Real-world evidence of the association between primary insomnia and early-onset hormone-related cancers.

11014 Background: Although progress has been made in reducing overall cancer incidence, early-onset cancers have continued their troublesome rise. Similarly, primary insomnia increases in incidence and prevalence each year, and with it come likelihoods of circadian disruption, immune dysregulation, and altered hormone signaling. However, real-world data characterizing the association between insomnia and early-onset hormone-associated malignancies remains limited. Methods: We sought to conduct a real-world, retrospective cohort study using the TriNetX United States Research Database, a federated network of de-identified electronic health records (EHRs) from over 70 healthcare organizations, to examine this association. Adults aged 18–50 years with primary insomnia (ICD-10: F51.01) were compared with same-aged individuals without primary insomnia using a five-year lookback period from January 25th, 2021 to January 25th 2026. Propensity score matching adjusted for demographic and clinical confounders. Incidence of early-onset cancers diagnosed within five years of the index event was assessed during follow-up. Sensitivity analyses required a ≥ 1-year lag between insomnia diagnosis and cancer onset. Results: 413,116 patients ages 18-50 were identified as having primary insomnia, whereas 18,437,709 patients ages 18-50 were identified as not having primary insomnia. Within 1-5 years of primary insomnia diagnosis, patients were more likely to develop early-onset breast cancer (RR 3.155, CI 2.863-3.477, p < 0.0001), uterine cancer (RR 1.988, CI 1.532-2.580, p < 0.0001), and ovarian cancer (RR 1.573, CI 1.276-1.940, p < 0.0001). Associations with early-onset prostate cancer (RR 1.676, CI 1.096-2.564) and testicular cancer (RR 1.243, CI 1.015-1.522) did not meet thresholds for significance. Conclusions: In this large, real-world cohort study, insomnia was associated with an increased risk of early-onset hormonal cancers more commonly affecting female patients. These findings suggest that sleep disruption may represent a clinically relevant, potentially modifiable risk factor in early-onset cancer risk stratification and warrants further investigation.