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Overview of the treatment of endometriosis

Author
Robert S Schenken, MD
Section Editor
Robert L Barbieri, MD
Deputy Editor
Kristen Eckler, MD, FACOG
Disclosures: Robert S Schenken, MD Nothing to disclose. Robert L Barbieri, MD Nothing to
disclose. Kristen Eckler, MD, FACOG Employee of UpToDate, Inc.
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found,
these are addressed by vetting through a multi-level review process, and through requirements
for references to be provided to support the content. Appropriately referenced content is required
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Conflict of interest policy
All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: Jan 2015. | This topic last updated: Jul 24, 2013.
INTRODUCTION According to the Practice Committee of the American Society for
Reproductive Medicine, endometriosis should be viewed as a chronic disease that requires a
life-long management plan with the goal of maximizing the use of medical treatment and
avoiding repeated surgical procedures [1]. Despite extensive research, the optimal management
of endometriosis is unclear. This topic will review medical and surgical options for treating
women with this disease. Clinical features and diagnosis of endometriosis, as well as
management of thoracic endometriosis, are discussed separately. (See "Pathogenesis, clinical
features, and diagnosis of endometriosis" and "Thoracic endometriosis".)
GENERAL APPROACH Clinical manifestations of endometriosis fall into three general
categories: pelvic pain, infertility, and pelvic mass. The goal of therapy is to relieve these
symptoms. There is no high quality evidence that one medical therapy is superior to another for
managing pelvic pain due to endometriosis, or that any type of medical treatment will affect
future fertility. Therefore, treatment decisions are individualized, taking into account the severity
of symptoms, the extent and location of disease, whether there is a desire for pregnancy, the age
of the patient, medication side effects, surgical complication rates, and cost.
Treatment options include:
Expectant management
Analgesia
Hormonal medical therapy

Estrogen-progestin oral contraceptives, cyclic or continuous


Gonadotropin-releasing hormone (GnRH) agonists
Progestins, given by an oral, parenteral, or intrauterine route
Danazol
Aromatase inhibitors
Surgical intervention, which may be conservative (retain uterus and ovarian tissue) or definitive
(removal of the uterus and possibly the ovaries)
Combination therapy in which medical therapy is given before and/or after surgery
Laparoscopy is the gold standard for establishing the diagnosis of endometriosis, and provides an
opportunity for conservative surgical treatment. Therapeutic intervention is desirable at the time
of diagnosis to ablate or excise implants and adhesions, thus potentially preventing or delaying
disease or symptom progression. Early surgical therapy also avoids the expense and side effects
of medical therapy. Potential disadvantages include inadvertent damage to adjacent organs
(especially the bowel and bladder), postoperative infectious complications, and mechanical
trauma to pelvic structures that may result in greater adhesion formation (see "Surgical
management of pelvic pain due to endometriosis", section on 'Conservative versus definitive
surgery').
After the initial diagnostic procedure, expectant management is considered primarily for two
groups of patients: women with no or minimal symptoms and perimenopausal women. Although
relief of symptoms is not as important for asymptomatic or minimally symptomatic women,
these patients may benefit from therapy to retard progression of the disease because studies
suggest that endometriosis is a progressive disease in most women [2]. While most studies
suggest that oral estrogen-progestin contraceptives reduce the incidence of endometriosis, some
suggest no effect or a slight increase [3-5].
After menopause, endometriotic implant growth is suppressed as a result of markedly reduced
ovarian estrogen production. Therefore, perimenopausal women with tolerable symptoms may
opt for expectant management until menopause to avoid the side effects and cost of treatment.
Alternatively, analgesia with nonsteroidal antiinflammatory drugs (NSAIDs) may provide
acceptable results over the short-term. Young women with significant symptoms generally
require more aggressive medical or surgical therapy.
TREATMENT OF PELVIC PAIN Women with pelvic pain and suspected endometriosis may
be managed with empiric medical therapy prior to establishing a definitive diagnosis by
laparoscopy [6,7]. We generally suggest analgesics and/or combined oral estrogen-progestin
contraceptives for women with no more than mild pelvic pain and a GnRH agonist for those with
moderate to severe pelvic pain. The advantages and disadvantages of medical therapy of pelvic
pain in women with endometriosis are listed in the table (table 1). Although 80 to 90 percent of

patients will have some improvement in symptoms with medical therapy, medical interventions
neither enhance fertility nor diminish endometriomas or adhesions [8-10]. Therefore, women
with suspected endometriomas and advanced stages of disease, or infertility, are more
appropriately managed surgically.
Initial approach
Analgesics There are no large randomized trials evaluating the use of any analgesic for
treatment of pain in women with endometriosis. In observational studies, the efficacy of
analgesics was limited to pain that was no more than minimal [8]. Although NSAIDs are
commonly used for analgesia, there are no high quality data showing that they are effective for
managing pain due to endometriosis or more effective than other agents [11]. Use of NSAIDs is
based on their ready availability, low cost, acceptable side effect profile, and evidence from
randomized clinical trials consistently demonstrating that they are effective treatment of primary
dysmenorrhea. (See "Treatment of primary dysmenorrhea in adult women".)
Estrogen-progestin oral contraceptives Estrogen-progestin oral contraceptives (OCs) are a
good choice for women with minimal or mild pain who also want to prevent pregnancy. An
advantage of OCs over most other hormonal interventions is that they can be taken indefinitely.
A placebo-controlled randomized trial demonstrated that use of OCs is effective for relief of
dysmenorrhea [12]. OCs may also retard progression of disease, but evidence is conflicting [35,12-17]. The purported therapeutic mechanism is decidualization and subsequent atrophy of
endometrial tissue, including ectopic endometrial tissue.
Cyclic OCs may not be as effective as GnRH agonists. The only randomized trial that directly
compared a low-dose cyclic OC to a GnRH agonist (goserelin) reported that both drugs provided
significant relief of pain, but goserelin was superior for treatment of dyspareunia [18,19]. Data
on the comparative efficacy of continuous OCs are inconsistent:
A randomized trial including 133 women with relapse of endometriosis-associated pain
compared treatment with a GnRH agonist plus add-back therapy, a GnRH agonist alone, and
continuous monophasic OCs for 12 months [20]. Patients treated with a GnRH agonist had
significantly greater reduction in pelvic pain, dysmenorrhea, and dyspareunia than patients
treated with continuous OCs. The group taking a GnRH agonist plus add-back therapy had the
highest quality of life scores.
In contrast, a randomized trial including 47 women with endometriosis-associated pelvic pain
that directly compared use of continuous monophasic OCs to a GnRH agonist (leuprolide with
add-back) for 48 weeks found the regimens were equally effective in reduction of pain [21].
Both trials were well-designed, but the second study was limited by the small number of patients
and high drop-out rate (40 percent).
Thus, it is unclear whether a cyclic, continuous, or tricycle regimen is most effective [8]. If pain
does not respond well to cyclic therapy, switching to continuous OC administration may be

