Background: Sex steroid hormones (estrogen, androgen) regulate reproduction but also mediate metabolic, cardiovascular, and skeletal homeostasis. Small-scale studies link aberrant male estrogen/female androgen levels to pathologies, yet population-level evidence for their associations with common chronic diseases remains fragmented.
Research questions: 1) Are male circulating estrogen levels independently associated with incidence of cardiovascular disease (CVD), type 2 diabetes (T2D), metabolic syndrome, and osteoporosis in the UK Biobank cohort? 2) Do female circulating androgen levels correlate with onset risk of these diseases and polycystic ovary syndrome (PCOS)-related comorbidities? 3) Do age, BMI, or lifestyle factors modify these hormone-disease associations?
Objectives: 1) Characterize male estrogen/female androgen distributions across UK Biobank demographic subgroups; 2) Quantify the strength/dose-response of hormone-disease links via multivariable Cox proportional hazards models; 3) Evaluate effect modification by age, BMI, and physical activity.
Scientific rationale: The UK Biobank’s large baseline hormone measurements, long-term chronic disease follow-up, and comprehensive covariates enable robust analysis of these understudied associations. Findings will refine chronic disease risk profiles, inform personalized prevention for hormone-related phenotypes, and address endocrine epidemiology gaps-ultimately supporting evidence-based public health risk stratification.
