is in Lithotomy position, open catheter tray and supplies
Cleanse labia and urethra for catheterization
Insert small amount of Lidocaine Jelly to use as lubricant, can use regular
lubricant
Insert Pediatric catheter – check for post void residual
• Then inject Appell Cocktail slowly
• Pull catheter out
• Instruct to try not to void for 2 hours

May reschedule weekly or up to three times week if needed. Average is 6 weeks
of treatment and then as needed

Figure 9.3 Rescue/therapeutic cocktails for bladder pain syndrome flare. When patients have a flare in their bladder symptoms the clinician
should always consider the possibility that they have a bladder infection. Also in the differential is a flare of myofascial pain that often
accompanies BPS. After evaluation, if a component of a flare is thought to be due to bladder pain, a rescue cocktail should be administered. The
patient’s response to this will also clarify for the patient and the clinician if the bladder is a significant pain generator at this time. This can also
be used during the initial evaluation of the patient’s symptoms of pelvic pain, to determine if the bladder is involved.

at 20:21:51, 111

Chapter Pelvic Pain Arising from Pelvic Congestion

10 Syndrome
Nita Desai and Mark Dassel

Editor’s Introduction pelvic pain in the 1940s–50s, is now a well-
characterized etiology of PCS [2]. PCS typically
Pelvic congestion syndrome is another condition affects women of reproductive age. Worldwide,
causing pelvic pain for which there is no consensus on rates of CPP, for women of childbearing age, range
diagnosis or treatment; moreover, some physicians from 14% to 43% [2, 3]. CPP rates in the United
don’t even believe it causes pelvic pain. Pain from States are approximately 15% for women of child-
pelvic congestion is multifactorial and may be caused bearing age [4]. Congested pelvic veins can be quite
by hypoxia and mechanical stretching of pelvic veins. painful and can account for a range of 10%–40% of
It usually occurs after pregnancy (may be full term, cases of CPP [1,2,5]. No cases have been reported in
ectopic, or miscarriage) and presents as a sensation of postmenopausal women [5].
heaviness in the lower abdomen with upright body
position. On the background of this sensation there is Anatomical Considerations
intermittent sharp lower pelvic pain. In our practice we
diagnose pelvic pain based on symptoms but confirm The complex arena of venous circulation of the female
it with transfundal venography preformed in the pelvis must be considered when evaluating patients for
operating room immediately prior to surgery. We treat PCS, as these plexuses are uniquely interconnected: the
pelvic congestion syndrome either by referring the left renal and ovarian veins, the iliac veins (common,
patient to interventional radiology for embolization of external, and internal), and the lower extremity veins. In
the pelvic veins or by surgical selective pelvic vein addition to communications between these systems,
ligation. In this procedure we separate ovarian veins there is also frequent crossover, from side to side. In
from arteries and ligate them and any significantly the female pelvis, the ovarian veins drain blood flow
enlarged veins in the broad ligament. Outcomes from from the parametrium, cervix, mesosalpinx, and pampi-
this treatment are effective; however, pain and niform plexuses, which may also drain through the
congestion may return with time, especially if the internal iliac as a collateral pathway [6]. These plexuses
patient becomes pregnant again. form the ovarian vein, which may have two to three
trunks before becoming a single trunk at the level of L4–
Introduction L6. The ovarian vein has a mean diameter of approxi-
mately 3 mm, which increases with pregnancy, and
Pelvic congestion syndrome (PCS), also known as usually has two or three valves, which are incompetent
pelvic venous insufficiency, is a chronic condition in about 50% of women [6]. Although variations may
causing pelvic pain. PCS occurs when varicose veins occur, the right ovarian vein usually drains directly into
develop around the ovaries in the setting of chronic the inferior vena cava (IVC), whereas the left drains into
pelvic pain (CPP). Similar to varicose veins in the legs, the left renal vein. The ovarian veins collateralize exten-
pelvic varicosities are thought to result from sively with the ascending lumbar and peritoneal veins
a combination of dysfunctional venous valves, retro- [5]. The internal iliac veins receive inflow from the
grade blood flow, and venous engorgement [1]. utero-ovarian, vesicular, hemorrhoidal, and sacral ven-
ous plexuses [5]. The two systems, the ovarian, and
Prevalence internal iliac veins, run together in the broad ligament
with extensive communication [5].
PCS, or pelvic venous insufficiency, initially
described around the 1850s, and correlated with

