Pii: s0015-0282(02)04216-4

FERTILITY AND STERILITY௡
VOL. 78, NO. 5, NOVEMBER 2002Copyright 2002 American Society for Reproductive Medicine Published by Elsevier Science Inc.
Printed on acid-free paper in U.S.A.
Consensus statement for the management
of chronic pelvic pain and endometriosis:
proceedings of an expert-panel consensus
process
Joseph C. Gambone, D.O., M.P.H.,a,b Brian S. Mittman, Ph.D.,b,cMalcolm G. Munro, M.D.,a Anthony R. Scialli, M.D.,d Craig A. Winkel, M.D., M.B.A.,dand the Chronic Pelvic Pain/Endometriosis Working Group UCLA Medical School, Los Angeles, California Objective: To develop recommendations for the medical and surgical care of women who present with
chronic pelvic pain (CPP) and are likely to have endometriosis as the underlying cause.
Design: An expert panel comprised of practicing gynecologists from throughout the United States and experts
in consensus guideline development was convened. After completion of a structured literature search and
creation of draft algorithms by an executive committee, the expert panel of Ͼ50 practicing gynecologists met
for a 2-day consensus conference during which the clinical recommendations and algorithms were reviewed,
refined, and then ratified by unanimous or near-unanimous votes.
Patient(s): Women presenting with CPP who are likely to have endometriosis as the underlying cause.
Main Outcome Measure(s): None.
Conclusion(s): Chronic pelvic pain frequently occurs secondary to nongynecologic conditions that must be
considered in the evaluation of affected women. For women in whom endometriosis is the suspected cause of
the pain, laparoscopic confirmation of the diagnosis is unnecessary, and a trial of medical therapy, including
second-line therapies such as danazol, GnRH agonists, and progestins, is justified provided that there are no other indications for surgery such as the presence of a suspicious adnexal mass. When surgery is necessary, laparoscopic approaches seem to offer comparable clinical outcomes to those performed via laparotomy, but with reduced morbidity. The balance of evidence supports the use of adjuvant postoperative medical therapy after conservative surgery for CPP. There is some evidence that adjuvant presacral neurectomy adds benefit for midline pain, but currently, there is inadequate evidence to support the use of uterosacral nerve ablation or uterine suspension. Hysterectomy alone has undocumented value in the surgical management of women with endometriosis-associated CPP. (Fertil Steril௡ 2002;78:961–72. 2002 by American Society for Repro- Key Words: Pain, endometriosis, guidelines, consensus
California 90095-1740(FAX: 310-206-3670; E-mail: jgambone@mednet.
ucla.edu).
Chronic pelvic pain (CPP) and endometrio- age of women with CPP who also have endo- sis are two of the more common symptomatic metriosis range as high as 70%–90% (3–5).
conditions in women’s healthcare. Ten percent The natural history of endometriosis remains Angeles, California.
bDepartment of Veterans of visits to gynecologists, 20% of laparoscopic open to speculation because no prospective ob- procedures performed by gynecologists, and servational studies have been undertaken or Յ18% of hysterectomies are performed for reported. Although endometriosis has been ob- CPP (1, 2). Chronic pelvic pain has multiple served in females as young as 10.5 years, the etiologies, and in many women a specific cause disease usually presents during the reproduc- may remain uncertain or unknown. Endometri- tive years and is stable or regresses in 50% of osis is a common cause of CPP. Currently there women (6, 7), whereas in the remainder, pro- exist no valid epidemiological data to establish gression is generally slow. The type of CPP the true incidence of endometriosis in women most commonly attributed to endometriosis is 0015-0282/02/$22.00PII S0015-0282(02)04216-4 with CPP. However, estimates of the percent- dysmenorrhea, but both cyclic and noncyclic pain as well as deep dyspareunia and dyschesia are de- The consensus panel met to review the evidence summa- ries and draft materials during a 2-day consensus conference.
The conference began with general sessions addressing con- Evidence regarding the efficacy and other characteristics sensus statement goals and methods, followed by individual of available treatments, medical and surgical, for CPP and subcommittee meetings to review and revise the draft mate- endometriosis is incomplete. As a result, management of rials. Ten consensus panel members were assigned by ran- women with CPP thought to be secondary to endometriosis dom drawing to each of three subcommittees which ad- varies widely and may often be suboptimal and costly. These dressed [1] diagnostic processes, [2] medical therapies, and variations and opportunities for improvement, as well as the [3] surgical therapies. Each subcommittee reviewed the rel- availability of new evidence and changing opinions regard- evant evidence summaries and draft algorithms and recom- ing optimal management, suggest the potential value of an mendations and revised the drafts after extensive discussion.
