Background: Symptomatic hypogonadism is frequent and associated with increased risk of cardiovascular events. Hypogonadism is often treated with testosterone replacement. In a recent meta-analysis on adverse events in randomised placebo controlled testosterone replacement trials (RPCT), no differences between testosterone or placebo/non-intervention groups with regards to cardiovascular events or risk factors was observed. Conversely, a contemporary RPCT in elderly immobile patients was prematurely stopped due to increased rate of cardiovascular events in the actively treated patients. The cardiovascular risk in men on long-term testosterone treatment is largely unsettled.
Aim and method: We aimed at assessing the association between the exposure variable testosterone treatment and development of cardiovascular events in a cohort of all men in Denmark filing prescriptions for testosterone in the period 19972008. Three age and sex-matched controls per patient were randomly selected from the background population. Information on mortality, disease, drug use and social variables was acquired using four Danish nationwide registries.
Results: Seven thousand three hundred and thirty-three testosterone users were identified. Women and prior (before 1997) testosterone users were excluded, generating a study cohort of 4792 cases (aged 46.3±0.3; years±S.E.M.) and 14 376 controls (46.7±0.2 years), which was followed until December 2011. In the mean observation period (13.2±0.03 years) 858/1963 deaths were observed in cases/controls yielding an unadjusted total mortality odds-ratio of 1.38 (1.261.51, 95% CI, P<0.01) in cases vs controls and correspondingly a Cox proportional hazard-ratio of 1.36 (1.251.47, 95% CI). Unadjusted odds-ratio for cardiovascular death was 1.22 (1.041.43, 95% CI) in cases vs controls.
Conclusion: We found a significant 36% increased mortality in men treated with testosterone compared to age- and sex-matched controls. We also found an increased risk of cardiovascular death in the cases. However, in this on-going study additional analyses are needed to further clarify whether the observed increased mortality is connected with co-morbidity, concomitant drug.
27 Apr - 01 May 2013
European Society of Endocrinology