Urinary melatonin levels, sleep disruption, and risk of prostate cancer in elderly men.

Case-cohort study nested in the Age, Gene/Environment Susceptibility-Reykjavík (AGES-Reykjavík) cohort; 928 elderly Icelandic men without prostate cancer at baseline; first-morning urine collected; 6-STM measured by ELISA; prostate cancer outcomes included total PCa, advanced PCa, and lethal PCa; analysis used weighted Cox proportional hazards models (Prentice method) with adjustments for age, creatinine, family history of PCa, depression, sleep problems, diabetes; cortisol adjustment in sensitivity analyses.

Lower morning 6-sulfatoxymelatonin (6-STM) levels below the median were linked to higher risk of advanced PCa (HR 4.04; 95% CI 1.26–12.98) and lethal PCa (HR 4.83; 95% CI 1.26–18.45); overall PCa risk was not statistically significant (HR 1.47; 95% CI 0.94–2.30). Concludes that lower morning urinary melatonin metabolite is associated with increased risk of advanced or lethal PCa in older men; replication in larger prospective studies is needed; findings suggest melatonin disruption may be avoidable and merit further study on melatonin and PCa risk.

Single morning-void 6-STM measurement may not reflect long-term melatonin; small number of advanced/lethal events; follow-up short (median ~2.3 years); potential reverse causation; lack of data on vitamin D, Gleason grade, PSA history; missing stage for 35% of cases; restricted to elderly Icelandic men, limiting generalizability.