evidence-based consensus statement concerning the most The subcommittee presented their revisions to the entire appropriate care for these patients based on a combination of panel in a subsequent plenary session, with ratifications by expert opinion and a current literature review.
formal vote. All three subcommittees’ final algorithms and Herein we describe the methodology and results of an recommendation statements were approved by unanimous or expert-panel consensus statement development process. The available evidence for clinical management guidance is alsosummarized. The consensus recommendations and algo- SUMMARY OF THE EVIDENCE
rithms do not address the additional diagnostic or treatmentsteps indicated in women for whom the presenting CPP Herein we present the available evidence relevant to the appears to have a cause other than endometriosis, or for important areas of clinical management of CPP that occurs whom other conditions (including pelvic masses) would in association with endometriosis. Although some aspects of necessarily complicate management. Similarly, the consen- the diagnosis and treatment of CPP have been studied ex- sus statement does not address treatment for infertility asso- tensively, well-designed studies regarding other important ciated with endometriosis and provides only partial guidance aspects have not been reported or were not found during this for women with CPP that is believed to be secondary to endometriosis (whether or not infertility is demonstrated orsuspected), for whom immediate fertility is a primary goal.
Medical Therapy
Nonsteroidal Anti-Inflammatory Drugs
CONSENSUS STATEMENT
DEVELOPMENT METHODS
Nonsteroidal anti-inflammatory drugs (NSAIDs) have been studied extensively in randomized controlled trials The consensus statement (comprising clinical recommen- (RCTs) for treatment of primary dysmenorrhea and are of dations and algorithms) was developed by a panel of 52 proven efficacy (11–16). Although not specifically studied practicing gynecologists and methodology experts according for noncyclic CPP, it is apparent that NSAIDs are used to accepted standards for development of clinical practice empirically as a first-line medical treatment for CPP.
guidelines and consensus statements (8 –10). Panel members Oral Contraceptives
were selected by a consensus statement executive committee(CSEC), based on practice credentials and geographic loca- High-dose estrogen–progestin combinations were initially tion. The development process included a MEDLINE liter- employed as part of a “pseudopregnancy regimen” in the ature search for articles addressing etiology and pathophys- management of symptomatic endometriosis (17). Various low-dose oral contraceptives (OCs) have been studied with- endometriosis. The initial search covered the period 1966 out placebo controls as initial management of primary dys- through August, 1999 and was updated through December, menorrhea with a high degree of success (18 –20). These 2001. The article list was reviewed by four pairs of reviewers studies included patients not screened by laparoscopy, sug- (comprising the CSEC), focusing on [1] epidemiology of gesting the possibility that patients with CPP and endome- CPP, [2] etiology, pathophysiology and impact of endome- triosis on CPP, [3] medical therapy for endometriosis and Only a single RCT of low-dose OCs for CPP and endo- CPP, and [4] surgical therapy for endometriosis and CPP.
metriosis has been published (21). In this 6-month trial, The CSEC reviewed and summarized all relevant articles cyclically administered OCs were compared with a GnRH in a series of 5- to 10-page evidence summaries. The CSEC agonist (GnRH-a) in women with laparoscopically diag- then developed preliminary diagnostic and treatment algo- nosed endometriosis. Oral contraceptives were reported to be rithms, and the summaries and initial clinical recommenda- less effective for relief of dysmenorrhea and to be of similar tions were distributed to the consensus panel members in efficacy to GnRH-a for relief of dyspareunia and nonmen- Gambone et al.
Danazol
ease, and vasomotor symptoms were all suppressed withoutsignificant change in bone density in either group. Hornstein Danazol is a synthetic androgen that inhibits ovarian et al. (50) reported 201 patients treated with depot leuprolide steroid and pituitary gonadotropin release (22). A group of acetate for 52 weeks and randomized into one of four add- four 6-month RCTs (with possible patient overlap) com- back groups. Groups received placebo, norethindrone acetate pared danazol with placebo after laparoscopic diagnosis of (5 mg/d) alone, or norethindrone acetate (5 mg/d) in con- endometriosis in which danazol was more effective than junction with conjugated equine estrogens (0.625 or 1.25 placebo (23–26). One of these studies also reported a sig- mg/d). Pain symptoms were alleviated in each treatment nificant improvement in painful symptoms after treatment arm, although the highest number of dropouts due to persis- with danazol compared with placebo in patients who had not tent or recurrent pain was noted in those receiving the higher undergone surgery (24). No other studies were found that estrogen doses. Vasomotor symptoms were suppressed in all reported the use of danazol in the management of CPP or three add-back groups. Lumbar spine bone mineral density dysmenorrhea or in patients with clinically suspected endo- decreased 3.2% in 6 months and 6.3% in 12 months without add-back, but no significant decrease was observed in any of Gonadotropin-releasing Hormone Agonist
the add-back groups. Adverse lipid changes shown withdanazol and GnRH-a consist of decreased high-density li- Gonadotropin-releasing hormone agonist effectively in- poprotein (HDL) cholesterol and increased total and low- duces a “functional oophorectomy” in treated patients, density lipoprotein (LDL) cholesterol, with greater adverse thereby dramatically reducing estradiol production. Only one effects of danazol than those of GnRH-a on lipids (32, 51).
