All topics are updated as new evidence becomes available and our peer review process is complete.Literature review current through: Mar 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 lifelong management plan with the goal ofmaximizing the use of medical treatment and avoiding repeated surgical procedures” [1]. Despite extensiveresearch, the optimal management of endometriosis is unclear. This topic will review medical and surgical optionsfor treating women with this disease. Clinical features and diagnosis of endometriosis, as well as management ofthoracic endometriosis, are discussed separately. (See "Pathogenesis, clinical features, and diagnosis ofendometriosis" 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 evidencethat one medical therapy is superior to another for managing pelvic pain due to endometriosis, or that any type ofmedical treatment will affect future fertility. Therefore, treatment decisions are individualized, taking into accountthe severity of symptoms, the extent and location of disease, whether there is a desire for pregnancy, the age ofthe patient, medication side effects, surgical complication rates, and cost.
Treatment options include:
Laparoscopy is the gold standard for establishing the diagnosis of endometriosis, and provides an opportunity forconservative surgical treatment. Therapeutic intervention is desirable at the time of diagnosis to ablate or exciseimplants and adhesions, thus potentially preventing or delaying disease or symptom progression. Early surgicaltherapy also avoids the expense and side effects of medical therapy. Potential disadvantages include inadvertentdamage to adjacent organs (especially the bowel and bladder), postoperative infectious complications, andmechanical trauma to pelvic structures that may result in greater adhesion formation (see "Endometriosis: Surgicalmanagement of pelvic pain", section on 'Conservative versus definitive surgery').
After the initial diagnostic procedure, expectant management is considered primarily for two groups of patients:
®®
Expectant management
Analgesia
Hormonal medical therapy
Estrogenprogestin oral contraceptives, cyclic or continuous•
Gonadotropinreleasing 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 ofthe uterus and possibly the ovaries)
Combination therapy in which medical therapy is given before and/or after surgery
women with no or minimal symptoms and perimenopausal women. Although relief of symptoms is not as importantfor asymptomatic or minimally symptomatic women, these patients may benefit from therapy to retard progressionof the disease because studies suggest that endometriosis is a progressive disease in most women [2]. Whilemost studies suggest that oral estrogenprogestin contraceptives reduce the incidence of endometriosis, somesuggest no effect or a slight increase [35].
After menopause, endometriotic implant growth is suppressed as a result of markedly reduced ovarian estrogenproduction. Therefore, perimenopausal women with tolerable symptoms may opt for expectant management untilmenopause to avoid the side effects and cost of treatment. Alternatively, analgesia with nonsteroidalantiinflammatory drugs (NSAIDs) may provide acceptable results over the shortterm. Young women withsignificant symptoms generally require more aggressive medical or surgical therapy.
TREATMENT OF PELVIC PAIN — Women with pelvic pain and suspected endometriosis may be managed withempiric medical therapy prior to establishing a definitive diagnosis by laparoscopy [6,7]. We generally suggestanalgesics and/or combined oral estrogenprogestin contraceptives for women with no more than mild pelvic painand a GnRH agonist for those with moderate to severe pelvic pain. The advantages and disadvantages of medicaltherapy of pelvic pain in women with endometriosis are listed in the table (table 1). Although 80 to 90 percent ofpatients will have some improvement in symptoms with medical therapy, medical interventions neither enhancefertility nor diminish endometriomas or adhesions [810]. Therefore, women with suspected endometriomas andadvanced 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 inwomen with endometriosis. In observational studies, the efficacy of analgesics was limited to pain that was nomore than minimal [8]. Although NSAIDs are commonly used for analgesia, there are no high quality data showingthat they are effective for managing pain due to endometriosis or more effective than other agents [11]. Use ofNSAIDs is based on their ready availability, low cost, acceptable side effect profile, and evidence fromrandomized clinical trials consistently demonstrating that they are effective treatment of primary dysmenorrhea.(See "Treatment of primary dysmenorrhea in adult women".)
Estrogenprogestin oral contraceptives — Estrogenprogestin oral contraceptives (OCs) are a good choicefor women with minimal or mild pain who also want to prevent pregnancy. An advantage of OCs over most otherhormonal interventions is that they can be taken indefinitely.
