Causal Association Between Sleep Traits and Endometriosis: A Mendelian Randomization Study

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.

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.

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.

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.