published RCT compared a GnRH-a (leuprolide acetate) to Add-back with norethindrone acetate with or without low- placebo (27). Because most (27 of 31) placebo patients dose or high-dose equine estrogen resulted in increased HDL dropped out by 3 months because of symptoms, valid scien- and decreased LDL cholesterol (50). The mechanism of tific comparisons could not be made between the groups.
action is unclear but may be related, in part, to hepatic Nevertheless, a substantial degree of pain relief was demon- conversion of small but clinically significant amounts of norethindrone acetate to ethinyl estradiol.
The majority of studies compared GnRH-a with danazol Progestins
(400 – 800 mg/d) administered to women with laparoscopi-cally confirmed symptomatic endometriosis. A large group Medroxyprogesterone acetate (MPA) may be beneficial of studies demonstrated the danazol and GnRH-a treatment for patients with CPP secondary to known or suspected regimens to be equally efficacious (28 – 42).
endometriosis. Progestins induce decidualization and acy- Empiric use of GnRH-a was tested by RCT in 100 women clicity of endometrium and endometriotic tissue. One review with noncyclic pelvic pain who had not undergone assess- article by Vercellini et al. (52) analyzed 27 trials of various ment by laparoscopy but nevertheless had clinically sus- progestins for treatment of symptomatic endometriosis, four pected endometriosis (5). After 12 weeks of therapy with of which were RCTs (21, 53–55). Variously, progestins were depot leuprolide acetate (3.75 mg/mo), decreases in dysmen- compared with danazol (23), with danazol and an OC (24), orrhea, pelvic pain, and tenderness were noted in the treat- with a depot preparation of a GnRH-a (21), and with placebo ment group. Endometriosis was visualized at subsequent (25). Dydrogesterone (2 different doses) was found to be no laparoscopy in 78% of the leuprolide-treated and 87% of the more effective than placebo. In one 12-month trial, MPA placebo-treated groups. Women who did not present visual depot (150 mg every 90 days) used alone had effects equiv- evidence of endometriosis, however, also responded to treat- alent to those of GnRH-a. In two 6-month trials, the proges- tins desogestrel (56) or cyproterone acetate (57) were com-bined with ethinyl estradiol. Overall, odds ratios (OR) for Steroidal and nonsteroidal agents have been employed in these two non–placebo-controlled randomized trials varied the context of add-back regimens to allow maintenance of from 0.3 to 2.5, with a common nonsignificant OR of 1.1 the function and efficacy of the GnRH-a while suppressing (confidence interval [95% CI] ϭ 0.4 –3.1). Oral MPA in a side effects such as osteopenia and vasomotor symptoms. A 50-mg daily dose was effective in reducing pain scores at the number of RCTs have demonstrated the efficacy of add-back end of therapy, but the benefit was not sustained (58).
regimens with various GnRH-a for treatment of endometri-osis during 6-month courses (43– 48).
Medical Adjunctive Therapy
Two RCTs have assessed the role of add-back with depot Many of the agents reviewed above can be used before, leuprolide acetate (depot GnRH-a) during therapy for Ͼ6 after, or both before and after either conservative or radical months (49, 50). In an open-label trial of 19 patients who surgery. Adamson and Nelson (59) suggested that preoper- received GnRH-a with either norethindrone (10 mg/d p.o.) or ative medical therapy may result in less risk of injury to norethindrone (2.5 mg/d) ϩ cyclic etidronate (400 mg/d) ureters, blood vessels, and the bowel, although none of these during a 48-week trial (49), pain symptoms, extent of dis- potential benefits have been proved.