A placebocontrolled 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 [35,1217]. The purported therapeuticmechanism 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 lowdose cyclic OC to a GnRH agonist (goserelin) reported that both drugs provided significant relief of pain, butgoserelin was superior for treatment of dyspareunia [18,19]. Data on the comparative efficacy of continuous OCsare inconsistent:
Both trials were welldesigned, but the second study was limited by the small number of patients and high dropout
A randomized trial including 133 women with relapse of endometriosisassociated pain compared treatmentwith a GnRH agonist plus addback therapy, a GnRH agonist alone, and continuous monophasic OCs for 12months [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 GnRHagonist plus addback therapy had the highest quality of life scores.
In contrast, a randomized trial including 47 women with endometriosisassociated pelvic pain that directlycompared use of continuous monophasic OCs to a GnRH agonist (leuprolide with addback) for 48 weeksfound the regimens were equally effective in reduction of pain [21].
Thus, it is unclear whether a cyclic, continuous, or tricycle regimen is most effective [8]. If pain does not respondwell to cyclic therapy, switching to continuous OC administration may be effective [22]. A monophasic pill isadequate; there is no evidence that a triphasic pill has any advantages for treatment of endometriosisrelated pain.The clinical regimen for continuous or extended use of OCs is described separately. (See "Hormonal contraceptionfor suppression of menstruation", section on 'Extended and continuous use of contraceptive pills'.)
Nonoral estrogenprogestin contraceptives (ring, patch) may also be effective, but have not been studiedextensively [23].
Failure of initial medical therapy — We offer hormonal interventions other than OCs to women with early stagedisease who are not achieving adequate pain relief after a three to sixmonth trial with analgesics or OCs and tothose with recurrent mild endometriosis and pain. The rationale for use of hormonal intervention is that altering thepatient's estrogen/progesterone profile should affect the course of the disease since ovarian steroids affect thegrowth 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 areduction in pelvic pain.
The three hormonal interventions (other than OCs) most commonly used to treat endometriosis are gonadotropinreleasing 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 associatedwith endometriosis. Randomized trials have shown that GnRH agonists are more effective than placebo and aseffective as other medical therapies for relieving pain and reducing the size of endometriotic implants [24]. Withaddback therapy, side effects are often better tolerated than those associated with a progestin or danazol. Similarto 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 anempiric trial of GnRH agonist therapy, without surgical/histological confirmation of disease, is reasonable inpatients with dysmenorrhea or chronic pelvic pain who have not responded to NSAIDs or OCs, and in whom othercauses 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, andtesting for chlamydia and gonorrhea infection, are obtained to screen for a chronic infectious or inflammatoryprocess. 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 foundseparately. (See "Gonadotropin releasing hormone agonists for longterm treatment of endometriosis".)
Progestins — Progestins inhibit endometriotic tissue growth by causing decidualization initially, and thenatrophy. They also inhibit pituitary gonadotropin secretion and ovarian hormone production.
In randomized trials and prospective observational studies, progestins alone, at appropriate doses, were aneffective treatment of pelvic pain caused by endometriosis: over 80 percent of women had partial or complete painrelief with this therapy [2630]. The effectiveness of progestins was best illustrated in a multicenter randomizedtrial including 274 women with surgically diagnosed endometriosis who were treated with intramuscular injectionsof DMPASC (104 mg) or leuprolide (11.25 mg) over a sixmonth interval [29]. Use of DMPA was associated witha significant reduction in dysmenorrhea, dyspareunia, pelvic pain, pelvic tenderness, and pelvic induration at 12months followup, 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 treatmentis less welldocumented. A few studies have reported significantly reduced implant scores (determined at
There is no evidence that highdose oral progestin treatment is associated with the bone loss observed with GnRHagonists. Indeed, 5 mg/day of norethindrone addback has been shown to diminish the bone loss associated withGnRH agonist therapy. Progestins also do not have as detrimental an impact on lipids as danazol. In addition,highdose 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 uterinebleeding/spotting, and mood changes (eg, depression). For these reasons, we feel GnRH agonists remain the firstline treatment choice, but progestinonly 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,sideeffect profile of the various drugs, and patient preference.