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Pelvic Pain Arising from Pelvic Congestion Syndrome

Pathophysiology bladder syndrome, spastic pelvic floor syndrome, and
others. Typical features are shown in Table 10.1 [5].
Insufficiency of the pelvic veins arises when there is
abnormal dilation or distention of the venous terri- In a patient with characteristic symptoms, the
tories between the iliac and ovarian veins. While the diagnosis is supported by bimanual examination
precise etiology of PCS remains uncertain, it is likely exhibiting cervical motion tenderness, uterine tender-
multifactorial. Valvular insufficiency, venous obstruc- ness, and/or ovarian tenderness. However, patients
tion, and hormones all may play a role in the develop- can also have no pain on exam. A study by Beard
ment of congestion of the pelvic veins [5]. The cause reported the combination of tenderness on abdominal
of pain due to the pelvic congestion remains unclear, palpation over the adnexa compounded by a history
but the most likely possibility is that increased dilata- of postcoital ache was 94% sensitive and 77% specific
tion, concomitant with stasis, leads to the release of for discriminating pelvic congestion from other
local pain-producing substances [5]. Insufficiency can causes of pelvic pain [5, 7]. Unfortunately, no clear
be delineated further into primary/intrinsic causes diagnostic algorithm exists for PCS, and therefore
and secondary/extrinsic causes. a multidisciplinary approach for pelvic pain, utilizing
gynecological, urological, vascular, or interventional
Primary venous insufficiency occurs due to either radiological input may be helpful. Imaging should be
the absence of venous valves or the incompetence of performed to support but not define diagnosis, espe-
such valves. Congenital absence of ovarian vein valves cially given that incompetent and dilated ovarian
has been shown in 13%–15% of patients on the left veins are common, nonspecific findings. Further,
side and in 6% on the right side [5]. Venous valves are although dilatation of the ovarian vein is necessary
incompetent in 41%–43% of women on the left side, but not sufficient for diagnosis, there is no consensus
and in 35%–46% on the right side [5]. There is higher on the optimum cut-off for ovarian vein diameter in
prevalence of PCS in multiparous women, which may PCS and no validated measures for venous congestion
be related to the 50% increase in pelvic vein capacity and tortuosity. Furthermore, the reported cut-off val-
during pregnancy [5]. This phenomenon can result in ues for ovarian vein diameter differ between the
valvular incompetence as well as retrograde blood imaging techniques [5].
flow. These changes may persist for up to 6 months
following pregnancy [5]. Predisposing risk factors for the development of
PCS are those of most women alive today: being of
Secondary pelvic vein incompetence is related to reproductive age. Pregnancy and its changes on total
venous outflow obstruction by extrinsic compression. blood volume, and the distribution of said volume, are
Possible causes are nutcracker syndrome, wherein the an obvious predisposing factor. However, there are
left renal vein is compressed due to entrapment cases of PCS in patients without prior pregnancy. This
between the abdominal aorta and the superior mes-
enteric artery, or May–Thurner syndrome, in which Table 10.1 Common symptoms of pelvic congestion
the left common iliac vein is compressed by the right syndrome
internal iliac artery [5]. Rarely, PCS may develop from
regional venous overload from congenital venous and Noncyclical pain for at least 3–6 months
arteriovenous malformations due to cirrhosis, retro-
aortic left renal vein, tumor thrombosis of the inferior Pain presenting during or after pregnancy, with worsening
vena cava, portal vein thrombosis, and renal cell car- pain with subsequent pregnancies
cinoma with left renal vein thrombosis [5].
Unilateral dullness, achiness, and/or heaviness sensations; can
Diagnosis be present bilaterally or alternate sides

