Objective: Although physical activity modulates the hypothalamic-pituitary-ovarian axis, the few studies that have investigated whether physical activity is associated with age at natural menopause have yielded mixed results. We set out to determine whether physical activity is associated with the timing of natural menopause in a large cohort of California women overall and by smoking history.
Methods: We investigated the association between long-term physical activity (h/wk/y) and age at natural menopause among 97,945 women in the California Teachers Study. Multivariable Cox proportional hazards regression methods were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). The impact of cigarette smoking (never smoker, former light smoker, former heavy smoker, current light smoker, and current heavy smoker) as an effect modifier was evaluated.
Results: In a multivariable model adjusted for body mass index at age 18 years, age at menarche, race/ethnicity, and age at first full-term pregnancy, increased physical activity was statistically significantly associated with older age at natural menopause (P(trend) = 0.005). Higher body mass index at age 18 years (P(trend) = 0.0003) and older age at menarche (P(trend) = 0.0003) were also associated with older age at natural menopause. Hispanic ethnicity (vs non-Hispanic whites; HR, 1.17; 95% CI, 1.09-1.26), current smokers (vs never smokers; HR, 1.68; 95% CI, 1.60-1.75 for current light smokers; HR, 1.38; 95% CI, 1.33-1.44 for current heavy smokers), and older age at first full-term pregnancy (HR(≥29, 2+ full-term pregnancies) vs HR(<29, 2+ full-term pregnancies), 1.10; 95% CI, 1.06-1.14) were associated with earlier age at natural menopause. Upon stratification by smoking history, increased physical activity was statistically significantly associated with older age at natural menopause among heavy smokers only (HR(highest quartile) vs HR(lowest quartile), 0.88; 95% CI, 0.81-0.97; P(trend) = 0.02 for former heavy smokers; HR(highest quartile) vs HR(lowest quartile), 0.89; 95% CI, 0.80-0.99; P(trend) = 0.04 for current heavy smokers).
Conclusions: Age at natural menopause is a complex trait; the determinants of age at natural menopause, including physical activity, may differ by smoking status.