A Systematic Review of Studies Assessing Efficacy and Cardiovascular Safety of Testosterone Replacement Therapy in Men with Late-Onset Hypogonadism Due to Obesity ± Type 2 Diabetes Mellitus

Abstract

Background: There is a lack of consensus regarding efficacy and cardiovascular (CV) safety of testosterone-replacement therapy (TRT) in men with late-onset hypogonadism (LOH) secondary to obesity ±type 2 diabetes mellitus (T2DM). This is because of limited number of prospective randomized clinical trials (RCTs) in this cohort. Methods: A comprehensive retrospective review of medical literature was carried out using Preferred Reporting Items for Systematic Reviews and Meta-Analyses framework to assess the CV outcomes and safety of TRT in men with LOH. The review included scientific publications from January 2000 to July 2021, which included men with obesity ± T2DM. Results: Out of the 723 publications, which were identified on preliminary screening, 154 conformed to broad inclusion criteria for this systematic review of literature. Out of these 154 publications, 34 studies with a total number of 4,365,684 patients were finally included for this systematic review (9 randomized controlled trials, 6 meta-analyses and 19 observational studies). Studies investigating whether TRT offers protection against CV disease (CVD) and stroke generally concluded that the use of Testosterone (T) in middle-aged to elderly men has no detrimental impact on their CV risk. Older men with T2DM, obesity and metabolic syndrome are likely to benefit from TRT, as several studies point to an improvement in insulin sensitivity, markers of inflammation, time to Angina, CV risk, CV mortality, and even all-cause mortality. Conclusions: This retrospective systematic review of the literature, suggests modest efficacy of TRT in reducing major adverse cardiovascular events (MACEs) and all-cause mortality in men with LOH secondary to obesity and/or T2DM. TRT was associated with an increased risk of overall CVDs and MACE only when T preparations were given at supratherapeutic dosage or when TRT was offered to frail men. The findings of the current review could not confirm TRT as a cause of adverse CV events.