Sex steroids and cardiovascular disease

• Published in: Asian journal of andrology Vol. 16; no. 2; pp. 239 - 247
• Main Author: Yeap, Bu Beng
• Format: Journal Article
• Language: English
• Published: China Medknow Publications and Media Pvt. Ltd 01-03-2014; Medknow Publications & Media Pvt. Ltd; Medknow Publications & Media Pvt Ltd; Wolters Kluwer Medknow Publications
• Subjects: Androgens; Atherosclerosis; atherosclerosis; cardiovascular disease; dihydrotestosterone; estradiol; mortality; testosterone; Cardiovascular disease; Cardiovascular diseases; Cardiovascular Diseases - physiopathology; Estradiol - physiology; Estrogens; Heart attacks; Hormone Replacement Therapy; Humans; Invited Review; Male; Mass spectrometry; Men; Mortality; Randomized Controlled Trials as Topic; Risk Factors; Steroids; Testosterone; Testosterone - administration & dosage; Testosterone - metabolism; Testosterone - physiology
• ISSN: 1008-682X; 1745-7262
• DOI: 10.4103/1008-682X.122357

As men grow older, testosterone (T) levels decline and the significance of this change is debated. The evidence supporting a causal role for lower circulating T, or its metabolites dihydrotestosterone (DHT) and estradiol, in the genesis of atherosclerosis and cardiovascular disease (CVD) in men is limited. Observational studies associate low baseline T levels with carotid atherosclerosis, aortic and peripheral vascular disease, and with the incidence of cardiovascular events and mortality. Studies using mass spectrometry suggest that when total T is assayed optimally, calculation of free T might not necessarily improve risk stratification. There is limited evidence to support an association of estradiol with CVD. Interventional studies of T therapy in men with coronary artery disease have shown beneficial effects on exercise-induced myocardial ischemia. However, placebo-controlled, randomized clinical trials (RCTs) of T therapy in men with the prespecified outcomes of cardiovascular events or deaths are lacking. Meta-analyses of randomized controlled trials of T published up to 2010 found no increase in cardiovascular events, mortality, or prostate cancer with therapy. Recently, in a trial of older men with mobility limitations, men randomized to receive a substantial dose of T reported cardiovascular adverse effects. This phenomenon was not reported from a comparable trial where men received a more conservative dose of T, suggesting a prudent approach should be adopted when considering therapy in frail older men with existing CVD. Adequately powered RCTs of T in middle-aged and older men are needed to clarify whether or not hormonal intervention would reduce the incidence of CVD.