Duration of therapy — Most clinical trials of progestin therapy have been limited to 6 or 12 months duration forpractical reasons. Based on clinical experience in patients with endometriosis and other disorders, progestintherapy can be extended indefinitely, if effective and welltolerated. Bone loss is a concern with longtermadministration of DMPA or high dose oral MPA, especially in women with risk factors for osteoporosis, but bonedensity generally improves if the woman returns to normal ovulatory function and estrogen production. (See "Drugsthat affect bone metabolism", section on 'Medroxyprogesterone acetate' and "Depot medroxyprogesterone acetatefor contraception", section on 'Reduction in bone mineral density'.) Longterm use of norethindrone acetate can
Oral medroxyprogesterone acetate (MPA) (10 mg three times a day, maximum total dose 100 mg daily) ornorethindrone acetate (5 mg daily and increased by 2.5 mg every two weeks if pain persists, maximum totaldose 15 mg daily; however, most patients become amenorrheic at daily doses of 5 to 10 mg). Treatment iscontinued for sixmonths [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 effectsinclude 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 forcontraception".)
Use of the levonorgestrelreleasing intrauterine device (LNGIUD) after postoperative treatment ofendometriosis has been evaluated in several small randomized trials [3540]. At approximately oneyearfollowup, most trials found that the LNGIUD resulted in a significant improvement compared withpretreatment testing or expectant management in measures of chronic pelvic pain and dysmenorrhea, but notof dyspareunia. The LNGIUD was equally or less effective than GnRH agonists in preventing recurrence ofchronic pelvic pain or dysmenorrhea following surgery [38,39]. Irregular menstrual bleeding and amenorrheaare common side effects, but in contrast to depot medroxyprogesterone acetate, bone density is preserved[36]. Each LNGIUD has sufficient LNG to be effective for five years. After five years of use, the deviceshould be removed, but can be replaced with a new device if appropriate. The LNGIUD has few systemicside 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 endometriosisrelated pain (dyspareunia,dysmenorrhea, nonmenstrual pelvic pain) [41,42]. The therapeutic effect and sideeffect profile werecomparable to DMPA [41]. Pain was reduced by at least 50 percent after six months of use and maintainedfor 12 months.
A randomized trial including 253 women compared the efficacy and safety of dienogest against leuprolideacetate for treatment of pain associated with endometriosis [43]. Dienogest 2 mg/day orally was equivalentin efficacy to leuprolide at standard dose in relieving the pain associated with endometriosis, but wasassociated with fewer hypoestrogenic effects (flushes, reduction in bone mineral density) and moreunscheduled bleeding.
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 longterm therapy.
Longterm use of the LNGIUD or the etonogestrel implant does not significantly affect bone mineral density orlipid levels.
Progesterone antagonists — Progesterone antagonists and selective progesterone receptor modulators havealso been used successfully in pilot studies of treatment of endometriosis [45]. Use of these agents led to areduction of both nonmenstrual pelvic pain and dysmenorrhea. An advantage of these agents is that they suppressgrowth of endometrial cells without suppressing estrogen's effects on other tissues. However, chronic use ofprogesterone antagonists appears to create histological changes in the endometrium (cystic glandular dilatation)that resemble endometrial hyperplasia [46]. The clinical significance of these changes requires furtherinvestigation. (See "Therapeutic use and adverse effects of progesterone receptor antagonists and selectiveprogesterone receptor modulators", section on 'Endometriosis'.)
Danazol — Danazol is effective in resolving implants when treating mild or moderate stages of disease andover 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 asignificant decrease in the level of pelvic pain, lower back pain, defecation pain, and total pain in those treatedwith danazol [27]. The improvement in pain scores was still present six months after discontinuation of danazoltherapy.
Danazol is a 19nortestosterone derivative with progestinlike effects. Its mechanisms of action include inhibitionof pituitary gonadotropin secretion, direct inhibition of endometriotic implant growth, and direct inhibition of ovarianenzymes responsible for estrogen production. Danazol is given orally in divided doses ranging from 400 to 800 mgdaily, generally for six months.
