Dataset Information

Menstrual Cycle Characteristics in Adolescence and Early Adulthood Are Associated With Risk of Early Natural Menopause.

ABSTRACT:

Context

Early natural menopause (i.e., before age 45 years) is associated with increased risk of adverse outcomes. Associations of earlier menopause with younger age at menarche and short and/or regular cycle length are suggested, but study findings are inconsistent and few address early menopause risk.

Objective

To evaluate the relationship between menstrual cycle characteristics in early life with incident early natural menopause.

Design

The prospective Nurses' Health Study 2 (1989 to 2011).

Setting and participants

Women ages 25 to 42 years and premenopausal in 1989 (N = 108,811).

Main outcome measure(s)

Risk of early natural menopause not due to surgery, radiation, or chemotherapy (n = 2794) was evaluated with Cox proportional hazards models. Anti-Müllerian hormone (AMH) levels were considered in a nested case-control sample (n = 820).

Results

In adjusted models, risk was associated with earlier age at menarche (P for trend = 0.05), shorter (P for trend < 0.0001), and more-regular cycles (P for < 0.0001). The hazard ratio (HR) for women with age at menarche ?9 (vs. 12) years was 1.28 (95% CI, 0.99 to 1.67). Women reporting usual menstrual cycle lengths <25 days at ages 18 to 22 years had substantially higher risk of early menopause (HR, 1.70; 95% CI, 1.47 to 1.96) than women with 26- to 31-day cycles, whereas women with ?40 day cycles had lower risk (HR, 0.44; 95% CI, 0.34 to 0.58). Women with irregular cycle length had lower risk compared with women with regular cycles (HR, 0.51; 95% CI, 0.43 to 0.60). Associations with AMH concentrations among the nested case-control subset were consistent with these findings.

Conclusion

Results from this large prospective study of early menopause suggest an influence of accelerated oocyte depletion on risk and may help clarify the etiology of early menopause.

SUBMITTER: Whitcomb BW

PROVIDER: S-EPMC6179161 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Publications

Menstrual Cycle Characteristics in Adolescence and Early Adulthood Are Associated With Risk of Early Natural Menopause.

Whitcomb Brian W BW Purdue-Smithe Alexandra A Hankinson Susan E SE Manson JoAnn E JE Rosner Bernard A BA Bertone-Johnson Elizabeth R ER

The Journal of clinical endocrinology and metabolism 20181001 10

<h4>Context</h4>Early natural menopause (i.e., before age 45 years) is associated with increased risk of adverse outcomes. Associations of earlier menopause with younger age at menarche and short and/or regular cycle length are suggested, but study findings are inconsistent and few address early menopause risk.<h4>Objective</h4>To evaluate the relationship between menstrual cycle characteristics in early life with incident early natural menopause.<h4>Design</h4>The prospective Nurses' Health Stu ...[more]

PMID: 30060103

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Project description:Study questionWhat is the association of oral contraceptives (OCs) and tubal ligation (TL) with early natural menopause?Summary answerWe did not observe an association of OC use with risk of early natural menopause; however, TL was associated with a modestly higher risk.What is known alreadyOCs manipulate hormone levels, prevent ovulation, and may modify the rate of follicular atresia, while TL may disrupt the blood supply to the ovaries. These mechanisms may be associated with risk of early menopause, a condition associated with increased risk of cardiovascular disease and other adverse health outcomes.Study design, size, durationWe examined the association of OC use and TL with natural menopause before the age of 45 years in a population-based study within the prospective Nurses' Health Study II (NHSII) cohort. Participants were followed from 1989 to 2017 and response rates were 85-90% for each cycle.Participants/materials, setting, methodsParticipants included 106 633 NHSII members who were premenopausal and aged 25-42 years at baseline. Use, duration and type of OC, and TL were measured at baseline and every 2 years. Menopause status and age were assessed every 2 years. Follow-up continued until early menopause, age 45 years, hysterectomy, oophorectomy, death, cancer diagnosis, or loss to follow-up. We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% CIs adjusted for lifestyle, dietary, and reproductive factors.Main results and the role of chanceOver 1.6 million person-years, 2579 members of the analytic cohort experienced early natural menopause. In multivariable models, the duration, timing, and type of OC use were not associated with risk of early menopause. For example, compared with women who never used OCs, those reporting 120+ months of OC use had an HR for early menopause of 1.01 (95% CI, 0.87-1.17; P for trend=0.71). TL was associated with increased risk of early menopause (HR = 1.17, 95% CI, 1.06-1.28).Limitations, reasons for cautionOur study population is homogenous with respect to race and ethnicity. Additional evaluation of these relations in more diverse populations is important.Wider implications of the findingsTo our knowledge, this is the largest study examining the association of OC use and TL with early natural menopause to date. While TL was associated with a modest higher risk of early menopause, our findings do not support any material hazard or benefit for the use of OCs.Study funding/competing interest(s)The study was sponsored by UO1CA176726 and R01HD078517 from the National Institutes of Health and Department of Health and Human Services. The work was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The authors have no competing interests to report.Trial registration numberN/A.

Project description:BackgroundEarly natural menopause, the cessation of ovarian function before age 45 y, is positively associated with cardiovascular disease and other conditions. Dietary vitamin D intake has been inversely associated with early menopause; however, no previous studies have evaluated risk with regard to plasma 25-hydroxyvitamin D [25(OH)D] concentrations.ObjectiveWe prospectively evaluated associations of total and free 25(OH)D and vitamin D-binding protein (VDBP) concentrations and the risk of early menopause in a case-control study nested within the Nurses' Health Study II (NHS2). We also considered associations of 25(OH)D and VDBP with anti-Müllerian hormone (AMH) concentrations.MethodsThe NHS2 is a prospective study in 116,430 nurses, aged 25-42 y at baseline (1989). Premenopausal plasma blood samples were collected between 1996 and 1999, from which total 25(OH)D and VDBP concentrations were measured and free 25(OH)D concentrations were calculated. Cases experienced menopause between blood collection and age 45 y (n = 328) and were matched 1:1 by age and other factors to controls who experienced menopause after age 48 y (n = 328). Conditional logistic regression models were used to estimate ORs and 95% CIs for early menopause according to each biomarker. Generalized linear models were used to estimate AMH geometric means according to each biomarker.ResultsAfter adjusting for smoking and other factors, total and free 25(OH)D were not associated with early menopause. Quartile 4 compared with quartile 1 ORs were 1.04 (95% CI: 0.60, 1.81) for total 25(OH)D and 0.70 (95% CI: 0.41, 1.20) for free 25(OH)D. 25(OH)D was unrelated to AMH concentrations. VDBP was positively associated with early menopause; the OR comparing the highest with the lowest quartile of VDBP was 1.80 (95% CI: 1.09, 2.98).ConclusionsOur findings suggest that total and free 25(OH)D are not importantly related to the risk of early menopause. VDBP may be associated with increased risk, but replication is warranted.

Dataset Information

Menstrual Cycle Characteristics in Adolescence and Early Adulthood Are Associated With Risk of Early Natural Menopause.

Context

Objective

Design

Setting and participants

Main outcome measure(s)

Results

Conclusion

Publications

Menstrual Cycle Characteristics in Adolescence and Early Adulthood Are Associated With Risk of Early Natural Menopause.

Similar Datasets

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