Testosterone and cardiovascular risk: meta-analysis of observational and interventional studies
Corona, G1; Rastrelli, G2; Di Pasquale, G1; Sforza, A1; Mannucci, E2; Maggi, M2
1: Maggiore-Bellaria Hospital, Bologna; 2: University of Florence, Italy
Objective. The relationship between testosterone (T) and cardiovascular (CV) risk in men is conflicting. By using a meta-analytic approach, we aimed at evaluating i) the relationship between endogenous low T levels and incident CV events and ii) the risk of incident CV diseases and CV mortality associated with T therapy.
Material and Methods. We conducted a random effect meta-analysis considering all available data from prospective observational and pharmaco-epidemiological studies as well as randomized placebo-controlled trials (RCTs).
Results. After screening, 37 observational, 15 pharmaco-epidemiological and 93 RCT studies were considered. Low endogenous T at enrolment predicts overall and CV mortality, as well as CV morbidity when both unadjusted and fully adjusted models were considered. In addition, the analysis of pharmaco-epidemiological studies documented that T therapy (TTh) reduces overall mortality and CV morbidity. Conversely, in RCTs TTh had no clear effect, either beneficial or detrimental, on the incidence of CV events. However, a protective role of TTh on CV morbidity was observed when studies enrolling obese (BMI > 30 kg/m2) patients were scrutinized (MH-OR= 0.51[0.27;0.96]; p=0.04), although this association disappeared when only high quality RCTs were considered (MH-OR= 0.64[0.22;1.88]; p=0.42). Finally, an increased risk of CV diseases was observed in RCTs when T preparations were prescribed at dosages above those normally recommended, or when frail men were considered.
Conclusions. Low T is a biomarker of CV risk. Data from RCTs suggest that treatment with T is not effective in reducing this risk, however, when TTh is correctly applied, it is not associated with an increase in CV risk and it may have a beneficial effect in some sub-populations.
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