Laparoscopically confirmed endometriosis and anti-Müllerian hormone levels: Findings from the Nurses' Health Study II.

OBJECTIVE: Anti-Müllerian hormone is a reliable measure of ovarian reserve associated with menopause timing and fertility. Previous studies have observed that individuals with endometriosis have lower anti-Müllerian hormone levels than those without. However, sample sizes have been small and information is limited regarding the long-term influence of endometriosis on anti-Müllerian hormone levels among the general population, which may have important implications for menopause timing and chronic disease risk. METHODS: Among 1961 premenopausal women in the Nurses' Health Study II who provided a blood sample and had not been pregnant in the last 6 months, we used generalized linear models to determine the association between laparoscopically-confirmed endometriosis and log-transformed plasma anti-Müllerian hormone level, adjusted for age (continuous and squared) and other potential confounding variables. RESULTS: Participants were on average 40 years old (interquartile range 37-42 years) at blood draw. Women with endometriosis diagnosed prior to blood draw (n = 119) had a lower mean anti-Müllerian hormone level (1.6 ng/mL [SD = 2.3]) than women without known endometriosis (n = 1842) (2.8 ng/mL [SD = 3.0]). In multivariable adjusted models, women with endometriosis had 29.6 % lower anti-Müllerian hormone levels (95 % CI: -45.4, -9.2 %) than women without. This association was greater among women with a body mass index of 25 kg/m2 or more (percent difference: -44.0 % (-63.7, -13.8)), compared to those with a body mass index of under 25 kg/m2 (percent difference: -19.8 % (-41.7, 10.4)), but did not vary by parity or infertility history. CONCLUSIONS: Lower anti-Müllerian hormone levels in women with endometriosis may be one mechanism through which endometriosis influences risk of infertility, younger age at menopause, and cardiovascular disease.

Hysterectomy With and Without Oophorectomy, Tubal Ligation, and Risk of Cardiovascular Disease in the Nurses' Health Study II.

Background: Hysterectomy, oophorectomy, and tubal ligation are common surgical procedures. The literature regarding cardiovascular disease (CVD) risk after these surgeries has focused on oophorectomy with limited research on hysterectomy or tubal ligation. Materials and Methods: Participants in the Nurses' Health Study II (n = 116,429) were followed from 1989 to 2017. Self-reported gynecologic surgery was categorized as follows: no surgery, hysterectomy alone, hysterectomy with unilateral oophorectomy, and hysterectomy with bilateral oophorectomy. We separately investigated tubal ligation alone. The primary outcome was CVD based on medical-record confirmed fatal and nonfatal myocardial infarction, fatal coronary heart disease, or fatal and nonfatal stroke. Our secondary outcome expanded CVD to include coronary revascularization (coronary artery bypass graft surgery, angioplasty, stent placement). Cox proportional hazard models were used to calculate hazard ratios (HR) and 95% confidence intervals (CIs) and were adjusted a priori for confounding factors. We investigated differences by age at surgery (≤50, >50) and menopausal hormone therapy usage. Results: At baseline, participants were on average, 34 years old. During 2,899,787 person-years, we observed 1,864 cases of CVD. Hysterectomy in combination with any oophorectomy was associated with a greater risk of CVD in multivariable-adjusted models (HR hysterectomy with unilateral oophorectomy:1.40 [95% CI: 1.08-1.82]; HR hysterectomy with bilateral oophorectomy:1.27 [1.07-1.51]). Hysterectomy alone, hysterectomy with oophorectomy, and tubal ligation were also associated with an increased risk of combined CVD and coronary revascularization (HR hysterectomy alone: 1.19 [95% CI: 1.02-1.39]; HR hysterectomy with unilateral oophorectomy: 1.29 [1.01-1.64]; HR hysterectomy with bilateral oophorectomy: 1.22 [1.04-1.43]; HR tubal ligation: 1.16 [1.06-1.28]). The association between hysterectomy/oophorectomy and CVD and coronary revascularization risk varied by age at gynecologic surgery, with the strongest association among women who had surgery before age 50 years. Conclusion: Our findings suggest that hysterectomy, alone or in combination with oophorectomy, as well as tubal ligation, may be associated with an increased risk of CVD and coronary revascularization. These findings extend previous research finding that oophorectomy is associated with CVD.

Laparoscopically Confirmed Endometriosis and Risk of Incident Stroke: A Prospective Cohort Study.

BACKGROUND: Prior research suggests that women with endometriosis are at greater risk of coronary heart disease. Therefore, our objective was to prospectively investigate the association between laparoscopically confirmed endometriosis and risk of incident stroke during 28 years of follow-up. METHODS: Participants in the NHSII cohort study (Nurses' Health Study II) were followed from 1989 when they were between the ages of 25 to 42 until 2017 for development of incident stroke (ischemic and hemorrhagic). Cox proportional hazard models were used to calculate hazard ratios and 95% CI, with adjustment for potential confounding variables (alcohol intake, body mass index at age 18, current body mass index, age at menarche, menstrual cycle pattern in adolescence, current menstrual cycle pattern, parity, oral contraceptive use history, smoking history, diet quality, physical activity, NSAID use, aspirin use, race/ethnicity, and income). We estimated the proportion of the total association mediated by history of hypertension, hypercholesterolemia, hysterectomy/oophorectomy, and hormone therapy. We also tested for effect modification by age (<50, ≥50 years), infertility history, body mass index (<25, ≥25 kg/m2), and menopausal status. RESULTS: We documented 893 incident cases of stroke during 2 770 152 person-years of follow-up. Women with laparoscopically confirmed endometriosis had a 34% greater risk of stroke in multivariable-adjusted models (hazard ratio, 1.34 [95% CI, 1.10-1.62]), compared to those without a history of endometriosis. Of the total association of endometriosis with risk of stroke, the largest proportion was attributed to hysterectomy/oophorectomy (39% mediated [95% CI, 14%-71%]) and hormone therapy (16% mediated [95% CI, 5%-40%]). We observed no differences in the relationship between endometriosis and stroke by age, infertility history, body mass index, or menopausal status. CONCLUSIONS: We observed that women with endometriosis were at elevated risk of stroke. Women and their health care providers should be aware of endometriosis history, maximize primary cardiovascular prevention, and discuss signs and symptoms of cardiovascular disease.

