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TOPLINE:

Women with primary infertility undergo natural menopause approximately 1 year earlier than women without infertility and face an increased risk for early menopause (age, 40-45 years). Those with endometriosis-related infertility experience menopause nearly 3 years earlier, while women with unexplained infertility undergo menopause about 1.5 years earlier than referent individuals.

METHODOLOGY:

• Researchers conducted a retrospective cohort study using data from the Mayo Primary Infertility Cohort (MPIC), which included 1001 women diagnosed with primary infertility between January 1, 1980, and December 31, 1999, and 1001 age-matched referent women from Olmsted County, Minnesota.
• A total of 461 women with primary infertility and 530 referent individuals expected to have natural menopause were included in the analysis, with 340 women with infertility and 346 referent women having documented natural menopause during the study period.
• Primary infertility was defined as inability to conceive for 12 months in individuals younger than 35 years and for 6 months in individuals 35 years or older, with infertility types including ovulatory dysfunction, male factor, tubal factor, uterine factor, endometriosis, and unexplained infertility.
• Researchers used Cox proportional hazard models to compare the risk for natural menopause and linear regression models to evaluate the association between age at natural menopause and infertility status, adjusting for BMI, tobacco use, race, menstrual cycle regularity, and previous contraception use.
• Natural menopause was defined as 12 months after the last reported menstrual period, and age at menopause was classified as premature (< 40 years), early (40-44 years), normal (45-54 years), or late (≥ 55 years).

TAKEAWAY:

• Women with primary infertility had an increased risk for natural menopause during the study period compared with referent women (hazard ratio [HR], 1.25; 95% CI, 1.06-1.46; P = .006) after adjustment for BMI, tobacco use, race, menstrual cycle regularity, and previous contraception use.
• Among women who underwent natural menopause, those with primary infertility experienced menopause 1.17 years earlier than referent individuals (95% CI, -0.82 to -0.52; P = .0005) after adjustment for confounding factors.
• Women with endometriosis underwent menopause 2.75 years earlier than referent women (95% CI, -4.38 to -1.13; P = .0009), and women with unexplained infertility underwent menopause 1.45 years earlier (95% CI, -2.26 to -0.64; P = .0005).
• Women with primary infertility were more likely to undergo early menopause (age, 40-45 years) than referent women (7.6% vs 3.0%, P = .01), while referent women were more likely to undergo late menopause (≥ 55 years) than women with primary infertility (17.3% vs 11.8%).

IN PRACTICE:

“Women with primary infertility may benefit from additional counseling and should be encouraged to pursue evaluation and treatment with new-onset secondary amenorrhea,” wrote the authors of the study.

SOURCE:

The study was led by Lillian J. Dyre, MD, Department of Obstetrics and Gynecology, Mayo Clinic College of Medicine and Science, and Alessandra J. Ainsworth, MD, Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Mayo Clinic, Rochester, Minnesota. It was published online in Menopause.

LIMITATIONS:

According to the authors, the age of menopause is subject to recall bias because it reflects a past event, and many women from the original cohort were excluded due to unknown menopausal status or unknown age at menopause. The results could be biased by different follow-up periods for women with infertility compared with control individuals, and parity information past the index date was not available, so full reproductive outcomes remain unknown. The geographic location of the cohort limits ethnic and racial diversity, with a higher proportion of White, highly educated women with normal BMI than the general population, which limits generalizability. While the analysis adjusted for known confounders including BMI, tobacco use, race, menstrual cycle regularity, and previous contraception use, other confounders may further influence the results.

DISCLOSURES:

The MPIC utilized resources from the Rochester Epidemiology Project medical records-linkage system, which receives support from the National Institute on Aging (grant AG058738), the Mayo Clinic Research Committee, and annual fees paid by users. Elizabeth A. Stewart, MD, disclosed receiving grants for her institution from the Patient-Centered Outcomes Research Institute and the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Office of Research on Women’s Health of the National Institutes of Health; holding a patent for Methods and Compounds for Treatment of Abnormal Uterine Bleeding; receiving royalties from UpToDate; receiving fees for developing educational content from the Physicians’ Education Resource, Omnia Education, Omnicuris, and WebMD; and having past financial relationships with AbbVie, Alnylam Pharmaceuticals, and Aska Pharmaceuticals. The remaining authors reported having no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.