Most women taking danazol have side effects that can be dosedependent, and a small percentage of patientsdiscontinue 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, moodchanges, and depression. Androgenic side effects associated with use of danazol are not treatable except bylowering the dose. By comparison, the hypoestrogenic symptoms produced by GnRH agonists can be minimizedby addback therapy.
Aromatase inhibitors — Traditional hormonal interventions for endometriosis have targeted ovarian estrogenproduction or antagonized estrogen action. Although not approved for the treatment of pelvic pain caused byendometriosis, use of aromatase inhibitors is a novel, promising approach [49]. These agents appear to regulatelocal estrogen formation within the endometriotic lesions themselves, in addition to inhibiting estrogen production inthe ovary, brain, and periphery (eg, adipose tissue) [49]. In endometriotic tissue, prostaglandin E2 stimulates botharomatase overexpression and activity, which results in local production of estrogens from androgens. Estrogen, inturn, 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 (offlabel) tointerrupt this pathway in the treatment of severe endometriosis [5158]. A systematic review of these studiesconcluded 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 areanastrozole (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 beused as single agents in premenopausal women because they stimulate FSH release and cause multifollicularcyst 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 estrogenprogestin contraceptive [55] to suppressfollicular development.
For patients in whom use of a GnRH agonist or oral estrogenprogestin contraceptive is not possible,norethindrone acetate (5 mg) is another option. In fact, the combination of letrozole and norethisterone acetate wasmore effective in reducing pain and deep dyspareunia in women with rectovaginal endometriosis thannorethisterone 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 acupuncturefound only one randomized trial that met inclusion criteria [62]. In that trial (n = 67), auricular acupuncture wassignificantly 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 alower risk of developing endometriosis was associated with a high intake of green vegetables and fruit and anincreased risk with intake of beef or other red meat or ham [64]. There was no alteration of risk of endometriosiswith consumption of other food items tested, including alcohol, coffee, fish and milk. Several studies haveaddressed diet and dysmenorrhea, but not exclusively in patients with endometriosis. (See "Treatment of primarydysmenorrhea in adult women", section on 'Diet and vitamins'.)
Surgical management — Surgery may be indicated for management of endometriosis that cannot be treated withmedical therapy or to provide a definitive diagnosis. Surgical management of endometriosis is discussed in detailseparately. (See "Endometriosis: Surgical management of pelvic pain".)
Preoperative and postoperative medical therapy
Preoperative and postoperative medical therapy is discussed in detail separately. (See "Endometriosis: Surgicalmanagement of pelvic pain", section on 'Postoperative medical therapy' and "Endometriosis: Surgical managementof pelvic pain", section on 'Preoperative medical suppressive therapy'.)
TREATMENT OF INFERTILITY — Although endometriosis can reduce fecundability (ie, the probability ofconceiving during a monthly cycle), it does not usually completely prevent conception. The mechanism forimpaired fertility may involve anatomic distortion from pelvic adhesions and endometriomas and/or production ofsubstances (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]. Astepwise 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 oridentified at the time of evaluation for a pelvic mass. Medical therapy is unlikely to result in complete regression oflarge endometriomas and precludes a definitive histologic diagnosis; therefore, surgery is the preferred therapeuticapproach. Asymptomatic endometriomas are often removed to confirm the diagnosis, exclude malignancy, andprevent complications, such as rupture or torsion requiring emergency surgery. However, ovarian reserve can bediminished following surgical excision [67].
Management of ovarian endometriomas is discussed in more detail separately. (See "Diagnosis and managementof ovarian endometriomas".)
TREATMENT OF SYMPTOMS RELATED TO DEEP ENDOMETRIOSIS — Deep infiltrating endometriosis is aterm 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 müllerianremnants.
Asymptomatic disease is managed expectantly [68]. Medical therapy is appropriate for women with bothersomesymptoms, except those with obstructive uropathy or symptomatic bowel stenosis. Although medical therapy ofsymptomatic disease has generally been reported to be ineffective or transiently effective, with recurrence ratesapproaching 70 percent [69], endometriosis is a chronic disease and cessation of medical therapy may account forthe high frequency of symptom recurrence. A review of studies of various hormonal treatments of rectovaginalendometriosis found that most patients receiving medical therapy for 6 to 12 months reported a significantreduction in dysmenorrhea and painful intercourse and defecation during treatment, but recurrence rates were highwhen medical therapy was discontinued [70].
