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

Zhang J, Wang T, Yang P, Miao Y, Ge B, Sun J
2025 · W7054923315
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A two-sample Mendelian randomization analysis identified insomnia as a risk factor for endometriosis and abnormal menstruation, while longer sleep duration protected against endometriosis in women.

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This study employed a two-sample Mendelian randomization analysis to investigate the causal relationships between sleep traits, physical activity, and sedentary behavior with female reproductive health outcomes. The researchers analyzed summary datasets from genome-wide association studies using inverse-variance weighted methods and sensitivity tests to assess odds ratios and confidence intervals for various conditions. Key findings indicated that insomnia significantly increases the risk of endometriosis and abnormal menstruation, whereas longer sleep duration appears protective against endometriosis, and strenuous sports are negatively correlated with female infertility. This paper is centrally about endometriosis — specifically examining how genetic predispositions to sleep traits like insomnia and long sleep duration causally influence the development of endometriosis.

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Abstract

Jiaxin Zhang, Tao Wang, Pusheng Yang, Yaxin Miao, Beilei Ge, Jing Sun Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, 200092, People’s Republic of ChinaCorrespondence: Jing Sun, Email [email protected]; Beilei Ge, Email [email protected]: 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.Keywords: Mendelian randomization, reproductive health, lifestyle factors
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International Journal of Women's Health (Feb 2025) Association of Sleep Traits, Physical Activity, and Sedentary Leisure Behavior With Female Reproductive Health: A Two-Sample Mendelian Randomization Analysis Abstract Jiaxin Zhang, Tao Wang, Pusheng Yang, Yaxin Miao, Beilei Ge, Jing Sun Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, 200092, People’s Republic of ChinaCorrespondence: Jing Sun, Email [email protected]; Beilei Ge, Email [email protected]: 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.Keywords: Mendelian randomization, reproductive health, lifestyle factors

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