effective [22]. A monophasic pill is adequate; there is no evidence that a triphasic pill has any
advantages for treatment of endometriosis-related pain. The clinical regimen for continuous or
extended use of OCs is described separately. (See "Hormonal contraception for suppression of
menstruation", section on 'Extended and continuous use of contraceptive pills'.)
Nonoral estrogen-progestin contraceptives (ring, patch) may also be effective, but have not been
studied extensively [23].
Failure of initial medical therapy We offer hormonal interventions other than OCs to women
with early stage disease who are not achieving adequate pain relief after a three- to six-month
trial with analgesics or OCs and to those with recurrent mild endometriosis and pain. The
rationale for use of hormonal intervention is that altering the patient's estrogen/progesterone
profile should affect the course of the disease since ovarian steroids affect the growth of
endometriosis. This hypothesis is supported by the observation that pregnancy and menopause,
physiologic states which cause alterations in ovarian hormone concentrations, appear to be
associated with a reduction in pelvic pain.
The three hormonal interventions (other than OCs) most commonly used to treat endometriosis
are gonadotropin-releasing hormone (GnRH) agonist analogs, danazol, and progestins. GnRH
analogs and danazol induce a state of "pseudomenopause," whereas progestins alone or in
combination with estrogen hormonally mimic pregnancy.
GnRH agonists We suggest use of a GnRH agonist for treatment of moderate to severe pain
associated with endometriosis. Randomized trials have shown that GnRH agonists are more
effective than placebo and as effective as other medical therapies for relieving pain and reducing
the size of endometriotic implants [24]. With add-back therapy, side effects are often better
tolerated than those associated with a progestin or danazol. Similar to other medical treatments,
GnRH agonists do not enhance fertility [10].
GnRH agonists can be administered by daily nasal spray, or intramuscular injections every one to
three months. Generally, initial treatment with a GnRH agonist is continued for six months. A
randomized trial showed that an empiric trial of GnRH agonist therapy, without
surgical/histological confirmation of disease, is reasonable in patients with dysmenorrhea or
chronic pelvic pain who have not responded to NSAIDs or OCs, and in whom other causes of
chronic pelvic pain have been excluded by history, physical examination, and laboratory testing
[25]. Baseline tests, such as a complete blood count with differential and erythrocyte
sedimentation rate, urinalysis, and testing for chlamydia and gonorrhea infection, are obtained to
screen for a chronic infectious or inflammatory process. Pelvic ultrasound is highly sensitive for
identifying pelvic masses and determining the origin of the mass (ovary, uterus, fallopian tube).
(See "Evaluation of chronic pelvic pain in women".)
A detailed discussion of the use and efficacy of GnRH agonists for treatment of endometriosis
can be found separately. (See "Gonadotropin releasing hormone agonists for long-term treatment
of endometriosis".)

Progestins Progestins inhibit endometriotic tissue growth by causing decidualization initially,


and then atrophy. They also inhibit pituitary gonadotropin secretion and ovarian hormone
production.
In randomized trials and prospective observational studies, progestins alone, at appropriate
doses, were an effective treatment of pelvic pain caused by endometriosis: over 80 percent of
women had partial or complete pain relief with this therapy [26-30]. The effectiveness of
progestins was best illustrated in a multicenter randomized trial including 274 women with
surgically diagnosed endometriosis who were treated with intramuscular injections of DMPA-SC
(104 mg) or leuprolide (11.25 mg) over a six-month interval [29]. Use of DMPA was associated
with a significant reduction in dysmenorrhea, dyspareunia, pelvic pain, pelvic tenderness, and
pelvic induration at 12 months follow-up, and these effects were comparable to those achieved
with the GnRH agonist.
The effectiveness of progestins in eliminating implants and the risk of recurrent endometriosis
following treatment is less well-documented. A few studies have reported significantly reduced
implant scores (determined at laparoscopy) after progestin therapy [27,31].
There is no evidence that high-dose oral progestin treatment is associated with the bone loss
observed with GnRH agonists. Indeed, 5 mg/day of norethindrone add-back has been shown to
diminish the bone loss associated with GnRH agonist therapy. Progestins also do not have as
detrimental an impact on lipids as danazol. In addition, high-dose progestin regimens are
typically less expensive than regimens containing a GnRH agonist. However, many women do
not tolerate high dose progestin treatment because of weight gain, irregular uterine
bleeding/spotting, and mood changes (eg, depression). For these reasons, we feel GnRH agonists
remain the first-line treatment choice, but progestin-only treatment is a reasonable second line
treatment [32].
There are several options for progestin therapy. The choice depends upon the contraceptive needs
of the patient, side-effect profile of the various drugs, and patient preference.
Oral medroxyprogesterone acetate (MPA) (10 mg three times a day, maximum total dose 100
mg daily) or norethindrone acetate (5 mg daily and increased by 2.5 mg every two weeks if pain
persists, maximum total dose 15 mg daily; however, most patients become amenorrheic at daily
doses of 5 to 10 mg). Treatment is continued for six-months [26,27].
Depot medroxyprogesterone acetate (DMPA) is given as an injection (104 to 150 mg every
three months). This therapy has been as effective as leuprolide and danazol in randomized trials
[29,33,34]. Side effects include irregular menstrual bleeding, nausea, breast tenderness, fluid
retention, and depression. However, prolonged use may result in loss of bone mineral density.
(See "Depot medroxyprogesterone acetate for contraception".)
Use of the levonorgestrel-releasing intrauterine device (LNG-IUD) after postoperative
treatment of endometriosis has been evaluated in several small randomized trials [35-40]. At
approximately one-year follow-up, most trials found that the LNG-IUD resulted in a significant
improvement compared with pretreatment testing or expectant management in measures of