FERTILITY & STERILITY௡
Danazol has been evaluated as postoperative adjuvant diagnostic laparoscopy alone for stage I–III endometriosis- therapy in three randomized trials (60 – 62). A dose of 600 associated CPP. Ninety percent of those with improvement mg/d for 6 months after surgery was found to be equivalent at 6 months continued to demonstrate improvement at 1 year.
to 100 mg/d of MPA and to be superior to placebo although Unfortunately, the addition of uterosacral nerve ablation to side effects occurred, including bleeding, weight gain, and the surgical procedure confounded interpretation of the ef- acne (60). A randomized trial to compare a similar dose of ficacy of endometriosis destruction alone in producing pain danazol with no therapy (no placebo) for 3 postoperative relief. However, investigators from the same center per- months demonstrated no advantage with respect to pain formed a subsequent double-blind RCT in which all women recurrence (61). Morgante et al. (62) evaluated low-dose underwent laparoscopic laser vaporization of endometriosis; danazol (100 mg/d) in a cohort of women who underwent half of the women were randomized to receive uterosacral conservative laparoscopic surgery and 6 months of GnRH-a nerve ablation as well (69). At 6 months of follow-up, all therapy (62). The danazol group had lower pain scores than patients in the trial were significantly improved compared did those patients who did not use danazol after the postop- with baseline, but those with vaporization alone had pain scores that were similar to or better than those of womenwho underwent vaporization and uterosacral nerve ablation.
Despite the existence of RCTs evaluating the issue, there These findings suggest that local destruction of endometri- is controversy regarding the value of GnRH-a after conser- otic lesions is associated with improvements in pelvic pain, vative surgical therapy. An Italian group compared 3 months at least at 6 to 12 months after surgery.
of postoperative nafarelin (400 ␮g/day) with placebo nasalspray and found no difference in pain scores at 12 months Surgery Directed at Endometriosis: Type of Treatment
(63). A larger Italian multicenter RCT of 269 patients, how-ever, has shown that adjuvant GnRH-a therapy was effica- There are a number of techniques by which endometriosis cious at 6 months after conservative surgery but failed at 1 to can be removed or destroyed, and each has potential advan- tages, disadvantages, and differences in efficacy. However,no RCTs were found that compare surgical excision with In a third RCT that was done in the United States, energy-based ablation techniques that include vaporization, investigators found that women treated with a GnRH-a had fulguration, or coagulation. Winkel and Bray (67) reported a better outcomes than women treated with surgery alone (65).
24-month follow-up of women who underwent surgical Winkel and Bray (66) recently reported the results of a treatment by excision alone, laser vaporization alone, or 24-month follow-up of 240 women with endometriosis and laser vaporization plus GnRH-a. Twelve months after sur- CPP who underwent excision alone, laser ablation alone, or gery, 96% of excision patients were pain free, whereas 69% laser ablation followed by treatment with leuprolide acetate of those undergoing coagulation were without pain. At 2 for 3 to 6 months. In this nonrandomized trial, only 23% of years, the corresponding figures were 69% and 23%, respec- the ablation group was pain free at 24 months, whereas 70% tively. Although these results suggest that excision may be of the ablation plus GnRH-a–treated group remained pain superior to ablation, the retrospective design of the study leaves such a conclusion open to criticism.
Surgical Therapy
Management of Endometriosis-associated Cystic Ovarian
Evaluation of the treatment effect of surgery on endo- Masses
metriosis-associated pain is difficult because few RCTs havebeen performed and none have compared surgical manage- There exist a number of approaches to the surgical man- agement of ovarian cysts encountered in the treatment ofendometriosis, including cystectomy, simple drainage, drain- Surgery Directed at Endometriosis: Overview
age and coagulation, and drainage followed by stripping ofthe cyst lining. Not all ovarian cysts associated with endo- Sutton (67) reported that 70% of women treated for metriosis are endometriomas (in one study, none of the endometriosis with laparoscopically directed techniques excised cysts or cyst linings contained histologically dem- were improved at 1 year. Redwine (68) reported a cumula- onstrated endometriosis) (70). In another retrospective study, tive rate of recurrence and persistence (defined as visualizing however, the authors compared outcomes in 231 women endometriosis at repeat laparoscopy without regard to symp- managed laparoscopically either with fenestration and abla- toms) of 19% by 5 years. Both uncontrolled studies em- tion (n ϭ 70) or by cystectomy (n ϭ 161) (71). Reoperation ployed retrospective data collection, inconsistent approaches rates at 42 months were 23.5% after excision and 57.8% after to the measurement of symptoms, and heterogeneity of sur- fenestration and ablation. Somewhat similar results were reported by Beretta et al. (72), who performed an RCT In a double-blind RCT, Sutton et al. (69) reported the comparing cystectomy with drainage and bipolar electrosur- results of laparoscopically directed conservative surgery (la- gical coagulation of the lining in 64 women operated on via ser vaporization, adhesiolysis, uterosacral nerve ablation) vs.
