Endometriosis tied to early natural menopause

Women with laparoscopically confirmed endometriosis appear to have an elevated risk of early natural menopause (ENM), a recent prospective study has shown.

Using the 1989–2015 questionnaires from the US Nurses’ Health Study II cohort, the researchers identified 106,633 premenopausal women aged 25–42 years at baseline (mean age 34.8 years) with no history of cancer, hysterectomy, or oophorectomy. Of these, 3,921 women had laparoscopically diagnosed endometriosis. The women were followed up until the first of ENM*, age 45 years, hysterectomy, oophorectomy, cancer diagnosis, death, loss to follow-up, or end of follow-up (May 2017). Menopausal status was assessed biennially.

A total of 6,640 women were diagnosed with endometriosis over 1,508,462 person-years of follow-up, while 2,542 women reported ENM only.

Compared with women without endometriosis, those with endometriosis had a higher likelihood of current use of acetaminophen (26.4 percent vs 21.3 percent) or non-steroidal anti-inflammatory drugs (25.2 percent vs 18.6 percent). Women with endometriosis were less likely to report never-use of oral contraceptives (11.3 percent vs 17.3 percent) and had a higher rate of prior infertility (58.6 percent vs 16.1 percent), infertility due to ovulatory disorder (15.4 percent vs 4.3 percent), and nulliparity (43.6 percent vs 30.4 percent). Women with endometriosis were also less likely to be overweight or obese at baseline and in late adolescence.

After adjusting for age and calendar time, the risk of developing ENM was increased among women with laparoscopically confirmed endometriosis compared with those without physician-diagnosed endometriosis (hazard ratio [HR], 1.51, 95 percent confidence interval [CI], 1.30–1.74). [JAMA Network Open 2022;5:e2144391]

The risk remained elevated after further adjustment for race and ethnicity and time-varying anthropometric and behavioural factors (HR, 1.46, 95 percent CI, 1.26–1.69), and was attenuated but remained significant after further adjustment for reproductive factors (HR, 1.28, 95 percent CI, 1.10–1.48).

When examining the ENM–endometriosis association, the risk was higher among women who were nulliparous vs parous (HRs, 1.46 and 1.14, respectively; p_{heterogeneity}=0.05) and those with no exposure to oral contraceptives vs ever-use (HRs, 2.03 and 1.20, respectively; p_{heterogeneity}=0.02).

“[It] is likely that oral contraceptive use masks menopause which is important to consider in this analysis particularly because women may use oral contraceptives to control endometriosis-associated symptoms,” the researchers commented on the latter finding.

The association between endometriosis and ENM did not differ according to body mass index (BMI; HRs 1.20 and 1.43 for BMI <25 and ≥25 kg/m², respectively; p_{heterogeneity}=0.34), never vs ever smoking (HRs, 1.36 and 1.11, respectively; p_{heterogeneity}=0.57), or presence or absence of prior infertility due to ovulatory disorder (HR, 1.28 for both; p_{heterogeneity}=0.86).

“This prospective cohort study found a statistically significant association between laparoscopically confirmed endometriosis and risk for ENM,” said the researchers.

“Endometriosis may be an important risk factor for ENM, and women with endometriosis, particularly those who are nulliparous and never-users of oral contraceptives, may be at a higher risk for a shortened reproductive duration,” they pointed out.