Androgens and Cardiovascular Disease in Men

Review
In: Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000.
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Excerpt

Testosterone is the principal male sex hormone or androgen, which regulates sexual characteristics and body composition. Testosterone is converted to bioactive metabolites dihydrotestosterone and estradiol. Circulating testosterone peaks in early adulthood and declines gradually across middle and older age: older men exhibit lower testosterone and dihydrotestosterone concentrations compared to younger men. In older men, lower testosterone concentrations are associated with higher incidence of cardiovascular events. Lower testosterone and dihydrotestosterone concentrations have also been associated with higher cardiovascular mortality in older men. However, causation is unproven as a randomized placebo-controlled trial of testosterone treatment sufficiently powered to examine outcomes of cardiovascular events or mortality has yet to be reported. Potential mechanisms by which testosterone could exert beneficial actions in the vasculature include reduction in cholesterol accumulation and modulation of inflammation. Smaller randomized trials of testosterone therapy have shown improvements in surrogate endpoints related to cardiovascular risk. However, other trials of testosterone have not shown improvements in carotid atherosclerosis, as assessed by carotid intima-media thickness. One study reported an increase in coronary atheroma assessed using coronary computed tomography angiography in older men receiving testosterone therapy over 12 months. Although one randomized trial of testosterone therapy in older men with mobility limitations reported an excess of adverse events in the treatment arm, larger recent trials in middle-aged to older men did not find any excess of cardiovascular adverse events with testosterone treatment. Meta-analyses of testosterone trials generally have not shown an increase in cardiovascular adverse events. Retrospective case-control studies of health insurance databases have major methodological limitations. The results from such studies are inconsistent, associating testosterone prescriptions with either increased or decreased risk of cardiovascular events, and with lower mortality. While androgen deprivation in men with prostate cancer results in adverse metabolic effects, abuse of high dosages of androgenic steroids is associated with harm. Thus, while some epidemiological studies associate higher circulating concentrations (but within the normal range) of endogenous androgens with lower risk of cardiovascular events and mortality, the effects of exogenous androgens in the form of testosterone therapy seeking to maintain physiological circulating androgen concentrations on the cardiovascular system remain uncertain. This evidence gap has to be accommodated in the current clinical management of hypogonadal men and should be addressed by further randomized interventional studies to clarify whether testosterone treatment has beneficial, neutral or adverse effects on the cardiovascular system. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.

Publication types

  • Review