Infertility and age of menopause in a longitudinal cohort of women with primary infertility

OBJECTIVES: To analyze the association between primary infertility and infertility type with the age of natural menopause. METHODS: This is a retrospective cohort study reviewing a subset of women from the Mayo Primary Infertility Cohort (MPIC). The MPIC is a cohort of 1,001 women diagnosed with primary infertility and 1,001 age-matched referent women. In this study, we included all women at risk for natural menopause and further evaluated those who had reported natural menopause in the medical record. We compared the risk of natural menopause using Cox proportional hazard models with infertility status and infertility type as covariates. In those with documented menopause during the study period, the association between primary infertility and early and premature menopause was analyzed with χ2 testing. We evaluated the association between age at natural menopause, primary infertility status, and infertility type in this group using linear regression. RESULTS: In all, 461 women with primary infertility, with 530 referent individuals, were at risk of natural menopause, and of these, 340 women with infertility and 346 referent women underwent documented natural menopause on review of medical records. Women with primary infertility had an increased risk of natural menopause (hazard ratio: 1.25, 95% CI: 1.06-1.46) and underwent menopause 1 year earlier than referent individuals (β=-1.17, 95% CI: -1.82 to -0.52) after adjustment for body mass index, tobacco use, race, menstrual cycle regularity, and previous contraception use. Women with primary infertility were more likely to undergo early menopause (age 40-45) than referent women (7.6% vs. 3.0%, P=0.01). Compared with referent women, women with endometriosis underwent menopause 2.75 years earlier (95% CI: -4.38 to -1.13, P=0.0009), and women with unexplained infertility underwent menopause 1.45 years earlier (95% CI: -2.26 to -0.64, P=0.0005). CONCLUSIONS: Women with primary infertility had an increased risk of early menopause and collectively underwent menopause 1 year earlier than women without a history of primary infertility.