Context
Lower testosterone (T) levels have been associated with poorer health outcomes in older men, however, the relationship between T, dihydrotestosterone (DHT) and estradiol (E2) with cardiovascular disease (CVD) in younger men remains unclear.
Objectives
We assessed associations between endogenous sex hormones with mortality (all-cause and CVD) and CVD events, in community-dwelling men aged 17-97 years.
Participants and methods
T, DHT and E2 were assayed using liquid chromatography-mass spectrometry, and SHBG and LH using immunoassay, in 2,143 men from the 1994/5 Busselton Health Survey. Outcomes of death from any cause, CVD mortality and CVD events were recorded to December 2010 by data linkage. Cox proportional hazards regression was performed, adjusting systematically for age and other cardiovascular risk factors.
Results
Of the 1,804 men included in the analysis, there were 319 deaths, 141 CVD deaths, and 399 CVD events. Compared to the full cohort, men who died were older (70.4±11.0 vs 50.3±16.8 years), and had lower baseline T (12.0±4.4 vs 13.6±4.9 nmol/L) and DHT (1.65±0.64 vs 1.70±0.72 nmol/L), but higher E2 (64.0±32 vs 60.1±30.2 pmol/L). After adjustment for risk factors, T was not associated with mortality (adjusted HR=0.90, 95% CI 0.79-1.04; p=0.164 for every increase in 1 SD of T), CVD deaths (adjusted HR=1.04, 95% CI 0.84-1.29; p=0.708) or CVD events (adjusted HR=1.03, 95% CI 0.92-1.15, p=0.661). No associations were found for DHT, E2, SHBG or LH in the fully-adjusted analyses. Results were similar when the analysis was restricted to men free of CVD at baseline.
Conclusions
In men aged 17-97 years, T, DHT and E2 were not associated with mortality or CVD outcomes. This neutral association of hormones with CVD contrasts with prior studies in older men. Future interventional studies are warranted to assess the effects of T supplementation on risk of CVD events in men across ages.