A thorough history and physical examination are Pain aggravated before or during menstrual bleeding because
paramount to achieve proper diagnosis in the case of of any factor leading to increased intraabdominal pressure
PCS, especially given that patients with incompetent such as standing for long periods of time, walking, lifting,
pelvic veins can be asymptomatic. Other causes of and postural changes
pelvic pain, both chronic and acute, should be ruled
in or out based on the clinical history, such as, but Pain worse during or after intercourse
not limited to, ovarian torsion, endometriosis, painful
Pain least severe at start of day, worse at end of day
at 20:21:52, .011
Symptom improvement by lying in supine position

Pain takes several hours to subside

Possible presence of vulvovaginal, gluteal, perineal, or lower
limb varicosities

113

Nita Desai

may be due to intrinsic issues with the veins, or ovarian vein dilation, and compression of iliac and
lifestyle choices in which intraabdominal pressure renal veins [5]. Unfortunately, CT requires radiation,
is routinely increased, such as patients who must and neither modality provides hemodynamic infor-
stand for prolonged periods of time, routinely lift mation, a clear benefit of duplex ultrasonography.
heavy objects, or engage in extreme sports, such as Duplex ultrasound has become the diagnostic test of
skydiving or bungee-jumping. In all these cases, choice in most venous centers [6]. Additionally, as
increased intraabdominal pressure is common these two modalities typically require the patient to
denominator. However, we must note here the effect be positioned in the supine position, there is concern
of estrogen, which can act as a vasodilator, causing for less specificity of results.
smooth muscle relaxation and loss of vascular
responsiveness [5]. This effect may explain why Laparoscopy is often performed in patients with
these symptoms improve with time and the parallel pelvic pain. The rate of any pathological findings
decline of estrogen, as there is complete regression of at time of laparoscopy, in women with CPP, is
symptoms after menopause [5]. 35%–83%, however, the rate of PCS seen at time of
laparoscopy is 20% [5]. PCS is likely to be missed at
Imaging the time of laparoscopy due to CO2 insufflation and
Trendelenburg position causing venous collapse [5].
Ovarian venography is, and has been, the gold stand- Therefore, laparoscopy should not be considered
ard for diagnosis [6]. Initially published by Beard et al. a first-line diagnostic tool for PCS [5].
in 1984, these criteria included ovarian diameter of
6 mm or greater, contrast retention in the pelvic Table 10.2 summarizing these imaging modalities
venous plexus of more than 20 seconds, congestion as described by Borghi et al details these issues.
of the pelvic venous plexus and/or opacification of the
ipsilateral (or contralateral) internal iliac vein, and/or Complications/Fertility
filling of vulvovaginal and thigh varicosities.
There is scant information in the literature regarding
Each variable was assigned a value of 1 to 3, rate of pregnancy and associated outcomes after treat-
depending on the degree of abnormality, with ment for PCS, regardless of modality. The procedure
a score greater than 5 indicating PCS [7]. A benefit appears to do no harm to ovarian function, as no
of contrast venography is that the tool is both diag- significant differences in hormone levels were
nostic and therapeutic, after which sclerotherapy or observed before and after therapy [8]. Additionally,
embolization may be performed. These treatments reports about pregnancy and ovary hormone levels
will be discussed later in the chapter. However, after embolization are also rare [8]. Further studies
numerous less invasive imaging options are available. are warranted.

Ultrasound Treatment

Ultrasound imaging is the least invasive imaging test- PCS is as enigmatic to treat as it is to diagnose;
ing available to date. It is helpful in that it can thor- however, many reported successful treatments have
oughly evaluate pelvic anatomy, as well as include or shown varying degrees of efficacy. Treatments range
exclude other etiologies of pain. PCS can be suspected from hormonal to a variety of surgical and nonsurgi-
in patients with dilation of ovarian vein greater than cal procedures. Moreover, as PCS is a vascular dis-
4 mm, reversed or retrograde blood flow, slow blood order found in the pelvis, traditionally separated
flow (<3 cm/second), presence of tortuous and or specialties have each developed unique approaches
dilated veins, dilated arcuate veins crossing the uter- to the condition, including treatment from gyne-
ine myometrium, or variable duplex waveform in the cology, vascular surgery, and interventional radi-
varicoceles during Valsalva maneuver [5]. However, ology. It should be kept in mind that as PCS is often
the ability to obtain such detail is operator dependent, found concurrently with other pelvic pain related
so further workup may be warranted. disorders (i.e., endometriosis, high-tone pelvic floor
dysfunction, centralized pain syndromes, among
Both CT and MRI offer detailed cross-sectional others), treatment options will vary in regard to out-
imaging of both anatomy and pelvic vasculature. come. Therefore, a thorough pelvic pain workup
Both modalities are sensitive for pelvic varices, should be completed so the correct disease will be

e Cambridge Core terms of use, available at
.011

Pelvic Pain Arising from Pelvic Congestion Syndrome

Table 10.2 Advantages and disadvantages of various radiological tests performed in patients with pelvic congestion syndrome

