The direct and indirect costs associated with endometriosis: a systematic literature review.

STUDY QUESTION: What is the economic burden of endometriosis? SUMMARY ANSWER: The identified studies indicate that there is a significant economic burden associated with endometriosis, as observed by both direct and indirect costs. WHAT IS KNOWN ALREADY: Two previous systematic literature reviews suggested that there were considerable direct costs associated with endometriosis and there was a general lack of measurement of indirect costs. STUDY DESIGN, SIZE, DURATION: We performed a systematic literature review. MEDLINE and EMBASE databases from 2000 to 2013 were searched. The literature search was limited to human studies of patients with endometriosis. Papers in languages other than English were excluded. PARTICIPANTS/MATERIALS, SETTING, METHODS: Studies reporting direct or indirect costs among patients with endometriosis were considered for inclusion. Direct costs included inpatient, outpatient, surgery, drug and other healthcare service cost. Indirect costs were related to absenteeism and presenteeism (lost productivity at work). MAIN RESULTS AND THE ROLE OF CHANCE: After evaluating the 1396 articles in the search results, 12 primary studies that reported direct or indirect costs associated with endometriosis were identified and included in the data extraction. Three of the studies were conducted in the USA, one study each was conducted in Austria, Belgium, Brazil, Canada, Finland, Germany and Italy, and two studies included data from 10 countries. Significant variability was observed in the reviewed studies in methodology, including data source, cost components considered and study perspective. Estimates of total direct costs ranged from $1109 per patient per year in Canada to $12 118 per patient per year in the USA. Indirect costs of endometriosis ranged from $3314 per patient per year in Austria to $15 737 per patient per year in the USA. LIMITATIONS, REASONS FOR CAUTION: The studies identified in the systematic literature review varied greatly by study methodology as well as by country owing to different healthcare systems and costs of healthcare services, which contributed to large variations in the direct and indirect cost estimates. WIDER IMPLICATIONS OF THE FINDINGS: A majority of the studies we found were published after the periods covered in the prior systematic literature reviews, which provided substantial contributions to an understanding of the economic burden of endometriosis, especially in the area of indirect costs. The long-term burden of endometriosis following diagnosis is still under-studied, which is a concern given the chronic nature of the disease and the substantial recurrence of endometriosis symptoms. STUDY FUNDING/COMPETING INTERESTS: This study was funded by AbbVie, which also develops the oral GnRH antagonist elagolix (in collaboration with Neurocrine Biosciences) for the management of endometriosis and uterine fibroids. A.M.S. is an employee of AbbVie and currently owns AbbVie stocks. H.Y., E.X.D. and C.K. are employees of Analysis Group, Inc., which has received consultancy fees from AbbVie. C.W. is a Clinical Professor at the Department Obstetrics and Gynecology at Georgetown University in Washington, DC, USA and has served in a consulting role to AbbVie for this project.

The direct and indirect costs of uterine fibroid tumors: a systematic review of the literature between 2000 and 2013.

This systematic literature review was conducted to summarize the direct and indirect costs per patient that are associated with uterine fibroid tumors in international studies. A search with predefined search terms was conducted in MEDLINE and EMBASE for studies that were published from January 2000 to November 2013. The review included primary studies that were in English and that reported either direct costs (drug costs, procedure costs, and medical service costs) or indirect costs (such as productivity loss) among patients with uterine fibroid tumors. A total of 26 studies that were identified and included in the data extraction included 19 studies in the United States, 2 studies in the Netherlands, 1 study each in Germany, China, Italy, and Canada, and 1 study reported data that were collected from 3 countries: Germany, France, and England. The studies differed substantially in perspectives that were adopted for analysis, research designs, data elements that were collected, setting, populations, and outcome measurements. Among 3 studies that reported total direct costs during the year after uterine fibroid tumor diagnosis, 2 studies reported an average of $9473 and $9319 per patient, respectively; 2 studies reported the excess costs over controls to be $6076 and $5427, respectively. The indirect costs per patient ranged from $2399-15,549, and the excess indirect cost per patient over control groups ranged from $323-4824 in the year after the diagnosis. The total costs, sum of direct and indirect costs, ranged from $11,717-25,023 per patient per year, after diagnosis or surgery among patients with uterine fibroid tumors. Compared with control subjects, the additional annual cost ranged from $2200-15,952 per patient. The results of this systematic literature review highlight the substantial direct and indirect costs that are associated with uterine fibroid tumors to health care payers and society. The large number and the variety of studies identified also emphasize the growing awareness of the significant economic impact of uterine fibroid tumors. Current gaps that were identified through this review warrant further investigation to elucidate fully the economic burden of uterine fibroid tumors, including, but not limited to, burden from the patient's perspective and the entirety of indirect costs.