chronic pelvic pain and dysmenorrhea, but not of dyspareunia. The LNG-IUD was equally or
less effective than GnRH agonists in preventing recurrence of chronic pelvic pain or
dysmenorrhea following surgery [38,39]. Irregular menstrual bleeding and amenorrhea are
common side effects, but in contrast to depot medroxyprogesterone acetate, bone density is
preserved [36]. Each LNG-IUD has sufficient LNG to be effective for five years. After five years
of use, the device should be removed, but can be replaced with a new device if appropriate. The
LNG-IUD has few systemic side effects compared to other hormonal methods.
A small observational study and a randomized trial reported that the etonogestrel subdermal
implant (Implanon) was effective for decreasing the intensity of endometriosis-related pain
(dyspareunia, dysmenorrhea, nonmenstrual pelvic pain) [41,42]. The therapeutic effect and sideeffect profile were comparable to DMPA [41]. Pain was reduced by at least 50 percent after six
months of use and maintained for 12 months.
A randomized trial including 253 women compared the efficacy and safety of dienogest against
leuprolide acetate for treatment of pain associated with endometriosis [43]. Dienogest 2 mg/day
orally was equivalent in efficacy to leuprolide at standard dose in relieving the pain associated
with endometriosis, but was associated with fewer hypoestrogenic effects (flushes, reduction in
bone mineral density) and more unscheduled bleeding.
Duration of therapy Most clinical trials of progestin therapy have been limited to 6 or 12
months duration for practical reasons. Based on clinical experience in patients with
endometriosis and other disorders, progestin therapy can be extended indefinitely, if effective
and well-tolerated. Bone loss is a concern with long-term administration of DMPA or high dose
oral MPA, especially in women with risk factors for osteoporosis, but bone density generally
improves if the woman returns to normal ovulatory function and estrogen production. (See
"Drugs that affect bone metabolism", section on 'Medroxyprogesterone acetate' and "Depot
medroxyprogesterone acetate for contraception", section on 'Reduction in bone mineral density'.)
Long-term use of norethindrone acetate can lead to a significant reduction in HDL cholesterol
and significant increases in LDL cholesterol and triglycerides [44]. Given these risks, bone
mineral density and lipid levels may be monitored, as appropriate, in patients on long-term
therapy.
Long-term use of the LNG-IUD or the etonogestrel implant does not significantly affect bone
mineral density or lipid levels.
Progesterone antagonists Progesterone antagonists and selective progesterone receptor
modulators have also been used successfully in pilot studies of treatment of endometriosis [45].
Use of these agents led to a reduction of both nonmenstrual pelvic pain and dysmenorrhea. An
advantage of these agents is that they suppress growth of endometrial cells without suppressing
estrogen's effects on other tissues. However, chronic use of progesterone antagonists appears to
create histological changes in the endometrium (cystic glandular dilatation) that resemble
endometrial hyperplasia [46]. The clinical significance of these changes requires further
investigation. (See "Therapeutic use and adverse effects of progesterone receptor antagonists and
selective progesterone receptor modulators", section on 'Endometriosis'.)

