Clinicians have long observed that women with endometriosis tend to sleep poorly, but the relationship has been dismissed as secondary to chronic pain. A new study published in Functional & Integrative Genomics turns that assumption on its head, marshaling evidence from epidemiology, genetics, and molecular biology to argue that sleep disorders and endometriosis share biological machinery, and that sleep disruption may actually precede the disease.
The study, led by Licong Shen, Jun Chen, and Yongwen Yang at Central South University in Changsha, China, is the first to apply a multi-layered framework, epidemiological survey data, bidirectional Mendelian randomization, and multi-omics integration, to the endometriosis-sleep question.
What the numbers show
The researchers analyzed 1,460 women aged 20 to 54 from the 2005–2006 cycle of the National Health and Nutrition Examination Survey (NHANES). Among women who reported a clinician diagnosis of endometriosis, 13.4% also reported a clinician-diagnosed sleep disorder, compared with 5.1% of women without endometriosis. After adjusting for age, race, education, body mass index, smoking, and alcohol use, endometriosis was associated with 2.64 times higher odds of having a diagnosed sleep disorder (95% CI 1.03 – 6.76, p = 0.044).
Sensitivity analyses strengthened the finding. The association held when the researchers excluded pregnant women (OR 2.67) and women with cancer (OR 3.15), and when they substituted a broader outcome, “trouble sleeping,” for the clinician-diagnosed sleep disorder variable (OR 2.24). Only when the model was extended to include 13 additional covariates, marital status, income, physical activity, depression, asthma, arthritis, and thyroid disease, did the estimate attenuate and lose statistical precision (OR 2.19, p = 0.108), suggesting that some of the link runs through these correlated factors.
Which comes first: The genetics point toward sleep disruption driving endometriosis
To test directionality, the team performed two-sample Mendelian randomization, leveraging genetic variants as instruments. The forward analysis, testing whether genetic predisposition to sleep disorders increases endometriosis risk, returned a modest but nominally significant odds ratio of 1.11 (95% CI 1.00 – 1.22, p = 0.040) using 145 SNPs. The reverse analysis, whether genetic liability to endometriosis increases sleep disorder risk, found no evidence of an effect (OR 0.997, p = 0.939), though only two genetic instruments were available, limiting statistical power.
The authors interpret the forward MR result as “suggestive rather than definitive,” noting that the confidence interval barely excludes the null. But the asymmetry, a signal in one direction and not the other, hints that sleep disruption may be a causal contributor to endometriosis risk rather than merely a consequence of the disease.
Thirty-seven shared molecular candidates
The study’s most technically ambitious component was a disease-specific xQTL integration, which overlapped endometriosis-related expression quantitative trait locus (eQTL) genes with sleep disorder-related protein QTL (pQTL) genes. The intersection yielded 37 shared gene and protein candidates.
Pathway enrichment pointed to glucose metabolism, MAPK signaling, and thyroid hormone signaling, pathways that are plausible bridges between sleep regulation and endometrial biology. Transcriptomic validation across eight independent Gene Expression Omnibus datasets confirmed differential expression of several candidates in endometriosis versus control tissue. Machine-learning models, generalized linear models, extreme gradient boosting, support vector machines, and random forests, ranked the candidates by predictive importance. Single-cell RNA sequencing localized expression of the top candidates, SPARC and YEATS4, to stromal cells within endometrial tissue.
Exploratory molecular docking simulations suggested that SPARC, the strongest convergent candidate, has binding affinity for compounds including 11-cis-retinal, 4-aminobutyric acid, and beta-glycerophosphoric acid. The authors emphasize that these docking results are hypothesis-generating, not evidence of therapeutic efficacy.
What the study cannot say
Several limitations temper the findings. The NHANES data rely on participant-reported clinician diagnoses, not independently verified medical records, and the 2005–2006 cycle is now two decades old. The sleep disorder variable is a single binary item that collapses insomnia, sleep apnea, and other conditions into one category, precluding condition-specific analysis. The core adjusted model’s odds ratio, although statistically significant, has a wide confidence interval that reflects a modest effective sample size after survey-weighting. The forward MR result is borderline, and the reverse MR is underpowered. The molecular findings, while internally consistent, require prospective and experimental validation in disease-relevant tissues and animal models.
Bottom line
Endometriosis and sleep disorders appear to share convergent epidemiological, genetic, and molecular signals. The direction of the genetic evidence, sleep disruption preceding endometriosis risk rather than the reverse, challenges the clinical habit of treating poor sleep in endometriosis patients as merely symptomatic. If replicated, these findings suggest that screening for and treating sleep disorders could be a modifiable risk factor in the management of endometriosis, not just a consequence to be palliated.
Source: Shen L, Chen J, Yang Y. Systems-level genomic analyses reveal shared mechanisms underlying endometriosis and sleep disorders. Funct Integr Genomics. 2026 Jul 25;26(1):203. doi: 10.1007/s10142-026-01979-w. PMID: 42498900.