Technique Pros Cons
US
First-line screening tool False positives
CT Exclude other causes False negatives
Noninvasive Operator dependent
No radiation Technically difficult

Detailed anatomical overview Radiation exposure
Exclude other causes Low specificity
Expensive
MRI Detailed anatomical overview Intervention not possible
Exclude other causes
Venography No radiation Low specificity
Laparoscopy Expensive
Gold standard Intervention not possible
Intervention possible
Radiation exposure
Detailed anatomical overview Invasive
Exclusion of other causes
Intervention possible Invasive
Expensive
Low specificity
CO2 insufflation and Trendelenberg may cause vein collapse

specifically treated. The generally complicated and versus control groups. There was also a corresponding
multifaceted nature of chronic pelvic pain syndromes decrease in monthly quantified blood loss from 204
can make evaluating treatment efficacy of a single mL to 90 mL on a pictorial menstrual blood loss tool
disease process difficult, as unintended treatment of [10]. This could suggest that a decreasing duration of
concurrent syndromes can alter important outcome dysmenorrhea symptoms may have been the major
measures. Keeping this in mind, there is much pub- contributor to pain improvement [10].
lished data regarding treatment for PCS, and many
interventions have been shown to be effective in the The efficacy of these hormonal medications may
treatment of this condition. also be linked to interruption of the menstrual cycle,
since there are known changes to both uterine and
Medical Therapies ovarian blood flow during the course of the menstrual
cycle [12].
Progestins have shown benefit in the treatment of PCS
with regard to decreased congestion of vessels on Similarly, goserelin acetate, a gonadotropin-
ultrasound and relief of pain, likely via partial sup- releasing hormone (GnRH) agonist, has shown effi-
pression of ovarian function [9]. Though the exact cacy in the treatment of PCS. This medication also
mechanism of action is unknown, the treatment induces amenorrhea, but perhaps the blockage of the
seems to be paradoxical because progestins are sus- hypothalamic–pituitary–adrenal (HPA) axis and sub-
pected to be responsible for dilation of blood vessels sequent decrease in overall female hormone levels
in bodily processes, particularly during pregnancy. plays a role. This theory may be supported by evi-
Nevertheless, oral progestin-only contraceptives, as dence that PCS seems to resolve in postmenopausal
well as the etonogestrel implant, have both demon- women [10] with the decrease in estrogen, which has
strated efficacy in the treatment of pain in women been proposed to be a venous dilator [11]. In
with PCS [9–11]. Of note, in one study, both patient a randomized controlled trial comparing goserelin
satisfaction and pelvic venography scores improved acetate to medroxyprogesterone acetate, goserelin
with etonogestrel implant at 1 year [10]. At 6 months, acetate was superior with respect to pelvic venog-
pain scores with the implant decreased from a visual raphy, sexual functioning, anxiety, and depressive
analog score (VAS) of 7.7 to 4.6, and 83% of women states, as well as pelvic symptoms score (a scale
were satisfied to very satisfied with the result [10]. including pelvic pain, dyspareunia, dysmenorrhea,
Objective repeat per-uterine venography scores and pelvic tenderness on exam) [11]. Other medical
improved, decreasing 4.5 points from 8.6 in treatment treatments that may show some efficacy for the treat-
ment of PCS include danazol, phlebotonics, dihy-
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115

