CARDIOVASCULAR SAFETY OF TESTOSTERONE REPLACEMENT THERAPY IN MEN: AN UPDATED SYSTEMATIC REVIEW AND META- ANALYSIS

The cardiovascular (CV) safety of testosterone (T) replacement therapy (TRT) is still conflicting.

Recent data suggested a TRT-related increased risk of atrial fibrillation (AF). To systematic review and meta-analyze CV risk related to TRT as derived from placebo-controlled randomized trials.

(RCTs).

An extensive Medline, Embase and Cochrane search was performed. All placebo-controlled RCTs reporting data on TRT-related CV safety were considered. To better analyze the role of T on AF, population-based studies investigating the relationship between endogenous circulating T levels and AF incidence were also included and analyzed. The search, which accrued data from January 1, 1969 up to September 30th, 2023, was restricted to English-language articles and studies of human participants.

Out of 3.615, 106 studies were considered, including 8.126 subjects treated with TRT and 7.310 patients allocated to placebo. No difference between TRT and placebo were observed when major adverse CV events were considered. Whereas the incidence of non-fatal arrhythmias and AF was increased in the only trial considering CV safety as the primary endpoint, this was not confirmed when all other studies were considered (MH-OR 1.61[0.84;3.08] and 1.44[0.46;4.46]). Similarly, no relationship between endogenous T levels and AF incidence was observed after the adjustment for confounders.

Available data confirm that TRT is safe, and it is not related to an increased CV risk. Although non-fatal AF has been reported, the present meta-analysis does not confirm this preliminary finding.

none.