Individual participant data meta-analyses of associations of testosterone, SHBG, and related hormones with cancer death, incident cancer, and incident prostate cancer in men

Whether differences in sex hormones influence cancer risk in men is uncertain. Individual participant data (IPD) meta-analyses investigated the association of circulating testosterone, sex hormone-binding globulin (SHBG), and related hormones with risks of cancer death, incident cancer, an incident prostate cancer. Prospective cohort studies comprising 1000 or more community-dwelling men and follow-up of 5 years or more were included. Ten studies provided IPD (24 510 men; 276 931 participant years; 2847 cancer deaths) and one provided aggregate data (1535 men; 184 cancer deaths). Five studies provided IPD for incident prostate cancer. Lower total testosterone concentration were associated with higher risk of cancer deaths (median of first versus median of fifth quintile HR 1.18; 95% CI 1.04-1.34), as were lower dihydrotestosterone concentrations (1.21; 1.06-1.38), the risk increasing with testosterone concentration less than 8.6 nmol/L. SHBG and luteinising hormone concentrations were non-linearly associated with risk of cancer death. Men with very low baseline testosterone concentration had a higher risk of incident cancer, the risk increasing with concentrations less that 7.3 nmol/L. Lower SHBG or lower luteinising hormone concentrations were associated with higher risk of incident prostate cancer; testosterone was not associated with this outcome. Heterogeneity across most analyses was negligible to moderate. The authors conclude that sex hormones could serve as biomarkers for cancer risk.