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已发表论文
睡眠中断和轮班工作与生殖内分泌紊乱风险增加有关：来自英国生物银行和孟德尔随机化的证据
Authors Zhang H , Luo R, Fang Y, Wang H, Li Y
Received 30 September 2025
Accepted for publication 25 December 2025
Published 8 January 2026 Volume 2026:18 571454
DOI https://doi.org/10.2147/IJWH.S571454
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 3
Editor who approved publication: Dr Vinay Kumar
Hanke Zhang,* Ruyu Luo,* Yuqing Fang, Hongbo Wang, Yanhui Li*
Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Yanhui Li, Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Avenue, Wuhan, Hubei, 430022, People’s Republic of China, Tel +86 13407159190, Email liyanhui251@163.com
Background: Disrupted sleep and shift work are linked to multiple adverse health outcomes, but their association with reproductive endocrine disorders (REDs) and underlying mechanisms remain unclear. Understanding this relationship is crucial for public health, given the growing prevalence of sleep disturbances and shift work in modern societies.
Purpose: To investigate the impact of sleep traits and shift work on RED risk in women, explore inflammatory mediation, and assess potential causality using Mendelian randomisation (MR).
Methods: We analysed 244,561 women in the UK Biobank. Sleep duration, quality, and shift work were self-reported. Cox models estimated hazard ratios (HRs) adjusting for demographic, lifestyle, and comorbidities. Interaction models tested joint effects of sleep and shift work. Mediation analyses examined inflammatory biomarkers. Two-sample MR analyses were conducted using large-scale genome-wide association study (GWAS) summary statistics to evaluate causal effects of sleep length or sleep quality traits on REDs.
Results: A U-shaped association was observed between sleep duration and RED risk, lowest at 7 h/day. Short (≤ 5 h/day; HR = 1.15, 95% CI: 1.02– 1.31) and long (≥ 9 h/day; HR = 1.16, 95% CI: 1.04– 1.29) sleep duration, poor sleep quality, and night shift work (HR = 1.40, 95% CI: 1.11– 1.75) independently increased RED risk. The combination of night shift work and ≤ 5 h/day sleep duration showed the highest risk (HR = 1.72, p = 0.0219). Neutrophils, CRP, and leukocytes mediated 5– 13% of these associations. MR analyses supported significant causal effects of short sleep duration, insomnia, and daytime napping on REDs.
Conclusion: Abnormal sleep duration, insomnia, and night shift work are independent risk factors for REDs in women, with inflammation partially mediating these associations. The highest risk was observed in women with short sleep combined with night shift work. MR analyses provide genetic evidence for the causal role of short sleep, insomnia, and daytime napping in REDs. These findings highlight the importance of screening for sleep disturbances and shift work in RED risk assessment, suggesting that interventions targeting sleep duration and shift work schedules may help reduce RED incidence and improve reproductive health. This study is the first to integrate both prospective and genetic evidence to identify causal pathways.
Keywords: sleep duration, shift work, reproductive endocrine disorders, inflammation, Mendelian randomisation, UK Biobank
Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Yanhui Li, Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Avenue, Wuhan, Hubei, 430022, People’s Republic of China, Tel +86 13407159190, Email liyanhui251@163.com
Background: Disrupted sleep and shift work are linked to multiple adverse health outcomes, but their association with reproductive endocrine disorders (REDs) and underlying mechanisms remain unclear. Understanding this relationship is crucial for public health, given the growing prevalence of sleep disturbances and shift work in modern societies.
Purpose: To investigate the impact of sleep traits and shift work on RED risk in women, explore inflammatory mediation, and assess potential causality using Mendelian randomisation (MR).
Methods: We analysed 244,561 women in the UK Biobank. Sleep duration, quality, and shift work were self-reported. Cox models estimated hazard ratios (HRs) adjusting for demographic, lifestyle, and comorbidities. Interaction models tested joint effects of sleep and shift work. Mediation analyses examined inflammatory biomarkers. Two-sample MR analyses were conducted using large-scale genome-wide association study (GWAS) summary statistics to evaluate causal effects of sleep length or sleep quality traits on REDs.
Results: A U-shaped association was observed between sleep duration and RED risk, lowest at 7 h/day. Short (≤ 5 h/day; HR = 1.15, 95% CI: 1.02– 1.31) and long (≥ 9 h/day; HR = 1.16, 95% CI: 1.04– 1.29) sleep duration, poor sleep quality, and night shift work (HR = 1.40, 95% CI: 1.11– 1.75) independently increased RED risk. The combination of night shift work and ≤ 5 h/day sleep duration showed the highest risk (HR = 1.72, p = 0.0219). Neutrophils, CRP, and leukocytes mediated 5– 13% of these associations. MR analyses supported significant causal effects of short sleep duration, insomnia, and daytime napping on REDs.
Conclusion: Abnormal sleep duration, insomnia, and night shift work are independent risk factors for REDs in women, with inflammation partially mediating these associations. The highest risk was observed in women with short sleep combined with night shift work. MR analyses provide genetic evidence for the causal role of short sleep, insomnia, and daytime napping in REDs. These findings highlight the importance of screening for sleep disturbances and shift work in RED risk assessment, suggesting that interventions targeting sleep duration and shift work schedules may help reduce RED incidence and improve reproductive health. This study is the first to integrate both prospective and genetic evidence to identify causal pathways.
Keywords: sleep duration, shift work, reproductive endocrine disorders, inflammation, Mendelian randomisation, UK Biobank