Either a continuous estrogen–progestin combination or lowdose norethindrone can be used. In women withrectovaginal or colorectal endometriosis, continuous norethisterone acetate therapy (2.5 mg/day) for 12 monthshas been reported to improve pelvic pain, dyspareunia, dyschezia, diarrhea, and intestinal cramping, but did nothave 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 tractsymptoms [73,74]; however, recurrence rates of 30 and 43 percent at four and eight years followup, respectively,have been reported [75]. Medical treatment rather than repeat surgery may be useful in women with persistentsymptoms [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 inthe rectovaginal septum and rectal wall dissection are often necessary and require the skill of an experiencedsurgeon. Performing hysterectomy and bilateral salpingoophorectomy alone is inadequate definitive therapy ifendometriosis 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 beenreported to result in longterm relief of symptoms [74].
Surgery for deep endometriosis is associated with a relatively high risk of postoperative complications, such asdenovo or worsening voiding dysfunction, rectal dysfunction, and rectovaginal fistula [7882].
TREATMENT OF LESIONS OF NONREPRODUCTIVE ORGANS — Ovarian suppression with GnRH agonistsis probably the optimum initial therapy for symptomatic extrapelvic endometriosis [83]. However, obstruction ofthe ureter or bowel should be treated surgically. (See "Thoracic endometriosis".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, “The Basics” and“Beyond the Basics.” The Basics patient education pieces are written in plain language, at the 5 to 6 gradereading level, and they answer the four or five key questions a patient might have about a given condition. Thesearticles are best for patients who want a general overview and who prefer short, easytoread materials. Beyondthe Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are writtenat the 10 to 12 grade reading level and are best for patients who want indepth information and are comfortablewith some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or email thesetopics 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.)
SUMMARY AND RECOMMENDATIONS
th th
th th
Basics topics (see "Patient information: Endometriosis (The Basics)")
Beyond the Basics topics (see "Patient information: Endometriosis (Beyond the Basics)")
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 ofpelvic pain due to endometriosis. There is also no high quality evidence that medical or surgical interventionwill 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, medicationside effects, surgical complication rates, and cost. (See 'General approach' above.)
An initial diagnostic laparoscopy for establishing the presence of endometriosis provides an opportunity forablation or excision of implants and adhesions, thus potentially preventing or delaying disease or symptomprogression. This approach should be considered in patients with suspected advanced stages of disease (ie,endometriomas) and may benefit women with endometriosisassociated infertility. Early surgical therapy alsoavoids the expense and side effects of medical therapy. (See 'General approach' above.)
Empiric medical therapy with nonsteroidal antiinflammatory drugs, oral contraceptives, or GnRH agonistsmay be used in women with pelvic pain and suspected endometriosis, prior to establishing the diagnosissurgically. This may provide sufficient pain relief and avoid a laparoscopy. There is insufficient longtermfollowup of patients managed initially with medical therapy to assess symptom recurrence or the eventualneed for surgical intervention.
For women with no more than mild pelvic pain, we suggest nonsteroidal antiinflammatory drugs over othermedical 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 antiinflammatorydrugs and/or combined oral contraceptives, and those with recurrent mild endometriosis and pain, wesuggest 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, irregularuterine 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, wesuggest treatment with a progestin (Grade 2B). Progestins have a more favorable side effect profile thandanazol. (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, orobstruction of the bowel or urinary tract), we suggest surgical rather than medical therapy (Grade 2C). Wealso suggest surgical intervention for women whose symptoms have failed to resolve or have worsenedunder medical management (Grade 2C). (See 'Surgical management' above.)
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.)
Medical therapy is unlikely to result in complete regression of large endometriomas and precludes a definitivehistologic diagnosis. Therefore, surgery is the preferred therapeutic approach. (See 'Treatment of pelvicmass' above.)