laparoscopy. Although complication rates were similar, there Gambone et al.
were significantly different outcomes in favor of cystectomy results at laparotomy. Although Candiani et al. (78) found for each of the three types of pain evaluated, including that adding PSN to conservative surgery markedly reduced dysmenorrhea (15.8% vs. 52.9%), deep dyspareunia (20% the midline component of menstrual pain, in long-term fol- vs. 75%), and nonmenstrual pain (10% vs. 52.9%).
low-up, there were no differences between the two groups inthe frequency and severity of dysmenorrhea, pelvic pain, and Laparoscopy vs. Laparotomy
dyspareunia. Tjaden et al. (79) also found that the addition of The literature is replete only with comparisons of laparo- PSN to standard surgical therapy by laparotomy enhanced scopic and laparotomic surgery that include AFS stage IV pain relief for midline pain. Although this was reported as an endometriosis. Crosignani et al. (73) evaluated women with RCT, only 8 of 26 patients were randomized, and the study CPP and stage IV endometriosis after laparoscopic surgery was terminated before completion because of significant (n ϭ 47) or at the time of laparotomy (n ϭ 108) surgery reduction in midline pain experienced by the patients under- selected by the surgeon. Many of the women also received going PSN. Chen et al. (80) reported the only RCT evaluat- medical therapy after surgery. At 24 months, the laparo- ing laparoscopic PSN in 68 patients assigned to either PSN scopic and laparotomy approaches were about equally effec- or LUNA. These patients had primary dysmenorrhea and tive (approximately two thirds of patients were pain free).
were not known to have endometriosis. At 3-month follow- Recurrence rates for dysmenorrhea were 16.4% to 20.3% for up, both groups were equal in terms of symptom relief laparoscopic surgery vs. 20.3% to 27.7% for those per- (87.9% vs. 82.9%), but the efficacy of PSN was significantly formed via laparotomy; 28.6% to 33.3% for deep dyspareu- better than that of LUNA (81.8% vs. 51.4%) at 12 months.
nia for laparoscopy vs. 10.4% to 15.4% for dyspareunia; and Role of Gonadectomy and Hysterectomy
17.5% to 25% vs. 15.9% to 20.1% for nonmenstrual CPP.
Conservative surgery at laparotomy was compared with Removal of the ovaries (bilateral oophorectomy), with or the laparoscopic approach in 81 patients who required repeat without hysterectomy, is generally regarded as the most surgery for endometriosis (AFS stages I–IV) (74). They were effective procedure for women who have recurrent symp- similar with respect to recurrence rates for dysmenorrhea tomatic endometriosis and who have no desire to retain (28.6% vs. 25%), dyspareunia (25% vs. 30%), and noncyclic reproductive function. A number of investigators have eval- CPP (23% vs. 34%). Similar results were reported in 132 uated the incidence of symptom recurrence after hysterec- women with stage III and IV endometriosis who also were tomy with ovarian retention. One group demonstrated that 18 of 29 women experienced recurrent pain and 9 (31%) un-derwent reoperation after hysterectomy with ovarian reten- The incidence of pain recurrence was 19% after lapa- tion (81). Retained ovarian function had an 8.1 OR (CI ϭ rotomic surgery and 13.4% after laparoscopy in a retrospec- 2.1–31.3) of requiring reoperation for CPP. The incidence of tive study with 12-month follow-up done by Bateman et al.
persistent or recurrent CPP after hysterectomy and bilateral (76). Laparoscopic technique was associated with equivalent salpingo-oophorectomy was 10% (11 of 109).
operating time, reduced hospital stay, and a more rapidreturn to work.
Uterine Suspension Procedures
Surgery Directed at Pain Transmission
The consensus group could find no data supporting or refuting the place for uterine suspension as an adjunct in the Uterosacral Nerve Ablation. Laparoscopic uterosacral treatment of endometriosis-associated pelvic pain. Individual nerve ablation (LUNA) is designed to disrupt the efferent practitioner experience can guide the use of this procedure.
nerve fibers in the uterosacral ligament to diminish uterinepain. However, there seems to be little evidence to support CLINICAL RECOMMENDATIONS AND
the performance of this procedure. In a cohort study, Lichten ALGORITHMS
and Bombard (77) reported Ͼ80% relief from menstrualpain after LUNA that declined to 50% after 12 months. The The overall algorithm produced and approved by the double-blind RCT reported by Sutton et al. (69), discussed consensus panel (Fig. 1) provides a general guide for the previously, showed that adding LUNA to laser vaporization assessment and management of women presenting with CPP.
of endometriosis did not improve pain scores. In fact, in this Subalgorithms were created for sections A and E of the well-designed double-blinded trial, patients who had LUNA overall algorithm, as discussed below.