Selective progesterone receptor modulator development and use in the treatment of leiomyomata and endometriosis.

Selective progesterone receptor modulators (SPRMs) represent a new class of progesterone receptor ligands. SPRMs exert clinically relevant tissue-selective progesterone agonist, antagonist, or mixed agonist/antagonist effects on various progesterone target tissues in vivo. Asoprisnil (J867) is the first SPRM to reach an advanced stage of clinical development for the treatment of symptomatic uterine fibroids and endometriosis. Asoprisnil belongs to the class of 11beta-benzaldoxime-substituted estratrienes that exhibit partial progesterone agonist/antagonist effects with high progesterone receptor specificity in animals and humans. Asoprisnil has no antiglucocorticoid activity in humans at therapeutic doses. It exhibits endometrial antiproliferative effects on the endometrium and breast in primates. Unlike progesterone antagonists, asoprisnil does not induce labor in relevant models of pregnancy and parturition. It induces amenorrhea primarily by targeting the endometrium. In human subjects with uterine fibroids, asoprisnil suppressed both the duration and intensity of uterine bleeding in a dose-dependent manner and reduced tumor volume in the absence of estrogen deprivation. In subjects with endometriosis, asoprisnil was effective in reducing nonmenstrual pain and dysmenorrhea. Asoprisnil may, therefore, provide a novel, tissue-selective approach to control endometriosis-related pain. SPRMs have the potential to become a novel treatment of uterine fibroids and endometriosis.

Return of chronic pelvic pain from endometriosis after raloxifene treatment: a randomized controlled trial.

OBJECTIVE: To evaluate whether 6 months of raloxifene was effective in treatment of chronic pelvic pain in women with endometriosis. METHODS: Women with chronic pelvic pain and no endometriosis treatment for 6 months underwent laparoscopy for excision of all lesions. Those with biopsy-proven endometriosis were randomly allocated to raloxifene (180 mg) or placebo daily. A second laparoscopy was performed at 2 years, or earlier, if pain returned. Return of pain was defined as 2 months of pain equal to or more severe than that at study entry. Menstrual cycles and adverse events were recorded. The log rank test was used to compare the time to return of pain by drug group. Analyses were done as intent-to-treat. RESULTS: A total of 127 of 158 women underwent surgery. Of these, 93 had biopsy-confirmed endometriosis and were randomly assigned to study treatment. Menstrual cycle length, pelvic pain severity, quality of life, bone mineral density, and adverse events did not differ between treatment groups. The Data Safety Monitoring Committee terminated the study early when the raloxifene group experienced pain (P=.03) and had second surgery (P=.016) significantly sooner than the placebo group. Interestingly, biopsy-proven endometriosis was not associated with return of pain (P=.6). CONCLUSION: Raloxifene significantly shortened the time to return of chronic pelvic pain. Because recurrence of endometriosis lesions did not correlate with return of pain, other factors are implicated in pelvic pain. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.cliicaltrials.gov, NCT00001848 LEVEL OF EVIDENCE: I.

Role of nonhuman primate models in the discovery and clinical development of selective progesterone receptor modulators (SPRMs).

Selective progesterone receptor modulators (SPRMs) represent a new class of progesterone receptor ligands that exert clinically relevant tissue-selective progesterone agonist, antagonist, partial, or mixed agonist/antagonist effects on various progesterone target tissues in an in vivo situation depending on the biological action studied. The SPRM asoprisnil is being studied in women with symptomatic uterine leiomyomata and endometriosis. Asoprisnil shows a high degree of uterine selectivity as compared to effects on ovulation or ovarian hormone secretion in humans. It induces amenorrhea and decreases leiomyoma volume in a dose-dependent manner in the presence of follicular phase estrogen concentrations. It also has endometrial antiproliferative effects. In pregnant animals, the myometrial, i.e. labor-inducing, effects of asoprisnil are blunted or absent. Studies in non-human primates played a key role during the preclinical development of selective progesterone receptor modulators. These studies provided the first evidence of uterus-selective effects of asoprisnil and structurally related compounds, and the rationale for clinical development of asoprisnil.