Danazol Danazol is effective in resolving implants when treating mild or moderate stages of
disease and over 80 percent of patients experience relief or improvement of pain symptoms
within two months of treatment [27,47,48]. A randomized trial that compared pain sources in
women treated with danazol or placebo reported a significant decrease in the level of pelvic pain,
lower back pain, defecation pain, and total pain in those treated with danazol [27]. The
improvement in pain scores was still present six months after discontinuation of danazol therapy.
Danazol is a 19-nortestosterone derivative with progestin-like effects. Its mechanisms of action
include inhibition of pituitary gonadotropin secretion, direct inhibition of endometriotic implant
growth, and direct inhibition of ovarian enzymes responsible for estrogen production. Danazol is
given orally in divided doses ranging from 400 to 800 mg daily, generally for six months.
Most women taking danazol have side effects that can be dose-dependent, and a small percentage
of patients discontinue the drug because of them. Side effects include weight gain, muscle
cramps, decreased breast size, acne, hirsutism, oily skin, decreased high density lipoprotein
levels, increased liver enzymes, hot flashes, mood changes, and depression. Androgenic side
effects associated with use of danazol are not treatable except by lowering the dose. By
comparison, the hypoestrogenic symptoms produced by GnRH agonists can be minimized by
add-back therapy.
Aromatase inhibitors Traditional hormonal interventions for endometriosis have targeted
ovarian estrogen production or antagonized estrogen action. Although not approved for the
treatment of pelvic pain caused by endometriosis, use of aromatase inhibitors is a novel,
promising approach [49]. These agents appear to regulate local estrogen formation within the
endometriotic lesions themselves, in addition to inhibiting estrogen production in the ovary,
brain, and periphery (eg, adipose tissue) [49]. In endometriotic tissue, prostaglandin E2
stimulates both aromatase overexpression and activity, which results in local production of
estrogens from androgens. Estrogen, in turn, induces further prostaglandin E2 formation, thereby
establishing a positive feedback cycle within the lesion [50].
In multiple case reports and small series and a randomized trial, aromatase inhibitors have been
used (off-label) to interrupt this pathway in the treatment of severe endometriosis [51-58]. A
systematic review of these studies concluded aromatase inhibitors significantly reduced pain
compared with GnRH agonists alone [59].
Patients may respond differently to different aromatase inhibitors [60]. The two most widely
used agents are anastrozole (1 mg) or letrozole (2.5 mg) daily.
It is important to remember that aromatase inhibitors cause significant bone loss with prolonged
use and cannot be used as single agents in premenopausal women because they stimulate FSH
release and cause multi-follicular cyst development. If these agents are used to treat pain caused
by endometriosis in this population, they should be prescribed in combination with a GnRH
agonist or an oral estrogen-progestin contraceptive [55] to suppress follicular development.
For patients in whom use of a GnRH agonist or oral estrogen-progestin contraceptive is not
possible, norethindrone acetate (5 mg) is another option. In fact, the combination of letrozole and

norethisterone acetate was more effective in reducing pain and deep dyspareunia in women with
rectovaginal endometriosis than norethisterone acetate alone, but letrozole was associated with a
high incidence of adverse effects, cost more, and did not improve patient satisfaction or reduce
recurrence of pain [61].
Acupuncture A systematic review of treatment of pain associated with endometriosis with
acupuncture found only one randomized trial that met inclusion criteria [62]. In that trial (n =
67), auricular acupuncture was significantly more effective than Chinese herbal medicine for
treating dysmenorrhea in women with endometriosis [63].
Diet There are no dietary guidelines for prevention or treatment of endometriosis. One study
reported that a lower risk of developing endometriosis was associated with a high intake of green
vegetables and fruit and an increased risk with intake of beef or other red meat or ham [64].
There was no alteration of risk of endometriosis with consumption of other food items tested,
including alcohol, coffee, fish and milk. Several studies have addressed diet and dysmenorrhea,
but not exclusively in patients with endometriosis. (See "Treatment of primary dysmenorrhea in
adult women", section on 'Diet and vitamins'.)
Surgical management Surgery may be indicated for management of endometriosis that cannot
be treated with medical therapy or to provide a definitive diagnosis. Surgical management of
endometriosis is discussed in detail separately. (See "Surgical management of pelvic pain due to
endometriosis".)
Preoperative and postoperative medical therapy
Preoperative and postoperative medical therapy is discussed in detail separately. (See "Surgical
management of pelvic pain due to endometriosis", section on 'Postoperative medical therapy' and
"Surgical management of pelvic pain due to endometriosis", section on 'Preoperative medical
suppressive therapy'.)
TREATMENT OF INFERTILITY Although endometriosis can reduce fecundability (ie, the
probability of conceiving during a monthly cycle), it does not usually completely prevent
conception. The mechanism for impaired fertility may involve anatomic distortion from pelvic
adhesions and endometriomas and/or production of substances (eg, prostanoids, cytokines,
growth factors) which are "hostile" to normal ovarian function/ovulation, fertilization, and
implantation [65].
The treatment of infertility associated with endometriosis involves a combination of expectant
management, surgery, and assisted reproduction techniques. Treatment with hormonal
suppression is ineffective [66]. A stepwise approach to treatment of infertility in women with
endometriosis can be found separately (see "Pathogenesis and treatment of infertility in women
with endometriosis").
TREATMENT OF PELVIC MASS An endometrioma may be associated with symptoms of
endometriosis or identified at the time of evaluation for a pelvic mass. Medical therapy is
unlikely to result in complete regression of large endometriomas and precludes a definitive

histologic diagnosis; therefore, surgery is the preferred therapeutic approach. Asymptomatic


