Testosterone replacement therapy and the heart: friend, foe or bystander?

Abstract

The role of testosterone therapy (TTh) in cardiovascular disease (CVD) outcomes is still controversial, and it seems will remain inconclusive for the moment. An extensive body of literature has investigated the association of endogenous testosterone and use of TTh with CVD events including several meta-analyses. In some instances, a number of studies reported beneficial effects of TTh on CVD events and in other instances the body of literature reported detrimental effects or no effects at all. Yet, no review article has scrutinized this body of literature using the magnitude of associations and statistical significance reported from this relationship. We critically reviewed the previous and emerging body of literature that investigated the association of endogenous testosterone and use of TTh with CVD events (only fatal and nonfatal). These studies were divided into three groups, “beneficial (friendly use)”, “detrimental (foe)” and “no effects at all (bystander)”, based on their magnitude of associations and statistical significance from original research studies and meta-analyses of epidemiological studies and of randomized controlled trials (RCT’s). In this review article, the studies reporting a significant association of high levels of testosterone with a reduced risk of CVD events in original prospective studies and meta-analyses of cross-sectional and prospective studies seems to be more consistent. However, the number of meta-analyses of RCT’s does not provide a clear picture after we divided it into the beneficial, detrimental or no effects all groups using their magnitudes of association and statistical significance. From this review, we suggest that we need a study or number of studies that have the adequate power, epidemiological, and clinical data to provide a definitive conclusion on whether the effect of TTh on the natural history of CVD is real or not.

Double trouble: Co‐occurrence of testosterone deficiency and body fatness associated with all‐cause mortality in US men

“…Testosterone is linked to many physiologic effects, including improved sexual function, physical performance, muscle strength, lean body mass and cognitive function . Low levels of testosterone are associated with cardiovascular diseases, cancer and all‐cause mortality . Surprisingly, in the last decade, studies have shown that as many as 38.7% of men over 45 years old demonstrate low levels of testosterone (testosterone deficiency [TD]; total testosterone ≤350 ng/dL [12.15 nmol L −1 ]) .…”

Environment-wide association study to comprehensively test and validate associations between nutrition and lifestyle factors and testosterone deficiency: NHANES 1988–1994 and 1999–2004

“…Finally, there has been a small number of studies investigating the link between phosphorous and T levels. However, this link merits further scrutiny because high levels of phosphorous has been associated with a high risk of cardiovascular diseases [47], but low levels of T has been linked to a higher risk of cardiovascular disease [4,48]. A community dwelling study of 1,346 older men reported that high serum T levels were associated with lower serum phosphorus levels in a model adjusted for age, race and estradiol levels [49].…”

“…Testosterone (T) is linked with many physiologic effects, including improved sexual function, physical performance, muscle strength, lean body mass, cognitive function and an increased risk of cardiovascular mortality and morbidities [1][2][3]. Low levels of T is associated with cardiovascular diseases [4], cancer [5] and all-cause mortality [6]. In the United States alone, studies have reported that as many as 38.7% of men 45 years or older demonstrate low levels of T [7,8] or T deficiency (total testosterone ≤ 350 ng/dL) [9] with a projection that by 2025 approximately 6.5 million men will have T deficiency [8,10].…”

Effect of statins and testosterone replacement therapy on incident cardiovascular disease among male hormone-related cancer survivors

“… 21 In late 2013 and early 2014, two studies reported increased myocardial infarction and stroke associated with TTh use 22 , 23 ; however, other studies investigating the relationship between endogenous/exogenous testosterone and CVD in systematic reviews and meta-analysis of observational studies and randomized controlled trials found inconclusive results. 24 Of interest, there is a potential biological plausibility in the interaction between cholesterol and testosterone, and with their treatments, statins and TTh, because cholesterol is a required intermediate precursor in steroidogenesis. 25 – 27 Therefore, the objective of this study is to investigate the independent and joint associations of statins and TTh with CVD among HRCa survivors and a matched cancer-free cohort.…”