Analysis of Adherence, Persistence, and Surgery Among Endometriosis Patients Treated with Leuprolide Acetate Plus Norethindrone Acetate Add-Back Therapy.

BACKGROUND: Endometriosis affects over 10 million women in the United States. Depot leuprolide acetate (LA), a gonadotropin-releasing hormone agonist, has been used extensively for the treatment of women with endometriosis but is associated with hypoestrogenic symptoms and bone mineral density loss. The concomitant use of add-back therapies, specifically norethindrone acetate (NETA), can alleviate these adverse effects. OBJECTIVE: To compare adherence to and persistence with LA treatment and time to endometriosis-related surgery among women treated with NETA and women treated with LA plus other add-back therapies or LA only. METHODS: This retrospective analysis was conducted using Truven Health MarketScan Commercial Claims and Encounters Database. Women with a diagnosis of endometriosis (ICD-9-CM code 617.xx) who initiated LA (index date) in 2005-2011 were selected for inclusion. Additional requirements were 12 months of continuous enrollment pre- and post-index and no evidence of endometriosis-related surgeries pre-index or up to 30 days post-index; no pre-index use of estrogen or noncontraceptive hormones; and no diagnoses of uterine fibroids, malignant neoplasms, infertility, or pregnancy. Patients were characterized as using NETA; other add-back therapies (estrogens, progestins, or estrogen-progestin combinations); or no add-back therapy. Adherence to and persistence with LA were measured over the 6 months following the index date using outpatient medical and pharmacy claims. Patients were considered adherent if their proportion of days covered was greater than or equal to 0.80. Persistence was operationalized as time to discontinuation, defined as a continuous gap of > 60 days without LA on hand. Time to endometriosis-related surgery (laparotomy, laparoscopy, excision/ablation/fulguration, oophorectomy, and hysterectomy) was measured over the 12 months following the index date. Surgeries were identified from inpatient and outpatient medical claims using procedure codes. Outcomes were compared among cohorts using multivariable logistic and Cox proportional hazards regression models controlling for demographics and baseline clinical characteristics. RESULTS: The final sample included 3,114 women, with a mean age of 36.9 years. The majority of women used LA only with no add-back therapy (n = 1,963, 63.0%), while 15.1% (n = 470) used NETA, and 21.9% (N = 681) used other add-back therapies. During the 6-month follow-up, more patients in the LA plus NETA cohort were adherent to LA therapy compared with LA only (47.2% vs. 31.5%, P < 0.001), and fewer patients discontinued (37.9% vs. 59.6%, P < 0.001). Additionally, fewer patients underwent endometriosis-related surgery in the 12 months after LA initiation in the LA plus NETA cohort (12.6% vs. 16.9%, P = 0.021). In multivariable models, women who initiated LA plus NETA or LA plus other add-back therapies had a higher likelihood of being adherent to LA than LA only patients (OR = 1.91, 95% CI = 1.55-2.36 and OR = 1.95, 95% CI = 1.63-2.34) and lower likelihood of LA discontinuation (HR = 0.54, 95% CI = 0.46-0.63 and HR = 0.59, 95% CI = 0.52-0.68). NETA patients had a lower surgery rate in the 12-month post-index period compared with other add-back patients (HR = 0.68, 95% CI = 0.50-0.93) or LA only patients (HR = 0.69, 95% CI = 0.52-0.92). CONCLUSIONS: For women with endometriosis, treatment with LA and concomitant add-back therapies was associated with better adherence to and persistence with LA over the 6 months following initiation, compared with treatment with LA only. The increased adherence and persistence to LA may translate into decreased need for surgical intervention, although fewer endometriosis-related surgeries were only observed in the 12 months following LA initiation for patients using concomitant NETA add-back therapy. These results support an increased and earlier use of NETA add-back therapy among women who initiate LA. DISCLOSURES: This study was funded by AbbVie, which also markets the endometriosis drugs Lupron and Lupaneta Pack. AbbVie participated in the study design, research, data collection, analysis and interpretation, writing, review, and approval of this publication. Soliman and Castelli-Haley are employees of AbbVie and may own AbbVie stock or stock options. Bonafede and Farr are employees of Truven Health Analytics, which received a research contract to conduct this study with and on behalf of AbbVie. Winkel is a clinical professor in the Department of Obstetrics and Gynecology at Georgetown University in Washington, DC, and has served in a consulting role on research to AbbVie for this project. An earlier version of the current research was presented at the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) 20th Annual International Meeting; Philadelphia, PA; May 2015. All authors participated in data analysis and interpretation and contributed to the development of the manuscript.