endometriomas are often removed to confirm the diagnosis, exclude malignancy, and prevent
complications, such as rupture or torsion requiring emergency surgery. However, ovarian reserve
can be diminished following surgical excision [67].
Management of ovarian endometriomas is discussed in more detail separately. (See "Diagnosis
and management of ovarian endometriomas".)
TREATMENT OF SYMPTOMS RELATED TO DEEP ENDOMETRIOSIS Deep infiltrating
endometriosis is a term used to describe infiltrative forms of the disease that involve the
uterosacral ligaments, rectovaginal septum, bowel, ureters, or bladder. The origin is probably
intraperitoneal endometriotic implants that have invaded and caused inflammation of the
involved tissue. Another potential etiology is growth of retroperitoneal mllerian remnants.
Asymptomatic disease is managed expectantly [68]. Medical therapy is appropriate for women
with bothersome symptoms, except those with obstructive uropathy or symptomatic bowel
stenosis. Although medical therapy of symptomatic disease has generally been reported to be
ineffective or transiently effective, with recurrence rates approaching 70 percent [69],
endometriosis is a chronic disease and cessation of medical therapy may account for the high
frequency of symptom recurrence. A review of studies of various hormonal treatments of
rectovaginal endometriosis found that most patients receiving medical therapy for 6 to 12 months
reported a significant reduction in dysmenorrhea and painful intercourse and defecation during
treatment, but recurrence rates were high when medical therapy was discontinued [70].
Either a continuous estrogenprogestin combination or low-dose norethindrone can be used. In
women with rectovaginal or colorectal endometriosis, continuous norethisterone acetate therapy
(2.5 mg/day) for 12 months has been reported to improve pelvic pain, dyspareunia, dyschezia,
diarrhea, and intestinal cramping, but did not have a significant effect on constipation, feeling of
incomplete evacuation, and abdominal bloating [71,72].
Surgical therapy is effective for relieving pelvic pain, dyspareunia, painful defecation, and lower
urinary tract symptoms [73,74]; however, recurrence rates of 30 and 43 percent at four and eight
years follow-up, respectively, have been reported [75]. Medical treatment rather than repeat
surgery may be useful in women with persistent symptoms [72]. Surgical resection does not
enhance future pregnancy rates [76].
There is no consensus on the extent of resection necessary to treat deep endometriosis. Extensive
dissection in the rectovaginal septum and rectal wall dissection are often necessary and require
the skill of an experienced surgeon. Performing hysterectomy and bilateral salpingoophorectomy
alone is inadequate definitive therapy if endometriosis involving the bowel is left untreated. In
these cases, bowel resection may be necessary [77,78].
In women with endometriotic lesions infiltrating the bladder muscularis propria, partial
cystectomy has been reported to result in long-term relief of symptoms [74].

Surgery for deep endometriosis is associated with a relatively high risk of postoperative
complications, such as de-novo or worsening voiding dysfunction, rectal dysfunction, and
rectovaginal fistula [78-82].
TREATMENT OF LESIONS OF NON-REPRODUCTIVE ORGANS Ovarian suppression
with GnRH agonists is probably the optimum initial therapy for symptomatic extra-pelvic
endometriosis [83]. However, obstruction of the ureter or bowel should be treated surgically.
(See "Thoracic endometriosis".)
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education pieces are longer, more sophisticated, and more detailed. These articles are written at
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Here are the patient education articles that are relevant to this topic. We encourage you to print or
e-mail these topics to your patients. (You can also locate patient education articles on a variety of
subjects by searching on patient info and the keyword(s) of interest.)
Basics topics (see "Patient information: Endometriosis (The Basics)")
Beyond the Basics topics (see "Patient information: Endometriosis (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
The goal of therapy is to relieve symptoms of endometriosis: pelvic pain, infertility, and pelvic
mass. There is no high quality evidence showing that one medical therapy is more effective than
another for treatment of pelvic pain due to endometriosis. There is also no high quality evidence
that medical or surgical intervention will affect future fertility. Therefore, individual treatment
decisions are based upon the severity of symptoms, the extent and location of disease, whether
there is a desire for pregnancy, the age of the patient, medication side effects, surgical
complication rates, and cost. (See 'General approach' above.)
An initial diagnostic laparoscopy for establishing the presence of endometriosis provides an
opportunity for ablation or excision of implants and adhesions, thus potentially preventing or
delaying disease or symptom progression. This approach should be considered in patients with
suspected advanced stages of disease (ie, endometriomas) and may benefit women with
endometriosis-associated infertility. Early surgical therapy also avoids the expense and side
effects of medical therapy. (See 'General approach' above.)
Empiric medical therapy with nonsteroidal anti-inflammatory drugs, oral contraceptives, or
GnRH agonists may be used in women with pelvic pain and suspected endometriosis, prior to
establishing the diagnosis surgically. This may provide sufficient pain relief and avoid a