For women with pelvic pain, dyspareunia, or painful defecation related to deep endometriosis, we suggest
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REFERENCES
1. Practice Committee of American Society for Reproductive Medicine. Treatment of pelvic pain associatedwith endometriosis. Fertil Steril 2008; 90:S260.
2. Mahmood TA, Templeton A. The impact of treatment on the natural history of endometriosis. Hum Reprod1990; 5:965.
3. Vessey MP, VillardMackintosh L, Painter R. Epidemiology of endometriosis in women attending familyplanning 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 benignovarian 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 BulletinsGynecology. ACOG practice bulletin. Medical management ofendometriosis. Number 11, December 1999 (replaces Technical Bulletin Number 184, September 1993).Clinical management guidelines for obstetriciangynecologists. Int J Gynaecol Obstet 2000; 71:183.
8. Dunselman GA, Vermeulen N, Becker C, et al. ESHRE guideline: management of women withendometriosis. Hum Reprod 2014; 29:400.
9. American College of Obstetricians and Gynecologists. Medical management of endometriosis. ACOGpractice 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 SystRev 2007; :CD000155.
11. Allen C, Hopewell S, Prentice A, Gregory D. Nonsteroidal antiinflammatory drugs for pain in women withendometriosis. Cochrane Database Syst Rev 2009; :CD004753.
12. Harada T, Momoeda M, Taketani Y, et al. Lowdose oral contraceptive pill for dysmenorrhea associated withendometriosis: a placebocontrolled, doubleblind, randomized trial. Fertil Steril 2008; 90:1583.
13. Buttram VC Jr. Cyclic use of combination oral contraceptives and the severity of endometriosis. Fertil Steril1979; 31:347.
14. Strathy JH, Molgaard CA, Coulam CB, Melton LJ 3rd. Endometriosis and infertility: a laparoscopic study ofendometriosis 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 gonadotropinreleasing hormone agonist versus a lowdose 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. Addback 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 endometriosisassociated 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
24. Brown J, Pan A, Hart RJ. Gonadotrophinreleasing hormone analogues for pain associated withendometriosis. Cochrane Database Syst Rev 2010; :CD008475.
25. Ling FW. Randomized controlled trial of depot leuprolide in patients with chronic pelvic pain and clinicallysuspected 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 ofendometriosis. Obstet Gynecol 1988; 72:323.
27. Telimaa S, Puolakka J, Rönnberg L, Kauppila A. Placebocontrolled comparison of danazol and highdosemedroxyprogesterone acetate in the treatment of endometriosis. Gynecol Endocrinol 1987; 1:13.
28. Prentice A, Deary AJ, Bland E. Progestagens and antiprogestagens for pain associated with endometriosis.Cochrane Database Syst Rev 2000; :CD002122.
29. Crosignani PG, Luciano A, Ray A, Bergqvist A. Subcutaneous depot medroxyprogesterone acetate versusleuprolide 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 theevidence. Fertil Steril 1997; 68:393.
31. Dawood MY, Obasiolu CW, Ramos J, KhanDawood FS. Clinical, endocrine, and metabolic effects of twodoses 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 GnRHagonistleuprorelin acetate and the gestagen lynestrenol in the treatment of severe endometriosis. GynecolEndocrinol 2001; 15:202.
33. Schlaff WD, Carson SA, Luciano A, et al. Subcutaneous injection of depot medroxyprogesterone acetatecompared with leuprolide acetate in the treatment of endometriosisassociated pain. Fertil Steril 2006;85:314.
34. Vercellini P, De Giorgi O, Oldani S, et al. Depot medroxyprogesterone acetate versus an oral contraceptivecombined with verylowdose danazol for longterm treatment of pelvic pain associated with endometriosis.Am J Obstet Gynecol 1996; 175:396.
36. Wong AY, Tang LC, Chin RK. Levonorgestrelreleasing intrauterine system (Mirena) and Depotmedroxyprogesterone acetate (Depoprovera) as longterm maintenance therapy for patients with moderateand 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 levonorgestrelreleasing intrauterine deviceversus 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 intrauterinesystem 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 painrelated to severe endometriosis: levonorgestrelreleasing intrauterine system versus gonadotropinreleasinghormone analogue. Fertil Steril 2011; 95:492.