Nita Desai

drugs (NSAIDs), but there is a paucity of data on these sclerosants are liquid and not radiopaque, to better
treatments [13]. control placement, many interventionalists treating
PCS will use them in conjunction with embolic agents,
One consistent issue with medical treatment is the which can be better visualized on imaging and deployed
return of symptoms upon patient discontinuation of more specifically [15]. For this reason, embolization
therapy. When patients are peri-menopausal or are agents are typically used in larger vessels with the
willing and able to use these medications as long- added advantage of radio-opacity to localize their place-
term therapy, this treatment course can be highly ment more precisely. These agents include vascular
successful. However, many of these medications coils, Amplatzer plugs (nitinol mesh), and microembolic
have side effects. Progestins, namely medroxyproges- particles, among others [15]. In the literature, transcath-
terone acetate, have been associated with mood eter embolization may be used to describe an interven-
changes, emotional lability, headaches, abnormal tional procedure that includes the use of both
uterine bleeding, and a variety of other symptoms a sclerosing and embolic agent [16]. Selection of
[14]. When a patient requires this medication for a specific agent is provider dependent and can depend
a short period of time, or there is an absence or limited on vessel size, desire for permanence of effect, and
side effects, it may make sense for her to continue this whether or not cell death is desired [15]. The Society
treatment course. Goserelin acetate also may develop for Vascular Surgery and the American Venous Forum
issues of intolerability, producing side effects linked to “suggest treatment of pelvic congestion syndrome with
a low estrogen state, for example, hot flashes, night coil embolization, plugs, transcatheter sclerotherapy can
sweats, emotional lability, vaginal dryness, with be used alone or together” [17].
resulting dyspareunia [14]. Furthermore, goserelin
acetate is not indicated for long-term use, as the low The mainstay of interventional radiologic treatment
estrogen state it induces can lead to decreased bone of PCS is transcatheter embolotherapy (TCE).
mineral density. One should balance the quality of life Introduced for the treatment of PCS in the early 1990s
considerations related to medication side effects ver- by Edwards et al. [18], the procedure has been modified
sus those associated with pain relief, as well as patient from a unilateral approach to include bilateral embol-
desires for future fertility. ization of ovarian veins using coils and sclerosant foam,
either from a jugular or femoral approach [19]. With the
Procedural Interventions left-sided unilateral approach, approximately one-third
of patients reported no or only partial relief; however,
When conservative medical therapy fails, there are the bilateral approach has excellent success rates [19].
a variety of effective procedures that can be con- The procedure is technically successful 98% of the time
sidered. These have the advantage of not having the and efficacious in decreasing pain in 65%–85% of
long-term side effects of medical management; how- patients with recurrence rates of 8% [19]. A trial of long-
ever, they are not free of risk. Procedural interven- term follow up showed that 83% of patients had clinical
tions are either radiologically directed or surgical improvement 4 years post-procedurally [20]. TCE is
procedures performed under general anesthesia. generally low risk related to complications, ranging
from 3% to 8%, and can include foam or coil migration;
Physicians trained in interventional radiology can recurrence of varices; and thrombophlebitis, gonadal
perform a variety of therapies with the aim of obliterat- vein perforation, or cardiac arrhythmia [13]. A 2016
ing the dilated, dysfunctional pelvic veins associated systematic review of 22 studies (n = 1,308 patients)
with PCS, typically the ovarian and iliac veins, targeting reported significantly decreased pain scores on a visual
the plexuses around the uterus itself. Treatment for PCS analog scale (VAS) with a follow-up of at least 12
has historically involved placement of endothelial scler- months [16].
osing or embolic agents by accessing pelvic venous
structures through entry points in the femoral, jugular, Overall, the interventional radiologic approach
or radial arteries [15]. Sclerosing agents produce occlu- using TCE is beneficial in that it is very effective, has
sion by causing severe inflammation and thrombosis, a low risk profile, and can be performed concomi-
some inducing immediate endothelial cell death. As tantly with the procedure that confirms the diagnosis
a result, these agents act immediately and irreversibly, of PCS. Furthermore, its long-term success rate and
and include absolute alcohol, sodium tetradecyl, ethyl- rapid return to full function for patients makes it an
ene vinyl alcohol (Onyx), and other agents [15]. Because attractive therapy for the treatment of PCS.