laparoscopy. There is insufficient long-term follow-up of patients managed initially with medical
therapy to assess symptom recurrence or the eventual need for surgical intervention.
Treatment of pain
For women with no more than mild pelvic pain, we suggest nonsteroidal antiinflammatory
drugs over other medical interventions (Grade 2B). For women who also desire contraception,
we suggest oral contraceptives (Grade 2C). (See 'Initial approach' above.)
For women with moderate pain who are not achieving adequate pain relief with nonsteroidal
antiinflammatory drugs and/or combined oral contraceptives, and those with recurrent mild
endometriosis and pain, we suggest treatment with a GnRH agonist over other hormonal
therapies (Grade 2B). (See 'GnRH agonists' above.) Use of GnRH agonists avoids the
bothersome side effects of progestins (weight gain, irregular uterine bleeding, mood changes)
and danazol (weight gain, muscle cramps, decreased breast size, acne, hirsutism, oily skin, mood
changes).
For women who want to avoid the high cost and risk of bone loss associated with GnRH
agonists, we suggest treatment with a progestin (Grade 2B). Progestins have a more favorable
side effect profile than danazol. (See 'Progestins' above and 'Danazol' above.)
For women with symptoms that are severe, incapacitating, or acute (rupture or torsion of an
endometrioma), or who have advanced disease (eg, anatomic distortion of the pelvic organs,
endometriotic cysts, or obstruction of the bowel or urinary tract), we suggest surgical rather than
medical therapy (Grade 2C). We also suggest surgical intervention for women whose symptoms
have failed to resolve or have worsened under medical management (Grade 2C). (See 'Surgical
management' above.)
Treatment of infertility
The treatment of infertility associated with endometriosis involves a combination of expectant
management, surgery, and assisted reproduction techniques. Drug treatment is ineffective. (See
'Treatment of infertility' above.)
Treatment of pelvic mass
Medical therapy is unlikely to result in complete regression of large endometriomas and
precludes a definitive histologic diagnosis. Therefore, surgery is the preferred therapeutic
approach. (See 'Treatment of pelvic mass' above.)
Treatment of deep endometriosis
For women with pelvic pain, dyspareunia, or painful defecation related to deep endometriosis,
we suggest surgical rather than medical therapy (Grade 2C).
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REFERENCES
1. Practice Committee of American Society for Reproductive Medicine. Treatment of pelvic
pain associated with endometriosis. Fertil Steril 2008; 90:S260.
2. Mahmood TA, Templeton A. The impact of treatment on the natural history of
endometriosis. Hum Reprod 1990; 5:965.
3. Vessey MP, Villard-Mackintosh L, Painter R. Epidemiology of endometriosis in women
attending family planning clinics. BMJ 1993; 306:182.
4. Moen MH. Is a long period without childbirth a risk factor for developing endometriosis?
Hum Reprod 1991; 6:1404.
5. Parazzini F, La Vecchia C, Franceschi S, et al. Risk factors for endometrioid, mucinous
and serous benign ovarian cysts. Int J Epidemiol 1989; 18:108.
6. American College of Obstetricians and Gynecologists. ACOG Committee Opinion.
Number 310, April 2005. Endometriosis in adolescents. Obstet Gynecol 2005; 105:921.
7. ACOG Committee on Practice Bulletins--Gynecology. ACOG practice bulletin. Medical
management of endometriosis. Number 11, December 1999 (replaces Technical Bulletin
Number 184, September 1993). Clinical management guidelines for obstetriciangynecologists. Int J Gynaecol Obstet 2000; 71:183.
8. Kennedy S, Bergqvist A, Chapron C, et al. ESHRE guideline for the diagnosis and
treatment of endometriosis. Hum Reprod 2005; 20:2698.
9. American College of Obstetricians and Gynecologists. Medical management of
endometriosis. ACOG practice bulletin 11, American College of Obstetricians and
Gynecologists, Washington, DC 1999.
10. Hughes E, Brown J, Collins JJ, et al. Ovulation suppression for endometriosis. Cochrane
Database Syst Rev 2007; :CD000155.
11. Allen C, Hopewell S, Prentice A, Gregory D. Nonsteroidal anti-inflammatory drugs for
pain in women with endometriosis. Cochrane Database Syst Rev 2009; :CD004753.
12. Harada T, Momoeda M, Taketani Y, et al. Low-dose oral contraceptive pill for
dysmenorrhea associated with endometriosis: a placebo-controlled, double-blind,
randomized trial. Fertil Steril 2008; 90:1583.
13. Buttram VC Jr. Cyclic use of combination oral contraceptives and the severity of
endometriosis. Fertil Steril 1979; 31:347.

14. Strathy JH, Molgaard CA, Coulam CB, Melton LJ 3rd. Endometriosis and infertility: a
laparoscopic study of endometriosis among fertile and infertile women. Fertil Steril 1982;
38:667.
15. Kirshon B, Poindexter AN 3rd. Contraception: a risk factor for endometriosis. Obstet
Gynecol 1988; 71:829.
16. Mahmood TA, Templeton A. Prevalence and genesis of endometriosis. Hum Reprod
1991; 6:544.
17. Moen MH. Endometriosis in women at interval sterilization. Acta Obstet Gynecol Scand
1987; 66:451.
18. Vercellini P, Trespidi L, Colombo A, et al. A gonadotropin-releasing hormone agonist
versus a low-dose oral contraceptive for pelvic pain associated with endometriosis. Fertil
Steril 1993; 60:75.
19. Davis L, Kennedy SS, Moore J, Prentice A. Modern combined oral contraceptives for
pain associated with endometriosis. Cochrane Database Syst Rev 2007; :CD001019.
20. Zupi E, Marconi D, Sbracia M, et al. Add-back therapy in the treatment of endometriosisassociated pain. Fertil Steril 2004; 82:1303.
21. Guzick DS, Huang LS, Broadman BA, et al. Randomized trial of leuprolide versus
continuous oral contraceptives in the treatment of endometriosis-associated pelvic pain.
Fertil Steril 2011; 95:1568.
22. Vercellini P, Frontino G, De Giorgi O, et al. Continuous use of an oral contraceptive for
endometriosis-associated recurrent dysmenorrhea that does not respond to a cyclic pill
regimen. Fertil Steril 2003; 80:560.
23. Vercellini P, Barbara G, Somigliana E, et al. Comparison of contraceptive ring and patch
for the treatment of symptomatic endometriosis. Fertil Steril 2010; 93:2150.
24. Brown J, Pan A, Hart RJ. Gonadotrophin-releasing hormone analogues for pain
associated with endometriosis. Cochrane Database Syst Rev 2010; :CD008475.
25. Ling FW. Randomized controlled trial of depot leuprolide in patients with chronic pelvic
pain and clinically suspected endometriosis. Pelvic Pain Study Group. Obstet Gynecol
1999; 93:51.
26. Luciano AA, Turksoy RN, Carleo J. Evaluation of oral medroxyprogesterone acetate in
the treatment of endometriosis. Obstet Gynecol 1988; 72:323.