added to the procedure had less successful 6-month out- Section A (seen in detail in Fig. 2) addresses the diag- comes with respect to both dysmenorrhea and chronic non- nostic approach to women with CPP, including an assess- ment of patient preferences and values, leading to an initial Presacral Neurectomy. Presacral neurectomy (PSN) is a diagnostic impression. Significantly, this algorithm identifies procedure designed to interrupt sympathetic pathways from women who may have CPP secondary to diagnoses other the uterus. There have been three reported RCTs, one eval- than endometriosis (section B). Management of these clini- uating PSN as performed via laparoscopy and two that assess cal entities, although extremely important, was not consid- FERTILITY & STERILITY௡
Algorithm that delineates the steps for the assessment, diagnosis, and treatment options of patients with chronic pelvic painand presumed endometriosis: overall approach.
Gambone. Chronic pelvic pain and endometriosis. Fertil Steril 2002. ered to be within the purview of this expert panel and triosis, GI or GU problems, infections, musculoskeletal therefore was not developed further. Sections C through I problems, and psychiatric conditions, including infor- address management of the target group for the consensus mation on response to any previous treatments for en- statement. A detailed algorithm is provided for section E in dometriosis or other conditions related to the presenting Section A: Initial Diagnosis and Assessment
● Previous symptoms suspicious for endometriosis, GI or GU problems, infections, musculoskeletal problems, Clinical History
psychological or psychiatric conditions, sexual abuse,or physical abuse A thorough history of the woman’s symptoms, and pre- ● Menstrual, contraceptive, and sexual histories, in- vious diagnoses and treatments should include, but should cluding previous menstrual disorders; use of intra- uterine devices, OCs, and other contraceptive meth- ● The presenting pain, including its location, magnitude, ods; age of onset of menses; a history of all timing, relationship to physical exertion, sexual activity, pregnancy outcomes; and other reproductive tract– menses, pregnancy, abdominal distention, gastrointesti- nal (GI) and genitourinary (GU) function, as well as ● Family history of relevant clinical conditions, includ- ing malignancies and pain disorders such as endome- ● Prior and current diagnoses and treatments for endome- Gambone et al.
● Blood tests, including complete blood count with dif- ferential and erythrocyte sedimentation rate Closer view of section A of overall algorithm shown in Figure ● CA-125 (in selected cases, e.g., evidence of ascites) 1: initial assessment of patients with chronic pelvic pain andpresumed endometriosis.
● Pelvic ultrasound (if a mass is palpated)● Magnetic resonance imaging (in selected cases, e.g., if it is necessary to identify deep infiltrative disease pre-operatively, although the accuracy of magnetic reso-nance imaging for this diagnosis is controversial) Patient Preferences and Values
A thorough discussion and assessment of the patient’s preferences and values should be conducted, addressing hernear-term and long-term plans and desires regarding fertility,her attitudes and preferences regarding medical and surgicaltreatments, and other relevant issues.
Development of the Initial Impression
On the basis of the history, physical examination, labo- ratory, and any indicated imaging studies, an initial impres-sion should be developed. If one or more findings are con-sistent with a condition other than endometriosis withoutadnexal mass, then further diagnostic testing and/or treat-ment should be conducted, as appropriate (see section B ofthe algorithm). If no findings are consistent with anothergynecologic or nongynecologic diagnosis, then endometrio-sis should be strongly suspected, and first-line medical ther-apy should be considered.
Section B: Nongynecologic Causes
Gambone. Chronic pelvic pain and endometriosis. Fertil Steril 2002. When a patient’s CPP is thought to be due to nongyne- cological conditions such as irritable bowel syndrome or Physical Examination
urologic problems such as chronic cystitis or is associatedwith psychological problems secondary to physical or sexual A complete gynecologic and targeted physical examina- abuse, an appropriate workup for these nongynecologic con- tion should be conducted considering both potential gyneco- ditions is recommended. Details about specific interventions logic and nongynecologic causes of the pain as well as the for nongynecologic conditions or management of women concepts of referred pain and the existence of trigger points.