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Pelvic Pain Arising from Pelvic Congestion Syndrome

Surgical Procedures shown to have endometriosis [24]. As a result, surgical
intervention has relevance among the current treat-
A variety of surgical therapies have been used to treat ment modalities. Additionally, some authors suggest
PCS with positive results. These procedures range surgical intervention may be further indicated when
from ovarian vein ligation to extirpative therapies the etiology of PCS is obstructive, such as in May–
such as hysterectomy, with or without bilateral sal- Thurner syndrome, or nutcracker syndrome [25]. In
pingo-oophorectomy (BSO). these circumstances, treatments with embolotherapy
or sclerotherapy may not be as effective because these
Studies have shown efficacy with regard to min- treatments focus on the incompetent valves and not
imal impact laparoscopic procedures such as ovarian the anatomical obstructive etiology [25].
vein ligation procedures, efficacy shown both with
ligation near the infundibulopelvic ligament, as well Discussion
as a higher vein ligation [21]. Care must be taken with
these procedures to recognize that there can be mul- After confirmed diagnosis, medical management is
tiple main trunks (instead of the usual single trunk) the most conservative effective therapy with the least
providing venous drainage from the ovary, 40% on amount of risk for patients with PCS. These therapies
the time on the left and 25% on the right [13]. One can include progestins, GnRH agonists, danazol, phle-
small cohort study reported efficacy with this treat- botonics, dihydroergotamine, and NSAIDs. However,
ment, with approximately 80% of women reporting these therapies can be ineffective in some patients or
total elimination of pain [21]. At 1 year, all of the side effects may prohibit and or limit their use. These
remaining study cohort (74% after dropout) reported patients should subsequently be offered surgical or
resolution of pain [21]. Though attractive, the nonsurgical procedural interventions. Transcatheter
reported procedure requires an experienced laparo- embolotherapy (TCE) is effective and low risk and
scopic surgeon with excellent knowledge of the anat- should be considered next line therapy; however, in
omy, as accessing the ovarian venous vasculature is patients who have suspected concomitant pelvic path-
performed at various locations along its course, not ology, surgical evaluation and treatment may be
restricted to the infundibulopelvic ligament where it a more effective option.
is most easily accessible.
From published series in the 1990s, success rates
Extirpative procedures such as hysterectomy with for reduction of chronic pelvic pain ranged from 50%
and without removal of one or both ovaries have to 80%; however, with advancements in technique,
shown to be effective as well. Some patients with significant relief is now reported in 60%–100% of
PCS have experienced marked pain relief with these patients [1]. This improvement may stem from mul-
therapies, with VAS scores decreasing from 10 to 0 tiple factors such as advancements in diagnostic
over 1 year following hysterectomy with BSO [22, 23]. imaging modalities, as well as innovations in surgical
In the same cohort, however, one in three women and radiological techniques. While these results are
reported residual pain [22] with a return of symptom- encouraging, the overarching data outcomes are
atology for some, 30%, at 1 year [13]. The confirm- contradictory. For example, 6%–31.8% of patients do
ation of PCS in these patients, however, was not well not get substantial relief following ovarian emboliza-
established, and in one trial 25% were shown to have tion [6]. We believe this discrepancy is due to
adenomyosis on postsurgical histology [22]. All in all, a number of reasons. First, pathophysiology is poorly
though hysterectomy appears beneficial, it is difficult understood, and symptoms can overlap with other
to recommend hysterectomy or hysterectomy with diseases, thereby leading to either incorrect and/or
BSO over other treatment modalities given the cur- underestimated diagnosis. Next, confirmatory diag-
rent data. nostic testing itself is quite variable, depending on
not only patient access to testing, but also variability
There is an important caveat to this conclusion. in these imaging results, reliant on both the testing
Although surgical therapies have less evidence to sup- operator and subsequent radiological interpretation.
port their efficacy and may put patients at higher risk Adding to diagnostic confusion is that ovarian dila-
when compared to interventional radiological tech- tion, though associated with and predictive of PCS, is
niques, surgical evaluation allows for the identifica- not itself synonymous with venous incompetence or
tion and treatment of concomitant pelvic pathologies symptoms [2]. So how next should one proceed?
such as endometriosis; and this is not trivial because
70% of patients with chronic pelvic pain have been 117

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