Associations between lifetime tobacco exposure with infertility and age at natural menopause: The women’s health initiative observational study

Background: Several studies have investigated the association of tobacco use with infertility and age at natural menopause, yet few have explored secondhand smoke (SHS) exposure with these outcomes. This study offers a comprehensive, quantified secondary data analysis of these issues using the Women’s Health Initiative Observational Study (WHI OS). Purpose: This study examines associations between lifetime tobacco exposure-active smoking and SHS- and infertility and natural menopause (before age 50). Methods: Information on smoking, lifetime fertility status, and age at natural menopause was collected and available from 93 676 postmenopausal women aged 50-79 enrolled in the WHI OS from 1993 to 1998 at 40 centres in the USA. Multivariate-adjusted regression models were used to estimate ORs and 95% CI according to levels of active smoking and SHS exposure, and trends were tested across categories. Results: Overall, 15.4% of the 88 732 women included in the analysis on infertility met criteria for the condition. 45% of the 79 690 women included in the analysis on natural menopause (before age 50) met criteria for the condition. Active-ever smokers had overall OR’s of 1.14 (95% CI 1.03 to 1.26) for infertility, and 1.26 (95% CI 1.16 to 1.35) for earlier menopause than never-smoking women. Never-smoking women with the highest levels of lifetime SHS exposure had adjusted OR’s of 1.18 (95% CI 1.02 to 1.35) for infertility, and 1.18 (95% CI 1.06 to 1.31) for earlier menopause. Active-ever smokers reached menopause 21.7 months earlier than the mean of 49.4 years for never-smokers not exposed to SHS, and women exposed to the highest level of SHS reached menopause 13.0 months earlier. Conclusions: Active smoking and SHS exposure are associated with increased risk of infertility and natural menopause occurring before the age of 50 years.