who have adnexal masses were beyond the scope of this Specifically, it should include the following: ● Pelvic exam, focusing on tenderness and its location, Section C: First-Line Medical Treatment
the presence or absence of nodularity, particularly in the Medical treatment of women with CPP suspected to be cul-de-sac, and the detection of palpable masses also in related to endometriosis should begin with a trial of NSAIDs or OCs or a combination of both. Selection of a first-line ● Abdominal exam, focusing on the presence or absence medical therapeutic agent should be based on the nature of of abdominal distention and the location of the symp- the pain (cyclic or noncyclic), contraindications to NSAIDs or OCs (including a history of GI problems), desire for ● Straight leg–raising test, focusing on its ability to in- contraception, and other factors. Nonsteroidal anti-inflam- duce lower right or left quadrant tenderness matory drugs should be used around the time of menses in Laboratory and Imaging Studies
women with cyclic pain, intermittently for those with inter-mittent cyclic pain, or continuously, based on the patient’s Appropriate laboratory tests and imaging studies can be symptoms or response to initial therapy. If adequate pain conducted to evaluate for nongynecological causes of CPP relief is obtained from NSAIDs or OCs (individually or in and, if endometriosis is present, to assess the extent of the combination), then a maintenance management regimen disease. These tests and studies are as follows: should be considered (see section H of the algorithm).
If the initial medical therapy fails to relieve the pain FERTILITY & STERILITY௡
Closer view of section E of overall algorithm shown in Figure 1: laparoscopic diagnosis and conservative treatment ofendometriosis.
Gambone. Chronic pelvic pain and endometriosis. Fertil Steril 2002. symptoms, then a trial of a second-line treatment should be directed excision, ablation, or both should be strongly con- considered (see section D of the algorithm).
sidered provided that the operator is adequately experienced.
The location and/or extent of disease in combination with the Section D: Options for Second-Line
patient’s desires regarding future fertility are important con- Treatment
siderations. Patients with dysmenorrhea who have not re- If first-line medical therapy fails, there are two therapeu- sponded to medical therapy may be offered PSN at laparot- tic options to consider. First, a trial of advanced medical omy or, if the operator is adequately experienced, via therapy should be considered (see section G of the algo- laparoscopy. Available evidence suggests that LUNA does rithm). Alternately, an operative procedure such as laparos- not benefit women with CPP associated with endometriosis.
copy or laparotomy may be considered (see section E of thealgorithm). Considerations relevant to the selection of one of Section F: Adjunctive Medical Treatment
these treatment options include the following: Adjunctive medical therapy should be provided to women after conservative surgical treatment for endometriosis and ● Several available second-line medical treatments are may consist of danazol, GnRH-a, or progestins, based on effective and are relatively free of serious complica- individual response to previous trials of medical therapy, patient preference, and other factors. There is no published ● Laparoscopy and other surgical procedures may be less evidence supporting OCs as an adjunctive medical treatment, effective than medical therapies and are reported to although a trial and continuation when effective seems rea- entail greater cost and surgical complication rates (re- ● Patient preferences, cost, effect on future fertility, and Section G: Advanced Medical Therapy
the possibility and consequences of a false presumptive Advanced medical treatment instead of surgery is recom- diagnosis should always be taken into account.
mended for women with CPP that has not responded to Section E: Operative Diagnosis and
NSAIDs or OCs or for whom these agents are contraindi- Conservative Surgical Treatment
If patients with CPP undergo diagnostic laparoscopy and Unless contraindicated, advanced medical therapy should endometriosis is identified and thought to cause or contribute begin with a 2-month trial of full-dose danazol, GnRH-a, or to the pain, conservative treatment with laparoscopically a progestin such as MPA and continued for 6 months or Gambone et al.
longer if relief is obtained. If a GnRH-a is selected, an remain significant gaps in the body of evidence available for appropriate add-back regimen should be considered (unless many important clinical problems, a situation that continues contraindicated) to minimize treatment side effects.
to make the opinions of panels of experts a necessary and When side effects or other considerations preclude a essential part of clinical decision making (84). This meth- complete trial of danazol, GnRH-a or MPA, or if all such odology combines a search for the best evidence in conjunc- agents are contraindicated, then surgical evaluation should tion with a formal opinion-based process to gain consensus when available evidence does not provide specific guidance.
Chronic pelvic pain is a common clinical complaint that If adequate pain relief is not obtained from a complete is responsible for 40% of laparoscopies and 6%–18% of trial of an advanced medical therapy, then alternative diag- hysterectomies, either alone or in combination with other noses should be considered (section B above).
indications. There is evidence that a substantial proportion of If adequate pain relief is obtained from the selected agent, women with CPP have nongynecologic causes for their then an appropriate maintenance management regimen symptoms (85) and that Յ50% have a history of current or should be initiated (section H below), keeping in mind that previous physical or sexual abuse (86 – 88). Endometriosis is pain often has multiple causes and may recur, requiring a histologic diagnosis frequently associated with pain, in- reevaluation and treatment revisions.
