Objective: Current estimates of endometriosis prevalence and incidence are highly variable, leading to uncertainty regarding true endometriosis frequency or validity of quantified changes over time. We present a comprehensive review of the prevalence, incidence, and stage of endometriosis worldwide as reported over the past 30 years. Data Sources: We conducted a systematic search of observational studies using the PubMed, Web of Science, EMBASE, and CINAHL databases to identify research papers published in English between January 1989 and June 2019. Search terminologies were limited to titles containing endometriosis and prevalence or incidence, or epidemiology, or frequency, or occurrence, or statistics. Methods of Study Selection: Two independent reviewers screened abstracts for study eligibility, and data from included studies were abstracted. Tabulation, Integration, and Results: Overall, 69 studies describing the prevalence and/or incidence of endometriosis met the inclusion criteria. Among these, 26 studies involved general population samples, 17 of which were from regional/ national hospitals or insurance claims systems. The other 43 studies were conducted in single clinic or hospital settings. Prevalence estimates for endometriosis widely varied from 0.2% to 71.4% depending on the population sampled. The prevalence reported in general population studies ranged from 0.7% to 8.6%, whereas that reported in single clinic-or hospitalbased studies ranged from 0.2% to 71.4%. When defined by indications for diagnosis, endometriosis prevalence ranged from 15.4% to 71.4% among women with chronic pelvic pain, 9.0% to 68.0% among women presenting with infertility, and 3.7% to 43.3% among women undergoing tubal sterilization. A meta-regression was conducted with year as the predictor of prevalence. No trend across time was observed among "general population in country/region" studies (b = 0.04, p = .12) or among "single hospital or clinic" studies (b = ˗0.02, p = .34); however, a decrease over time was observed among general population studies abstracted from health systems or insurance systems (b = À0.10, p = .005). Conclusion:As with all human studies, population sampling and study design matter. Heterogeneity of inclusion and diagnostic criteria and selection bias overwhelmingly account for variability in endometriosis prevalence estimated across the literature. Thus, it is difficult to conclude if the lack of observed change in frequency and distribution of endometriosis over the past 30 years is valid.
IMPORTANCEEarly natural menopause (ENM) has been associated with reduced reproductive span, cardiovascular disease risk, and early mortality. The potential adverse implications of endometrioma surgery for ovarian reserve are known, yet the association of endometriosis with menopausal timing remains understudied. OBJECTIVE To investigate the association between endometriosis and risk for ENM. DESIGN, SETTING, AND PARTICIPANTS This large, population-based cohort study analyzed data from the Nurses' Health Study II cohort questionnaires from the 1989 to 2015 questionnaire cycles. The sample included premenopausal women aged 25 to 42 years at baseline or enrollment in 1989. Cumulative follow-up rate was greater than 90%, and participants continued follow-up until the onset of ENM, age 45 years, hysterectomy, oophorectomy, cancer diagnosis, death, loss to follow-up, or end of follow-up in May 2017, whichever occurred first. Data analyses were conducted from October 26, 2020, to April 27, 2021. EXPOSURES Endometriosis diagnosis status was queried in the biennial questionnaires, with participants reporting physician diagnosis and whether the diagnosis was laparoscopically confirmed. MAIN OUTCOMES AND MEASURES Natural menopause before age 45 years. Menopause status was assessed every 2 years. RESULTSThe study included 106 633 premenopausal women with a mean (SD) age of 34.8 (4.3) years at baseline, of whom 3921 reported a laparoscopically confirmed endometriosis diagnosis.During 1 508 462 person-years of follow-up, 6640 participants reported being diagnosed with endometriosis, 99 993 never reported endometriosis, and 2542 reported experiencing ENM. In the age-and calendar time-adjusted model, laparoscopically confirmed endometriosis was associated with a 50% greater risk for ENM (hazard ratio [HR], 1.51; 95% CI, 1.30-1.74). A similar risk was observed after adjusting for race and ethnicity and time-varying anthropometric and behavioral factors (HR, 1.46; 95% CI, 1.26-1.69). With additional adjustment for reproductive factors, the HR of ENM was attenuated but significant (HR, 1.28; 95% CI, 1.10-1.48). A greater risk of ENM was observed among women who were nulliparous after stratifying by parity (nulliparous vs parous: HR, 1.46 [95% CI, 1.15-1.86] vs 1.14 [95% CI, 0.94-1.39]; P for heterogeneity = .05) or who never used oral contraceptives when stratifying by oral contraceptive use (never vs ever: HR, 2.03 [95% CI, 1.34-3.06] vs 1.20 [95% CI, 1.02-1.42]; P for heterogeneity = .02). No significant differences were observed in the association between endometriosis and ENM when stratifying by body mass index (calculated as weight in kilograms divided by height in meters squared; <25 vs Ն25: HR, 1.20 [95% CI, 0.99-1.45] vs 1.43 [95% CI, 1.11-1.83; P for heterogeneity = .34), cigarette smoking status (never vs (continued) Key Points Question Is there an association between endometriosis and early natural menopause? Findings In this cohort study of 106 633 premenopausal women, a statistically significant association was found b...
Few studies have assessed endogenous steroid hormone levels and subsequent endometriosis diagnosis. We prospectively evaluated premenopausal plasma sex hormone levels and the risk of laparoscopically-confirmed endometriosis in a nested case-control study within the Nurses’ Health Study II. Between blood collection (1996-1999) and 2009, we ascertained 446 women with incident endometriosis and matched them to 878 controls through risk-set sampling. We conducted multivariable conditional logistic regression accounting for matching and confounders to estimate relative risks (RR) and 95% confidence intervals (CI). Women with greater early follicular total or free estradiol levels had a non-linear increased risk of endometriosis (early follicular total estradiol: 2nd quartile vs 1st, RR=2.23(CI=1.44-3.47); 3rd quartile, RR=1.83(CI=1.16-2.88); 4th quartile, RR=1.68(CI=1.05-2.68); early follicular free estradiol: 2nd quartile vs 1st, RR=1.63(CI=1.05-2.54); 3rd quartile, RR=2.02(CI=1.31-3.12); 4th quartile, RR=1.04(CI=0.66-1.65)). Free testosterone assessed in quartile categories was not associated with endometriosis, although a threshold effect was observed with a positive association among women in the top 2% of free testosterone levels. Mid-luteal total and free estradiol, follicular and luteal estrone, total testosterone, progesterone, and sex hormone binding globulin levels were not associated with endometriosis risk. These results support the role of sex steroids in endometriosis etiology, although the relationships suggest complex threshold effects.
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