Physical activity associated with age at menopause: A Mendelian randomization study

In previous observational studies, physical activity may have an impact on the age at menopause (ANM), potentially delaying or advancing the onset of menopause. However, the causal relationship between physical activity and age at menopause remains unclear. Therefore, we designed a 2-sample Mendelian randomization (MR) and mediation MR study to explore the causal relationship between physical activity and ANM and to identify potential mediating factors such as BMI, insomnia, hypertension and hyperglycemia. We investigated the causal link between physical activity and age at menopause using 2-sample Mendelian randomization (MR) and tested for potential mediators using 2-step MR. Our approach includes IVW and other MR methods and uses a variety of sensitivity tests to verify the robustness of the results. In 2-sample MR analysis, moderate physical activity was associated with delayed age at menopause (β = 0.64, 95% CI = [0.02-1.26], P = .04), but there was no evidence of a causal relationship between vigorous physical activity and age at menopause (P = .68).In contrast, a 2-step MR method showed that body mass index (BMI) mediated the effects of physical activity and delayed age at menopause (proportion mediated, 4.9%, 95% CI = 0.8 to 8%; P = .02), whereas the mediating effects of insomnia, hypertension and hyperglycemia were not significant. Our study shows that moderate physical activity can delay the age of menopause and is informative for the prevention of ovarian failure and the maintenance of women's reproductive health.