27. Telimaa S, Puolakka J, Rnnberg L, Kauppila A. Placebo-controlled comparison of


danazol and high-dose medroxyprogesterone acetate in the treatment of endometriosis.
Gynecol Endocrinol 1987; 1:13.
28. Prentice A, Deary AJ, Bland E. Progestagens and anti-progestagens for pain associated
with endometriosis. Cochrane Database Syst Rev 2000; :CD002122.
29. Crosignani PG, Luciano A, Ray A, Bergqvist A. Subcutaneous depot
medroxyprogesterone acetate versus leuprolide acetate in the treatment of endometriosisassociated pain. Hum Reprod 2006; 21:248.
30. Vercellini P, Cortesi I, Crosignani PG. Progestins for symptomatic endometriosis: a
critical analysis of the evidence. Fertil Steril 1997; 68:393.
31. Dawood MY, Obasiolu CW, Ramos J, Khan-Dawood FS. Clinical, endocrine, and
metabolic effects of two doses of gestrinone in treatment of pelvic endometriosis. Am J
Obstet Gynecol 1997; 176:387.
32. Regidor PA, Regidor M, Schmidt M, et al. Prospective randomized study comparing the
GnRH-agonist leuprorelin acetate and the gestagen lynestrenol in the treatment of severe
endometriosis. Gynecol Endocrinol 2001; 15:202.
33. Schlaff WD, Carson SA, Luciano A, et al. Subcutaneous injection of depot
medroxyprogesterone acetate compared with leuprolide acetate in the treatment of
endometriosis-associated pain. Fertil Steril 2006; 85:314.
34. Vercellini P, De Giorgi O, Oldani S, et al. Depot medroxyprogesterone acetate versus an
oral contraceptive combined with very-low-dose danazol for long-term treatment of
pelvic pain associated with endometriosis. Am J Obstet Gynecol 1996; 175:396.
35. Abou-Setta AM, Al-Inany HG, Farquhar CM. Levonorgestrel-releasing intrauterine
device (LNG-IUD) for symptomatic endometriosis following surgery. Cochrane Database
Syst Rev 2006; :CD005072.
36. Wong AY, Tang LC, Chin RK. Levonorgestrel-releasing intrauterine system (Mirena) and
Depot medroxyprogesterone acetate (Depoprovera) as long-term maintenance therapy for
patients with moderate and severe endometriosis: a randomised controlled trial. Aust N Z
J Obstet Gynaecol 2010; 50:273.
37. Vercellini P, Frontino G, De Giorgi O, et al. Comparison of a levonorgestrel-releasing
intrauterine device versus expectant management after conservative surgery for
symptomatic endometriosis: a pilot study. Fertil Steril 2003; 80:305.
38. Petta CA, Ferriani RA, Abrao MS, et al. Randomized clinical trial of a levonorgestrelreleasing intrauterine system and a depot GnRH analogue for the treatment of chronic
pelvic pain in women with endometriosis. Hum Reprod 2005; 20:1993.

39. Bayoglu Tekin Y, Dilbaz B, Altinbas SK, Dilbaz S. Postoperative medical treatment of
chronic pelvic pain related to severe endometriosis: levonorgestrel-releasing intrauterine
system versus gonadotropin-releasing hormone analogue. Fertil Steril 2011; 95:492.
40. Tanmahasamut P, Rattanachaiyanont M, Angsuwathana S, et al. Postoperative
levonorgestrel-releasing intrauterine system for pelvic endometriosis-related pain: A
randomized trial. Obstet Gynecol 2012.
41. Walch K, Unfried G, Huber J, et al. Implanon versus medroxyprogesterone acetate:
effects on pain scores in patients with symptomatic endometriosis--a pilot study.
Contraception 2009; 79:29.
42. Yisa SB, Okenwa AA, Husemeyer RP. Treatment of pelvic endometriosis with
etonogestrel subdermal implant (Implanon). J Fam Plann Reprod Health Care 2005;
31:67.
43. Strowitzki T, Marr J, Gerlinger C, et al. Dienogest is as effective as leuprolide acetate in
treating the painful symptoms of endometriosis: a 24-week, randomized, multicentre,
open-label trial. Hum Reprod 2010; 25:633.
44. Cirkel, U, Schweppe, KW, Ochs, H, et al. Effects of LHRH agonist therapy in the
treatment of endometriosis. In: Gonadotropin down-regulation in gynecological practice.
Vol 225, Chadha, DR, Willemsen, WNP (Eds). Aln R Liss, New York 1986. p. 189.
45. Chwalisz K, Perez MC, Demanno D, et al. Selective progesterone receptor modulator
development and use in the treatment of leiomyomata and endometriosis. Endocr Rev
2005; 26:423.
46. Spitz IM. Clinical utility of progesterone receptor modulators and their effect on the
endometrium. Curr Opin Obstet Gynecol 2009; 21:318.
47. Barbieri RL, Evans S, Kistner RW. Danazol in the treatment of endometriosis: analysis of
100 cases with a 4-year follow-up. Fertil Steril 1982; 37:737.
48. Selak V, Farquhar C, Prentice A, Singla A. Danazol for pelvic pain associated with
endometriosis. Cochrane Database Syst Rev 2007; :CD000068.
49. Attar E, Bulun SE. Aromatase inhibitors: the next generation of therapeutics for
endometriosis? Fertil Steril 2006; 85:1307.
50. Bulun SE, Zeitoun K, Takayama K, et al. Estrogen production in endometriosis and use
of aromatase inhibitors to treat endometriosis. Endocr Relat Cancer 1999; 6:293.
51. Razzi S, Fava A, Sartini A, et al. Treatment of severe recurrent endometriosis with an
aromatase inhibitor in a young ovariectomised woman. BJOG 2004; 111:182.

