Association of Sleep Traits, Physical Activity, and Sedentary Leisure Behavior With Female Reproductive Health: A Two-Sample Mendelian Randomization Analysis

Purpose: Living habits affect female endocrine function and fertility, along with aging and other life factors. Because of this, female reproductive health can be promoted through living habit adjustment. Methods: We used two-sample Mendelian randomization analysis with summary datasets from a genome-wide association study to investigate the causal relationships between sleep traits, sedentary leisure behavior, physical activity, and reproductive health traits in women, calculating odds ratios (ORs) and 95% confidence intervals (CIs). Exposure genetic instruments were used for variants that were significantly related to traits. The inverse-variance weighted (IVW) method was used for the main analysis, and we also performed MR-Egger and weighted median analyses to supplement the sensitivity test. Horizontal pleiotropy was detected using the MRE intercept and MR-PRESSO methods, and heterogeneity was assessed using Cochran's Q statistics, IVW, and MR-Egger. Results: Insomnia showed a significant inverse causal association with endometriosis [OR (95% CI) IVW = 1.80 (1.16, 2.80), P = 0.009] and abnormal menstruation [OR (95% CI) IVW = 2.37 (1.34, 4.20), P = 0.003]. Sleep duration was negatively related to menopause age (beta IVW = -0.034, P = 0.001), and long sleep duration could be a protective factor of endometriosis [OR (95% CI) IVW = 0.07 (0.01, 0.72), P = 0.024]. Strenuous sports were also negatively correlated with female infertility [OR (95% CI) IVW = 0.10 (0.02, 0.68), P = 0.019]. Sensitivity analysis revealed no signs of horizontal pleiotropy or heterogeneity. Conclusion: Our findings suggest that insomnia is an adverse factor correlated with endometriosis and abnormal menstruation and that longer sleep duration protects against endometriosis. Adequate sleep and regular schedules may decrease the risk of endometriosis and abnormal menstruation, helping improve the reproductive health of women.