cluding CPP. The literature is not consistent regarding the Section H: Surveillance and Medical
link between visualized endometriosis (the basis of AFS Maintenance
staging) and CPP. Clearly, endometriosis can be asymptom-atic, and women with CPP may harbor asymptomatic endo- Maintenance, after acute treatment, should include peri- metriosis together with other causes for their symptoms. This odic monitoring for return of symptoms, continuing treat- may be one explanation for therapeutic failure or recurrence, ment with NSAIDs or OCs, or continuing treatment with including the persistence of CPP in Յ10% of women who second-line medical therapies such as danazol, GnRH-a, or have had a hysterectomy and bilateral salpingo-oopherec- tomy (89, 90). Consequently, it is incumbent on the clinician Selection of appropriate maintenance management should to consider the potential for entities other than endometriosis be based on the history of symptoms, treatment effective- ness, and patient preference, as follows: Many women with CPP have normal pelvic exams, and ● Women who obtain adequate relief from NSAIDs or many have findings consistent with endometriosis. There OCs but for whom symptoms return upon completion or have been no published clinical trials that have compared cessation of medical treatment should be maintained on directly surgical and medical therapy for CPP and endome- the therapeutic regimen that previously produced relief.
triosis. On the basis of the results of the current review, they ● Women who obtain relief from advanced medical ther- could be considered equally effective, however. Conse- apies but for whom symptoms return upon reversion to quently, the consensus panel supported the notion of primary NSAIDs or OCs should be considered for long-term medical therapy for women with CPP that is suspected to be treatment with advanced medical therapies.
related to endometriosis. Should this therapy fail, a trial of ● Women who obtain relief from laparoscopic resection advanced medical therapy with danazol, GnRH-a, or contin- and/or ablation should be considered for continuation uous progestins is considered an appropriate option without treatment with NSAIDs or OCs or with advanced med- prior laparoscopy. However, when a pelvic or adnexal mass is detected, operative evaluation or surgical exploration isrecommended because of the possibility of neoplasia.
Section I: Nonconservative Surgical Therapy
Bilateral salpingo-oophorectomy, with or without hyster- For women in whom surgery is performed, the nature of ectomy, should be reserved for women who have completed the procedure should be individualized and tailored to the their child bearing and who realize the potential impact of desires of the patient regarding future fertility, the location castration on other health parameters such as risk of osteo- and extent of disease, and the experience and expertise of the porosis, sexual dysfunction, and other menopausal issues.
surgeon. It is clear that successful surgical results may be Hysterectomy alone has little or no place in the management temporary and that the use of postoperative adjuvant medical of women who have CPP secondary to endometriosis alone.
therapy appears to reduce or delay the return of CPP. Al-though there is some evidence that presacral neurectomyprovides relief of midline pain in women with endometriosis, DISCUSSION
available evidence suggests that uterosacral ablation is not A substantial portion of current medical and surgical effective. We were unable to find evidence that adjuvant practice is primarily opinion based. Opinions underlying uterine suspension has undergone critical evaluation.
clinical decision-making are not always based on the best For women who have no desire for future fertility and currently available evidence (82, 83). Nevertheless, there who are willing to deal with the risks of surgical menopause, FERTILITY & STERILITY௡
bilateral oophorectomy, with or without hysterectomy, has lewski, M.D.; Eureka, California: Depak Stokes, M.D.; Salt Lake City, been shown to relieve symptoms, provided that endometri- Utah: Mark Stowers, M.D.; Englewood, Colorado: Eric S. Surrey, M.D.;Fullerton, California: Jerry Thanos, M.D.; Eugene, Oregon: Eldad Vered, osis is the cause of the CPP or at least is a significant M.D.; Beaumont, Texas: Ruben Victores, M.D.
Finally, we demonstrated the use of a formal consensus development process in facilitating the critical review andinterpretation of a body of evidence by a panel of practicinggynecologists.
Funding support disclosure: Partial funding was provided by an unre- This process and the participation of a large panel of stricted grant from the International Center for Postgraduate Medical Edu- practicing gynecologists differed from other consensus de- cation (ICPMED), formerly Medical Education Collaborative (MEC), an velopment processes, which often rely on a much smaller independent non-profit medical education provider. ICPMED’s program- group of academic experts, with far less geographic and ming is partially supported by TAP Pharmaceuticals. ICPMED providedlogistical and administrative support for the consensus conference and practice-setting diversity and representation. Although the evidence review. No ICPMED or TAP representatives played any substan- advanced preparation and initial formulation of consensus tive role in the development, review or reporting of the consensus statement statements were performed by a smaller executive commit- tee (CSEC), thereby limiting the breadth of opinion, sub-stantial changes were made by the larger panel during a References
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