52. Takayama K, Zeitoun K, Gunby RT, et al. Treatment of severe postmenopausal


endometriosis with an aromatase inhibitor. Fertil Steril 1998; 69:709.
53. Ailawadi RK, Jobanputra S, Kataria M, et al. Treatment of endometriosis and chronic
pelvic pain with letrozole and norethindrone acetate: a pilot study. Fertil Steril 2004;
81:290.
54. Shippen ER, West WJ Jr. Successful treatment of severe endometriosis in two
premenopausal women with an aromatase inhibitor. Fertil Steril 2004; 81:1395.
55. Amsterdam LL, Gentry W, Jobanputra S, et al. Anastrazole and oral contraceptives: a
novel treatment for endometriosis. Fertil Steril 2005; 84:300.
56. Hefler LA, Grimm C, van Trotsenburg M, Nagele F. Role of the vaginally administered
aromatase inhibitor anastrozole in women with rectovaginal endometriosis: a pilot study.
Fertil Steril 2005; 84:1033.
57. Fatemi HM, Al-Turki HA, Papanikolaou EG, et al. Successful treatment of an aggressive
recurrent post-menopausal endometriosis with an aromatase inhibitor. Reprod Biomed
Online 2005; 11:455.
58. Soysal S, Soysal ME, Ozer S, et al. The effects of post-surgical administration of
goserelin plus anastrozole compared to goserelin alone in patients with severe
endometriosis: a prospective randomized trial. Hum Reprod 2004; 19:160.
59. Nawathe A, Patwardhan S, Yates D, et al. Systematic review of the effects of aromatase
inhibitors on pain associated with endometriosis. BJOG 2008; 115:818.
60. Mousa NA, Bedaiwy MA, Casper RF. Aromatase inhibitors in the treatment of severe
endometriosis. Obstet Gynecol 2007; 109:1421.
61. Ferrero S, Camerini G, Seracchioli R, et al. Letrozole combined with norethisterone
acetate compared with norethisterone acetate alone in the treatment of pain symptoms
caused by endometriosis. Hum Reprod 2009; 24:3033.
62. Zhu X, Hamilton KD, McNicol ED. Acupuncture for pain in endometriosis. Cochrane
Database Syst Rev 2011; :CD007864.
63. Xiang D, Situ Y, Liang X, et al. Ear acupuncture therapy for 37 cases of dysmenorrhea
due to endometriosis. J Tradit Chin Med 2002; 22:282.
64. Parazzini F, Chiaffarino F, Surace M, et al. Selected food intake and risk of
endometriosis. Hum Reprod 2004; 19:1755.
65. Cahill DJ. What is the optimal medical management of infertility and minor
endometriosis? Analysis and future prospects. Hum Reprod 2002; 17:1135.

66. Hughes E, Fedorkow D, Collins J, Vandekerckhove P. Ovulation suppression for


endometriosis. Cochrane Database Syst Rev 2000; :CD000155.
67. Benaglia L, Somigliana E, Vighi V, et al. Rate of severe ovarian damage following
surgery for endometriomas. Hum Reprod 2010; 25:678.
68. Fedele L, Bianchi S, Zanconato G, et al. Is rectovaginal endometriosis a progressive
disease? Am J Obstet Gynecol 2004; 191:1539.
69. Shaw RW. Treatment of endometriosis. Lancet 1992; 340:1267.
70. Vercellini P, Crosignani PG, Somigliana E, et al. Medical treatment for rectovaginal
endometriosis: what is the evidence? Hum Reprod 2009; 24:2504.
71. Ferrero S, Camerini G, Ragni N, et al. Norethisterone acetate in the treatment of
colorectal endometriosis: a pilot study. Hum Reprod 2010; 25:94.
72. Vercellini P, Pietropaolo G, De Giorgi O, et al. Treatment of symptomatic rectovaginal
endometriosis with an estrogen-progestogen combination versus low-dose norethindrone
acetate. Fertil Steril 2005; 84:1375.
73. Donnez J, Nisolle M, Gillerot S, et al. Rectovaginal septum adenomyotic nodules: a
series of 500 cases. Br J Obstet Gynaecol 1997; 104:1014.
74. Chapron C, Bourret A, Chopin N, et al. Surgery for bladder endometriosis: long-term
results and concomitant management of associated posterior deep lesions. Hum Reprod
2010; 25:884.
75. Busacca M, Chiaffarino F, Candiani M, et al. Determinants of long-term clinically
detected recurrence rates of deep, ovarian, and pelvic endometriosis. Am J Obstet
Gynecol 2006; 195:426.
76. Vercellini P, Pietropaolo G, De Giorgi O, et al. Reproductive performance in infertile
women with rectovaginal endometriosis: is surgery worthwhile? Am J Obstet Gynecol
2006; 195:1303.
77. Darai E, Ackerman G, Bazot M, et al. Laparoscopic segmental colorectal resection for
endometriosis: limits and complications. Surg Endosc 2007; 21:1572.
78. Minelli L, Fanfani F, Fagotti A, et al. Laparoscopic colorectal resection for bowel
endometriosis: feasibility, complications, and clinical outcome. Arch Surg 2009; 144:234.
79. Dara E, Bazot M, Rouzier R, et al. Outcome of laparoscopic colorectal resection for
endometriosis. Curr Opin Obstet Gynecol 2007; 19:308.

80. Dubernard G, Rouzier R, David-Montefiore E, et al. Urinary complications after surgery


for posterior deep infiltrating endometriosis are related to the extent of dissection and to
uterosacral ligaments resection. J Minim Invasive Gynecol 2008; 15:235.
81. Koninckx PR, Timmermans B, Meuleman C, Penninckx F. Complications of CO2-laser
endoscopic excision of deep endometriosis. Hum Reprod 1996; 11:2263.
82. Roman H, Loisel C, Resch B, et al. Delayed functional outcomes associated with surgical
management of deep rectovaginal endometriosis with rectal involvement: giving patients
an informed choice. Hum Reprod 2010; 25:890.
83. Practice bulletin no. 114: management of endometriosis. Obstet Gynecol 2010; 116:223.