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已发表论文
睡眠特征与子宫内膜异位症之间的因果关联：一项孟德尔随机化研究
Authors Li J, Wan W, Hu L , Ren Y , Ge L, Liu Y, Liu P, Cui L
Received 17 September 2025
Accepted for publication 9 January 2026
Published 6 February 2026 Volume 2026:18 565217
DOI https://doi.org/10.2147/IJWH.S565217
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Vinay Kumar
Jincheng Li,1 Wenjing Wan,1– 8 Linlin Hu,2– 8 Yujia Ren,1– 8 Li Ge,1 Yue Liu,1 Peihao Liu,2– 8 Linlin Cui1
1Center for Reproductive Medicine, The Second Qilu Hospital of Shandong University, Jinan, Shandong, 250012, People’s Republic of China; 2State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Shandong University, Jinan, 250012, People’s Republic of China; 3National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, Shandong, 250012, People’s Republic of China; 4Key Laboratory of Reproductive Endocrinology (Shandong University), Ministry of Education, Jinan, Shandong, 250012, People’s Republic of China; 5Shandong Technology Innovation Center for Reproductive Health, Jinan, Shandong, 250012, People’s Republic of China; 6Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, Shandong, 250012, People’s Republic of China; 7Shandong Key Laboratory of Reproductive Research and Birth Defect Prevention (Under Construction), Jinan, Shandong, 250012, People’s Republic of China; 8Research Unit of Gametogenesis and Health of ART-Offspring, Chinese Academy of Medical Sciences (No.2021RU001), Jinan, Shandong, 250012, People’s Republic of China
Correspondence: Linlin Cui, Center for Reproductive Medicine, The Second Qilu Hospital of Shandong University, No. 247, Beiyuan Road, Tianqiao District, Jinan, Shandong, People’s Republic of China, Tel +86 531 85651188, Email fdclear3@126.com Peihao Liu, State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Shandong University, No. 157, Jingliu Road, Shizhong District, Jinan, Shandong, 250012, People’s Republic of China, Tel +86 531 87909000, Email liupeihao@sduivf.com
Purpose: Previous studies suggested that irregular sleep-wake rhythms increased the risk of endometriosis. Mechanistically, sleep pattern dysregulation may promote the pathogenesis of endometriosis via neuroendocrine disturbances. However, the causal relationship between sleep traits and endometriosis remains unclear. We aim to investigate the potential causal associations between sleep traits and endometriosis, including its specific anatomical subtypes.
Patients and Methods: Two-sample Mendelian Randomization (MR) analyses were conducted. The primary exposure was insomnia, and the secondary exposures were getting up in the morning, nap during day, sleep disorders, chronotype, snoring, short sleep duration, and long sleep duration. The outcomes were endometriosis along with its anatomical subtypes: uterine, ovarian, vaginal, intestinal, peritoneal, and unspecified endometriosis. We applied inverse variance weighted (IVW), weighted median, simple mode, weighted mode, and MR-Egger regression to estimate causal relationships between sleep traits and the risk of endometriosis. Additionally, a series of sensitivity and validation analyses were performed to ensure robustness.
Results: For the primary exposure, IVW results suggested that insomnia was significantly associated with elevated risks of endometriosis (OR=1.83, 95% CI: 1.34– 2.50), uterine endometriosis (OR=2.22, 95% CI: 1.30– 3.80), ovarian endometriosis (OR=1.61, 95% CI: 1.03– 2.54), vaginal endometriosis (OR > 1.00, 95% CI: 1.03– 3.79) and unspecified endometriosis (OR=2.70, 95% CI: 1.45– 5.02). For the secondary exposure, most sleep traits showed no significant associations with endometriosis risk.
Conclusion: Our study demonstrated a causal relationship between insomnia and elevated risks of endometriosis across multiple anatomical subtypes. While no significant associations were observed for other sleep traits, the robust link with insomnia highlights the potential clinical value of sleep-focused interventions in mitigating the risk of endometriosis.
Keywords: endometriosis, genetic association, Mendelian randomization, insomnia, sleep traits
1Center for Reproductive Medicine, The Second Qilu Hospital of Shandong University, Jinan, Shandong, 250012, People’s Republic of China; 2State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Shandong University, Jinan, 250012, People’s Republic of China; 3National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, Shandong, 250012, People’s Republic of China; 4Key Laboratory of Reproductive Endocrinology (Shandong University), Ministry of Education, Jinan, Shandong, 250012, People’s Republic of China; 5Shandong Technology Innovation Center for Reproductive Health, Jinan, Shandong, 250012, People’s Republic of China; 6Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, Shandong, 250012, People’s Republic of China; 7Shandong Key Laboratory of Reproductive Research and Birth Defect Prevention (Under Construction), Jinan, Shandong, 250012, People’s Republic of China; 8Research Unit of Gametogenesis and Health of ART-Offspring, Chinese Academy of Medical Sciences (No.2021RU001), Jinan, Shandong, 250012, People’s Republic of China
Correspondence: Linlin Cui, Center for Reproductive Medicine, The Second Qilu Hospital of Shandong University, No. 247, Beiyuan Road, Tianqiao District, Jinan, Shandong, People’s Republic of China, Tel +86 531 85651188, Email fdclear3@126.com Peihao Liu, State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Shandong University, No. 157, Jingliu Road, Shizhong District, Jinan, Shandong, 250012, People’s Republic of China, Tel +86 531 87909000, Email liupeihao@sduivf.com
Purpose: Previous studies suggested that irregular sleep-wake rhythms increased the risk of endometriosis. Mechanistically, sleep pattern dysregulation may promote the pathogenesis of endometriosis via neuroendocrine disturbances. However, the causal relationship between sleep traits and endometriosis remains unclear. We aim to investigate the potential causal associations between sleep traits and endometriosis, including its specific anatomical subtypes.
Patients and Methods: Two-sample Mendelian Randomization (MR) analyses were conducted. The primary exposure was insomnia, and the secondary exposures were getting up in the morning, nap during day, sleep disorders, chronotype, snoring, short sleep duration, and long sleep duration. The outcomes were endometriosis along with its anatomical subtypes: uterine, ovarian, vaginal, intestinal, peritoneal, and unspecified endometriosis. We applied inverse variance weighted (IVW), weighted median, simple mode, weighted mode, and MR-Egger regression to estimate causal relationships between sleep traits and the risk of endometriosis. Additionally, a series of sensitivity and validation analyses were performed to ensure robustness.
Results: For the primary exposure, IVW results suggested that insomnia was significantly associated with elevated risks of endometriosis (OR=1.83, 95% CI: 1.34– 2.50), uterine endometriosis (OR=2.22, 95% CI: 1.30– 3.80), ovarian endometriosis (OR=1.61, 95% CI: 1.03– 2.54), vaginal endometriosis (OR > 1.00, 95% CI: 1.03– 3.79) and unspecified endometriosis (OR=2.70, 95% CI: 1.45– 5.02). For the secondary exposure, most sleep traits showed no significant associations with endometriosis risk.
Conclusion: Our study demonstrated a causal relationship between insomnia and elevated risks of endometriosis across multiple anatomical subtypes. While no significant associations were observed for other sleep traits, the robust link with insomnia highlights the potential clinical value of sleep-focused interventions in mitigating the risk of endometriosis.
Keywords: endometriosis, genetic association, Mendelian randomization, insomnia, sleep traits