Analysis of subsequent surgery rates among endometriosis patients who underwent surgery with and without concomitant leuprolide acetate therapy.

Objective To compare subsequent endometriosis-related surgery following initial laparoscopy among women treated with leuprolide acetate (LA) or other endometriosis therapies versus women who received no pharmacotherapy. Research design and methods This retrospective cohort analysis utilized MarketScan Commercial claims data. Women with endometriosis aged 18-49 who underwent laparoscopy between 1 January 2005 and 31 December 2011 were identified using diagnosis and procedures codes and were categorized into four cohorts based on claims within 90 days of laparoscopy: surgery plus adherent LA, surgery plus non-adherent LA, surgery plus other therapy, and surgery alone. Patients with proportion of days covered ≥0.80 in the 6 months after laparoscopy were considered adherent to LA. Main outcome measures Subsequent endometriosis-related surgery (laparoscopy, laparotomy or other excision/ablation/fulguration of endometriosis lesions, oophorectomy, or hysterectomy) was measured in the 6 and 12 months following initial laparoscopy. Risk of subsequent surgery was compared using multivariable Cox proportional hazards modeling. Results Most women were treated with surgery only (n = 9865); fewer were treated with LA (adherent: n = 202; non-adherent: n = 490) or other therapies (n = 230). The proportion of patients with subsequent surgery ranged from 2.0% to 10.0% during the 6 month follow-up (12 month: 9.7% to 13.5%). Adherent LA use was associated with significantly lower risk of surgery compared to surgery alone (hazard ratio [HR] = 0.31, p = 0.020) while use of other therapies was associated with significantly higher risk (HR = 1.51, p = 0.045) over the 6 month follow-up. There was no significant difference between the surgery plus non-adherent LA and surgery only cohort over 6 months (p = 0.247). The association between adherent LA and subsequent surgery was not significant over the 12 month follow-up. Conclusion Therapy with LA after laparoscopy for endometriosis was associated with lower risk of subsequent surgery at 6 months among women who were adherent to LA. Key limitations include lack of ability to capture disease severity which may have resulted in uncontrolled confounding.

Healthcare utilization and costs among women diagnosed with uterine fibroids: a longitudinal evaluation for 5 years pre- and post-diagnosis.

OBJECTIVE: To evaluate the healthcare utilization, treatments, and costs incurred by women with uterine fibroids (UF), compared to those without UF, for 5 years before and 5 years after diagnosis. RESEARCH DESIGN AND METHODS: This is a longitudinal, retrospective case-control study. A total of 84,954 women with a diagnosis of UF, along with matched controls of women without UF, were selected from the Truven Health MarketScan claims database (2000-2010). The date of diagnosis of the UF patient was assigned as the index date for both the UF patient and her matched control. MAIN OUTCOME MEASURES: Healthcare resource utilization, treatments, and costs (in 2010 USD) were evaluated annually for the 5 year periods before and after the index date. RESULTS: UF patients had more outpatient and emergency room visits than controls before diagnosis, and more inpatient, outpatient, and emergency room visits than controls after diagnosis. Annual total healthcare costs were significantly higher for patients than controls during the last 3 years pre-index and all 5 years post-index. Overall, the difference was $12,623 over 10 years, with a difference of $1435 in the 5 years pre-diagnosis and a difference of $11,188 in the 5 years post-diagnosis. The cost difference between UF patients and controls was highest in the first year post-diagnosis, reaching $6131, and the difference was even larger when comparing clinically symptomatic UF patients to controls. The use of medications and surgical procedures related to UF peaked in the year post-diagnosis, with 39% of patients receiving a surgical treatment within the year. KEY LIMITATIONS: UF patients included in the study did not include undiagnosed and potentially asymptomatic UF patients; the impact of disease severity on the costs of UF patients was not evaluated. CONCLUSIONS: Patients with UF incurred significantly higher healthcare utilization and costs than those without UF, both pre- and post-diagnosis.

