SAT-156 Associations of Testosterone, Dihydrotestosterone and Sex Hormone-binding Globulin with Risks of Cancer Death, Incident Cancer, and Incident Prostate Cancer in Men. Individual Participant Data Meta-analyses

Abstract Disclosure: R.J. Marriott: None. K. Murray: None. L. Antonio: None. S. Bhasin: None. A.S. Dobs: None. L. Flicker: None. D.J. Handelsman: None. G.J. Hankey: None. R. Wilkening: None. A.M. Matsumoto: None. C. Ohlsson: None. E.S. Orwoll: None. D.M. Vanderschueren: None. H.W. Vesper: None. G.A. Wittert: None. F.C. Wu: None. B.B. Yeap: None. Aims: Whether differences in sex hormones relate to cancer, particularly prostate cancer, risk in men remains uncertain. We sought to clarify associations of testosterone, dihydrotestosterone and sex hormone-binding globulin (SHBG) with cancer risk via individual participant data (IPD) meta-analyses of major prospective cohort studies of community-dwelling men with testosterone measured using mass spectrometry. Methods: Eligible studies were identified via systematic literature review to July 2019, with bridge searches to March 2024. Ten studies provided IPD (24,510 men; 276,931 participant-years; 2847 cancer deaths), one provided aggregate data (1535 men; 184 cancer deaths). Five studies provided IPD for incident prostate cancer (12,280 men; 151,373 participant-years; 918 events). Two-stage random effects meta-analyses controlled for age, prior cancer, BMI, marital status, alcohol, smoking, physical activity, hypertension and diabetes. Results: Men with baseline testosterone at or below the lowest quintile median (Q1; 8.2 nmol/L), had higher risk of cancer death relative to Q5 (Q1:Q5 hazard ratio [HR]=1.15, 95% confidence interval [CI]=1.01-1.31). Baseline testosterone was not associated with risk of incident non-fatal and fatal cancer, nor incident prostate cancer. Men with lower baseline dihydrotestosterone had a higher risk of cancer death (Q1:Q5 HR=1.21, 95%CI=1.04-1.41), but not incident fatal and non-fatal cancer. SHBG was non-linearly associated with risk of cancer death (Q3:Q5 HR=0.79, 95%CI=0.66-0.95; Q4:Q5 HR=0.85, 95%CI=0.76-0.96). SHBG was not associated with incident non-fatal and fatal cancer. Men with lower baseline SHBG had higher risk of incident prostate cancer (Q1:Q5, HR=1.31, 95%CI=1.08-1.60; Q2:Q5 HR=1.26, 95%CI=1.04-1.52). Relative heterogeneity was negligible to moderate (estimates of I2 had 95%CI from 0.0-65.4%). Summary estimates from IPD were robust to the inclusion of aggregate data. Conclusions: Men with lower testosterone or dihydrotestosterone concentrations had higher risk, and men with mid-range SHBG lower risk, of cancer death. Testosterone was not associated with prostate cancer risk, while men with lower SHBG had a higher risk of incident prostate cancer. Testosterone, dihydrotestosterone and SHBG are biomarkers for cancer risk. The association between SHBG and prostate cancer risk merits further evaluation. Presentation: Saturday, July 12, 2025