Risk of early natural menopause from oral contraceptives or tubal ligation

However, tubal ligation was associated with a modestly higher risk of early menopause.

“Early menopause puts women at risk for several adverse health outcomes later in life,” said senior author Christine Langton, PhD, a postdoctoral fellow in the Women's Health Group, Epidemiology Branch, at the National Institute of Environmental Health Sciences in Durham, North Carolina. “I was interested in examining potentially modifiable reproductive risk factors and their association with early menopause.”

Because oral contraceptives and tubal ligation are two commonly used methods of contraception, “it is important to have a clear understanding if and how they may be connected to menopause timing,” Langton told Contemporary OB/GYN®.

The research was conducted while Langton was a doctoral candidate in epidemiology at the School of Public Health & Health Sciences at the University of Massachusetts in Amherst.

The study authors hypothesized that the use of oral contraceptives might lower the risk of menopause before the age of 45 because they prevent pregnancy by manipulating hormone levels and preventing ovulation.

The study comprised 106,633 women within the prospective Nurses’ Health Study II cohort. Participants were premenopausal and aged 25 to 42 at baseline. The women were followed from 1989 to 2017, with response rates from 85% to 90% for each 2-year follow-up period.

By tracking over 1.6 million person-years, over 2,500 members of the analytic cohort experienced early natural menopause.

Multivariable models concluded that the duration, timing, and type of oral contraceptive were not associated with risk of early menopause.

Compared to women who never used oral contraceptives, those reporting more than 120 months of oral contraceptive use had a hazard ratio (HR) for early menopause of only 1.01; 95% confidence interval (CI): 0.87 to 1.17 (P for trend = 0.71).

Tubal ligation was connected to an increased risk of early menopause versus those women who did not have the procedure: HR = 1.17; 95% CI: 1.06 to 1.28.

“Although our oral contraceptive findings did not align with our hypothesis, we believe our study has many strengths, including the use of prospective data among premenopausal women; accounting for time-varying lifestyle factors in our statistical models; and our in-depth examination, according to various oral contraceptive characteristics,” Langton said.

Langton noted that, because the study was an epidemiologic study, it only examined associations between oral contraceptives, tubal ligation, and early menopause. “We are not suggesting that these contraceptive methods cause menopause timing,” she said. “There are many variables that determine menopause timing, including both genetic and lifestyle factors.”

The mechanism by which tubal ligation may impact menopause timing is unclear and warrants further research, according to Langton.

“Factors such as smoking, parity, and menstrual cycle pattern may also influence a woman’s menopause timing; hence, we feel it is important for women to discuss ways to prevent early menopause with their healthcare provider by taking into consideration all their individual risk factors,” Langton said.

Moreover, because anti-Müllerian hormone (AMH) is a well-established marker for timing of menopause and is often relied upon in a clinical setting, “understanding the association of oral contraceptives and tubal ligation to AMH is an important direction for future research,” Langton said.

Reference

1. Langton CR, Whitcomb BW, Purdue-Smithe AC, et al. Association of oral contraceptives and tubal ligation with risk of early natural menopause. Hum Reprod. 2021 Jul; 36(7): 1989–1998. doi:10.1093/humrep/deab054