Healthcare utilization and costs in women diagnosed with endometriosis before and after diagnosis: a longitudinal analysis of claims databases.

OBJECTIVE: To assess healthcare resource utilization and costs during the 5 years before and 5 years after diagnosis among women with endometriosis, in comparison with women without endometriosis. DESIGN: Longitudinal, retrospective, case-control study. SETTING: None. PATIENT(S): A total of 37,570 matched pairs of women with and without (controls) endometriosis were identified from the Truven Health MarketScan claims database (2000-2010). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Annual healthcare resource utilization and costs (in 2010 US dollars) were evaluated for the 5 years before and 5 years after diagnosis. RESULT(S): Mean patient age at index (first diagnosis) date was 36.4 years for endometriosis patients and controls. Endometriosis patients had a higher utilization of outpatient and emergency room services during each pre- and postindex year, and a higher utilization of inpatient services during the last preindex year and all 5 postindex years. Total costs were highest in the first postindex year for endometriosis patients, reaching $13,199, compared with $3,747 for controls. Annual costs were significantly higher for patients than controls during each pre- and postindex year; overall, the cost difference was $26,305 over 10 years: $7,028 in the 5 years before diagnosis and $19,277 in the 5 years after diagnosis. CONCLUSION(S): Endometriosis poses a significantly high economic burden, both before and after diagnosis. The highest resource utilization and costs experienced by endometriosis patients occur in the first year after diagnosis.

Evaluation and management of women with endometriosis.

Endometriosis is a condition that often leads to a variety of symptoms that range from pain complaints to infertility. Endometriosis is also found in women who are asymptomatic. The diagnosis of endometriosis can be made clinically with reliability similar to that of one made surgically. Medical treatment options are effective, as are surgical treatment options. Complications associated with surgery, however, push the balance in favor of medical therapy whenever possible. Based on the body of evidence available at present, women with endometriosis-related complaints should be treated with a first-line medical therapy. If that fails, a second-line medical therapy is warranted under most conditions. Laparoscopic surgery should be reserved for patients in whom second-line medical therapy has failed or is contraindicated by desire to conceive immediately or as soon as possible.

Intrauterine head entrapment of a second twin by a uterine synechia.

BACKGROUND: Fetal head entrapment during delivery is a rare occurrence in modern obstetrics. We present a case of intrauterine head entrapment of a second twin by a uterine synechia diagnosed by ultrasound and subsequent complications that occurred. CASE: A woman with a twin intrauterine pregnancy presented at 19 weeks for evaluation of a shortened cervix. Ultrasound examination demonstrated fetal head entrapment of twin B by a uterine synechia, as well as intrauterine growth restriction (IUGR). The patient experienced preterm premature rupture of membranes at 24 weeks' gestation and underwent a cesarean delivery for a nonreassuring fetal heart rate tracing of twin B, with findings of a constricting band of fibrous tissue around the neck of twin B. CONCLUSION: Uterine synechia might cause intrauterine head entrapment and IUGR.

Dysmenorrhea after bilateral tubal ligation: a case of retrograde menstruation.

BACKGROUND: Endometriosis, arising de novo, is believed to be uncommon in women who have undergone bilateral tubal ligation because the occluded tube prevents outflow of blood and menses. CASE: A woman 10-year status-post bilateral tubal ligation suffered from dysmenorrhea and menorrhagia that began within 1 year after sterilization. At the time of bilateral tubal ligation, no endometriosis was observed. A recent magnetic resonance imaging scan showed no pelvic abnormalities, and the patient underwent a diagnostic laparoscopy in anticipation of finding endometriosis, yet none was found. At laparoscopy performed on day 3 of her menstrual cycle, the proximal segments of her occluded fallopian tubes were dilated with blood. As this was the only abnormality found, we postulated that her dysmenorrhea might be related to the dilated proximal tubal stumps. We evacuated the bloody fluid and occluded the proximal tube at the cornua with Filshie clips. One year after surgery, the patient remains asymptomatic. CONCLUSION: This case is unique because bilateral tubal ligation combined with retrograde menstrual flow appears to have caused dysmenorrhea. Women who have undergone tubal ligation and who have dysmenorrhea may benefit from a diagnostic laparoscopy during menstruation to evaluate the possibility of retrograde menstruation dilating the proximal tubal stumps.

Urine vascular endothelial growth factor-A is not a useful marker for endometriosis.