Recreational and residential sun exposure and risk of endometriosis: a prospective cohort study.

STUDY QUESTION: Is recreational and residential sun exposure associated with risk of endometriosis? SUMMARY ANSWER: Tanning bed use in early adulthood, sunscreen use and history of sunburns were associated with a greater risk of endometriosis; however, higher residential UV exposure was associated with a lower endometriosis risk. WHAT IS KNOWN ALREADY: Previous research has reported an association between endometriosis and skin cancer, with evidence of shared risk factors between the two diseases. We investigated the potential associations between ultraviolet radiation and endometriosis risk. STUDY DESIGN, SIZE, DURATION: The Nurses' Health Study II is a prospective cohort of 116 429 female US nurses aged 25-42 years at enrolment in 1989. Participants completed self-administered biennial questionnaires through June 2015. PARTICIPANTS/MATERIALS, SETTINGS, METHODS: We investigated self-reported measures of recreational sun-exposure and geocoded residential UV exposure in childhood and adulthood in relation to risk of laparoscopically confirmed endometriosis among premenopausal white women. We used Cox proportional hazards models to calculate hazard ratios (HRs) and 95% CIs. MAIN RESULTS AND THE ROLE OF CHANCE: During follow-up, 4791 incident cases of laparoscopically confirmed endometriosis were reported among 1 252  248 person-years. Tanning bed use during high school/college (≥6 times per year vs. never use: HR = 1.19, 95% CI = 1.01-1.40; Ptrend = 0.04) and at ages 25-35 (HR = 1.24, 95% CI = 1.12-1.39; Ptrend ≤ 0.0001), number of sunburns during adolescence (Ptrend = 0.03) and percentage of time using sunscreen in adulthood (Ptrend = 0.002) were positively associated with risk of endometriosis. In contrast, residential UV level at birth (highest vs. lowest quintile: HR = 0.81, 95% CI = 0.72-0.92; Ptrend = 0.0001), at age 15 (HR = 0.79, 95% CI = 0.70-0.88; Ptrend ≤ 0.0001) and at age 30 (HR = 0.90, 95% CI = 0.82-0.99; Ptrend = 0.21) were associated with a decreased risk of endometriosis. LIMITATIONS, REASONS FOR CAUTION: Self-reported endometriosis diagnosis may be prone to misclassification; however, we restricted our definition to laparoscopically confirmed endometriosis, which has been shown to have high validity compared to medical records. WIDER IMPLICATIONS OF THE FINDINGS: Our results suggest that tanning bed use in early adulthood increases endometriosis risk, potentially through a harmful effect of ultraviolet A wavelengths, and that residential UV exposure reduces risk, possibly via optimal vitamin D synthesis. These findings should be investigated further to enhance our understanding of endometriosis aetiology. STUDY FUNDING/COMPETING INTEREST(S): This project was supported by NICHD grants HD48544 and HD52473, HD57210, NIH grant CA50385, CA176726. M.K. was supported by a Marie Curie International Outgoing Fellowship within the 7th European Community Framework Programme (#PIOF-GA-2011-302078) and is grateful to the Philippe Foundation and the Bettencourt-Schueller Foundation for their financial support. H.R.H. is supported by the National Cancer Institute, National Institutes of Health (K22 CA193860). The authors have nothing to disclose. TRIAL REGISTRATION NUMBER: N/A.

A prospective study of endometriosis and risk of type 2 diabetes.

AIMS/HYPOTHESIS: The objective of this study was to investigate the association between laparoscopically confirmed endometriosis and risk of type 2 diabetes. METHODS: We used data from the Nurses' Health Study II, a prospective cohort of female nurses followed for >25 years (N = 112,037). We used Cox proportional hazards models to estimate the HRs and 95% CIs of incident, confirmed type 2 diabetes (n = 8496 participants) adjusted a priori for confounding factors. We additionally investigated differences in the relationship between endometriosis and type 2 diabetes by age (<50 or ≥50 years), BMI (<30 or ≥30 kg/m2), infertility history, menopausal status and history of gestational diabetes mellitus (GDM; restricted to parous women). RESULTS: We saw no association between laparoscopically confirmed endometriosis and risk of type 2 diabetes in multivariable confounder-adjusted models (HR 1.06 [95% CI 0.98, 1.13]) or models accounting for potential mediating factors (HR 0.94 [95% CI 0.87, 1.00]). However, we observed modest differences in the association between endometriosis and type 2 diabetes by BMI group, history of infertility and history of GDM. Among non-obese women (HR 1.17 [95% CI 1.02, 1.35]), women who never experienced infertility (HR 1.14 [95% CI 1.04, 1.25]) and women who never experienced GDM (HR 1.11 [95% CI 1.01, 1.22]), endometriosis was associated with greater risk of type 2 diabetes. CONCLUSIONS/INTERPRETATION: Overall, women with endometriosis were not at increased risk of type 2 diabetes. However, among subgroups at low risk for type 2 diabetes (i.e. non-obese women and women with no prior history of infertility or GDM), endometriosis was associated with a modest increased risk of type 2 diabetes.