40. Tanmahasamut P, Rattanachaiyanont M, Angsuwathana S, et al. Postoperative levonorgestrelreleasingintrauterine system for pelvic endometriosisrelated pain: A randomized trial. Obstet Gynecol 2012.
41. Walch K, Unfried G, Huber J, et al. Implanon versus medroxyprogesterone acetate: effects on pain scoresin patients with symptomatic endometriosisa pilot study. Contraception 2009; 79:29.
42. Yisa SB, Okenwa AA, Husemeyer RP. Treatment of pelvic endometriosis with etonogestrel subdermalimplant (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 painfulsymptoms of endometriosis: a 24week, randomized, multicentre, openlabel trial. Hum Reprod 2010;25:633.
44. Cirkel, U, Schweppe, KW, Ochs, H, et al. Effects of LHRH agonist therapy in the treatment ofendometriosis. In: Gonadotropin downregulation 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
4year followup. 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, AlTurki 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 postsurgical administration of goserelin plus anastrozole
compared to goserelin alone in patients with severe endometriosis: a prospective randomized trial. HumReprod 2004; 19:160.
59. Nawathe A, Patwardhan S, Yates D, et al. Systematic review of the effects of aromatase inhibitors on painassociated with endometriosis. BJOG 2008; 115:818.
60. Mousa NA, Bedaiwy MA, Casper RF. Aromatase inhibitors in the treatment of severe endometriosis. ObstetGynecol 2007; 109:1421.
61. Ferrero S, Camerini G, Seracchioli R, et al. Letrozole combined with norethisterone acetate compared withnorethisterone acetate alone in the treatment of pain symptoms caused by endometriosis. Hum Reprod2009; 24:3033.
62. Zhu X, Hamilton KD, McNicol ED. Acupuncture for pain in endometriosis. Cochrane Database Syst Rev2011; :CD007864.
63. Xiang D, Situ Y, Liang X, et al. Ear acupuncture therapy for 37 cases of dysmenorrhea due toendometriosis. J Tradit Chin Med 2002; 22:282.
64. Parazzini F, Chiaffarino F, Surace M, et al. Selected food intake and risk of endometriosis. Hum Reprod2004; 19:1755.
65. Cahill DJ. What is the optimal medical management of infertility and minor endometriosis? Analysis andfuture prospects. Hum Reprod 2002; 17:1135.
66. Hughes E, Fedorkow D, Collins J, Vandekerckhove P. Ovulation suppression for endometriosis. CochraneDatabase Syst Rev 2000; :CD000155.
67. Benaglia L, Somigliana E, Vighi V, et al. Rate of severe ovarian damage following surgery forendometriomas. Hum Reprod 2010; 25:678.
68. Fedele L, Bianchi S, Zanconato G, et al. Is rectovaginal endometriosis a progressive disease? Am J ObstetGynecol 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
estrogenprogestogen combination versus lowdose 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: longterm 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 longterm 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. Daraï 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, DavidMontefiore E, et al. Urinary complications after surgery for posterior deep
infiltrating endometriosis are related to the extent of dissection and to uterosacral ligaments resection. JMinim Invasive Gynecol 2008; 15:235.
81. Koninckx PR, Timmermans B, Meuleman C, Penninckx F. Complications of CO2laser endoscopic excisionof deep endometriosis. Hum Reprod 1996; 11:2263.
82. Roman H, Loisel C, Resch B, et al. Delayed functional outcomes associated with surgical management ofdeep rectovaginal endometriosis with rectal involvement: giving patients an informed choice. Hum Reprod2010; 25:890.
83. Practice bulletin no. 114: management of endometriosis. Obstet Gynecol 2010; 116:223.
Disclosures: Robert S Schenken, MD Nothing to disclose. Robert L Barbieri, MD Nothing to disclose. Kristen Eckler, MD, FACOGNothing to disclose.Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multilevel review process, and through requirements for references to be provided to support the content. Appropriately referencedcontent is required of all authors and must conform to UpToDate standards of evidence.Conflict of interest policy