OBJECTIVE: To determine whether urine VEGF is elevated in women with endometriosis. DESIGN: Prospective observational study. SETTING: Tertiary care government and private hospitals. PATIENT(S): During laparoscopy for pelvic pain or infertility, urine was collected and possible endometriosis lesions were excised. Of 62 women, 40 had histology-proven endometriosis and 22 had no histological proof of the disease. INTERVENTION: None. MAIN OUTCOME MEASURE(S): Urine VEGF-A(121, 165) was measured and compared in women with and without biopsy-proven endometriosis. RESULT(S): Urine VEGF levels corrected for creatinine excretion were similar in women with (83.6 +/- 11.3 pg/mg Cr) and without (88.5 +/- 10.4 pg/mg Cr) endometriosis (P =.77). The frequency distribution of urine VEGF measurements for women with and without endometriosis was similar. No significant difference was noted in urine VEGF levels when comparing endometriosis stages or in those with endometriomas compared to controls. Urine VEGF did not vary significantly over the menstrual cycle or between groups by cycle phase. No cutoff point discriminated individuals with and without the condition. CONCLUSION(S): It is unlikely that urine VEGF-A(121, 165), as measured in this study, will be a useful non-invasive marker for endometriosis.

Consensus statement for the management of chronic pelvic pain and endometriosis: proceedings of an expert-panel consensus process.

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 >50 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.

Location, color, size, depth, and volume may predict endometriosis in lesions resected at surgery.

OBJECTIVE: To correlate the diagnosis of endometriosis in lesions excised at laparoscopy with pathologic diagnosis. DESIGN: Prospective study. SETTING: U.S. government research hospital. PATIENT(S): Women with chronic pelvic pain thought to be due to endometriosis. INTERVENTION(S): Excision of lesions suspicious for endometriosis. MAIN OUTCOME MEASURE(S): Histologic examination of lesions for color, width, depth, and location of endometriosis. Lesion colors were grouped as black, red, white, mixed color, or endometriomas. RESULT(S): Sixty-five women with a surgical diagnosis of endometriosis had minimal (n = 22), mild (n = 25), moderate (n = 9), or severe disease (n = 9) according to the revised American Fertility Society classification. Endometriosis was confirmed in all but seven patients with minimal and one with severe disease. Twelve other patients did not have endometriosis. Of 314 lesions excised, 189 (61%) were endometriotic. Black or red lesions were less often histologically confirmed to be endometriosis than were white lesions, mixed-color lesions or endometriomas. Lesions > 5 mm wide or deep were more likely to be endometriosis than were narrower or shallower implants. Endometriomas deeper than 1 cm were histologically confirmed to be endometriosis, and 50% of peritoneal windows contained endometriosis. CONCLUSION(S): White lesions, mixed-color lesions, endometriomas, and larger lesions by depth or width were more likely to be histologically confirmed endometriosis than were smaller, black, or red lesions.

Diagnostic accuracy of laparoscopy, magnetic resonance imaging, and histopathologic examination for the detection of endometriosis.

OBJECTIVE: To evaluate the utility of fat-suppressed magnetic resonance imaging (MRI) in the diagnosis of endometriosis. DESIGN: A prospective clinical trial. SETTING: A government research hospital. PATIENT(S): Forty-eight women with pelvic pain. INTERVENTION(S): Magnetic resonance imaging followed by surgical excision and pathologic diagnosis of endometriosis. MAIN OUTCOME MEASURE(S): Presence and extent of endometriosis suggested by preoperative MRIs compared with surgical inspection and biopsy. RESULT(S): A preoperative MRI in 46 women detected fewer endometriosis lesions than histopathology or laparoscopy (78 vs. 101 vs. 150). Few MRI lesions correlated with those identified by laparoscopy (50 of 150) or pathology (38 of 101). Of 42 women with surgically diagnosed endometriosis, 28 had at least one corresponding abnormality on MRI, 5 had abnormalities that didn't correlate with surgical findings, and 9 had normal MRIs. The sensitivity of MRI in detecting biopsy-proven endometriosis for any woman was 69% (25 of 36), and the specificity was 75%. CONCLUSION(S): Although MRI identifies fewer areas of endometriosis than seen at surgery, it suggested endometriosis in 75% of those with at least mild disease. Only 67% of lesions identified at surgery contained histologic evidence of endometriosis.

