Dataset Information

Association of oral contraceptives and tubal ligation with risk of early natural menopause.

ABSTRACT:

Study question

What is the association of oral contraceptives (OCs) and tubal ligation (TL) with early natural menopause?

Summary answer

We 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 already

OCs 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, duration

We 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, methods

Participants 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 chance

Over 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 caution

Our 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 findings

To 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 number

N/A.

SUBMITTER: Langton CR

PROVIDER: S-EPMC8487650 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:Studies on relationship between tubal ligation and endometrial cancer have led to contradictory findings. In several studies, however, a reduced endometrial cancer risk was suggested following tubal ligation. Therefore, a systematic review and meta-analysis was conducted to examine the relationship between tubal ligation and endometrial cancer risk. METHODS:In this systematic review and meta-analysis, PubMed/Medline, Web of Science, Scopus, Embase, and Google Scholar were searched for relevant studies published up to May 30th, 2018. We compared endometrial cancer risk in women with and without tubal ligation in retrieved studies. RESULTS:Two hundred nine studies were initially retrieved from the data bases. After exclusion of duplicates and studies which did not meet inclusion criteria, ten cohort and case-control studies, including 6,773,066 cases, were entered into the quantitative meta-analysis. There was 0.90% agreement between two researchers who searched and retrieved the studies. The summary OR (SOR) was reported using a random effect model. Begg's test suggested that there was no publication bias, but a considerable heterogeneity was observed (I2 =?95.4%, P?=?0.001). We pooled the raw number of tables cells (i.e. a, b, c, and d) of eight studies. The SOR suggested that tubal ligation was significantly associated with a lower risk of endometrial cancer (SOR?=?0.577, 95% CI?=?0.420-0.792). Also, given the rare nature of endometrial cancer (<?5%), different effect sizes were considered as comparable measures of risk. Therefore we pooled ten studies and SOR of these studies revealed that tubal ligation was significantly associated with a lower risk of endometrial cancer (SOR?=?0.696, 95% CI?=?0.425-0.966). Besides that, we pooled eight studies in which adjusted effect sizes were reported and a subsequent analysis revealed that the summary estimate of adjusted odds ratio (SAOR) was significant (SAOR?=?0.862, 95% CI?=?0.698-1.026). CONCLUSIONS:This study revealed a protective effect of tubal ligation on endometrial cancer risk (approximately 42% lower risk of cancer). It is recommended that studies should be designed to reveal mechanisms of this relationship.