Struma ovarii coincident with Hashimoto's thyroiditis: an unusual cause of hyperthyroidism.

OBJECTIVE: To report the identification of struma ovarii in a patient with a history of struma ovarii and new hyperthyroidism. DESIGN: Case report. SETTING: Academic research hospital. PATIENT(S): A woman with hyperthyroidism who has struma ovarii coincident with Hashimoto's thyroiditis. INTERVENTION(S): Laparoscopic salpingo-oophorectomy. MAIN OUTCOME MEASURE(S): Measurement of thyroid hormone parameters before and after surgery. RESULT(S): After removal of the second struma ovarii, hyperthyroidism resolved. CONCLUSION(S): In a patient with two different causes of abnormal thyroid function, it is important to seek an encompassing clinical scenario.

A randomized, controlled trial of asoprisnil, a novel selective progesterone receptor modulator, in women with uterine leiomyomata.

OBJECTIVE: To determine efficacy and safety of asoprisnil in patients with leiomyomata. DESIGN: Phase 2, multicenter, prospective, randomized, double-blind, placebo-controlled, parallel-group study. SETTING: Twenty-eight sites in the United States and 1 in Canada. PATIENT(S): One hundred twenty-nine women with leiomyomata. INTERVENTION(S): Asoprisnil (5, 10, or 25 mg) or placebo orally daily for 12 weeks. MAIN OUTCOME MEASURE(S): Uterine bleeding changes by using daily bleeding diaries, hemoglobin concentrations, dominant leiomyoma and uterus volume measured sonographically, patient-reported symptoms related to bloating and pelvic pressure, endometrial thickness and morphology, hormonal parameters, and standard safety measures. RESULT(S): Asoprisnil suppressed uterine bleeding in 28%, 64%, and 83% of subjects at 5, 10, and 25 mg, respectively, and reduced leiomyoma and uterine volumes. Median percentage decrease from baseline in leiomyoma volume was statistically significant at 25 mg compared with placebo after 4 and 8 weeks of treatment; by week 12, leiomyoma volume was reduced by 36%. There was a significant reduction in bloating with the two highest doses and in pelvic pressure with 25 mg by week 12. Asoprisnil was associated with follicular-phase estrogen concentration and minimal hypoestrogenic symptoms. CONCLUSION(S): After 12-week treatment, asoprisnil controlled uterine bleeding while reducing leiomyoma volume and the associated pressure symptoms. Asoprisnil was well tolerated.

Adhesion formation after laparoscopic excision of endometriosis and lysis of adhesions.

OBJECTIVE: To evaluate adhesion reformation after laparoscopic excision of endometriosis and adhesiolysis in women with chronic pelvic pain. DESIGN: Prospective clinical trial. SETTING: University hospital. PATIENT(S): Thirty-eight women with endometriosis and chronic pelvic pain. INTERVENTION(S): A primary and second-look laparoscopy with adhesiolysis and excision of endometriotic lesions with a neodymium-yttrium argon garnet surgical laser technologies (SLT) contact laser. MAIN OUTCOME MEASURE(S): Adhesion formation and character (thin, thin and thick, or thick). Location of adhesions at a first laparoscopy was compared with de novo or reformation of adhesions and the location of adhesions at a second surgery. RESULT(S): Adhesions or adhesions combined with endometriotic lesions were significantly more likely to reform at second surgery compared with sites having only an endometriosis lesion. Thick adhesions were associated with a significantly increased likelihood of an adhesion reforming, compared with thin adhesions or thin and thick adhesions. Lesions or adhesions involving the ovary were more likely to be associated with adhesions at a subsequent surgery, compared with lesions in the adjacent ovarian fossa or fallopian tube. CONCLUSION(S): Most patients developed adhesions after radical surgical excision of endometriosis for pelvic pain. The high incidence of adhesion formation after surgery for endometriosis underscores the importance of optimizing surgical techniques to potentially reduce adhesion formation.

Gonadotropin-releasing hormone agonists.

Preview Gonadotropin-releasing hormone (GnRH) agonists will have a significant impact on the practice of medicine in the 1990s. These agents will likely be given to increasing numbers of patients, and primary care physicians themselves may wish to prescribe the drugs when appropriate. This article describes the use of GnRH agonists in the treatment of endometriosis, advanced prostate cancer, and precocious puberty.