Testosterone and secondary hypertension: new pieces to the puzzle.

The absence of estrogen, in males or after menopause in women, is independently associated with increased cardiovascular risk. A number of factors have been implicated as the underlying cause, including effects at the cell-organ level (eg, inflammatory activation, increased oxidative stress, and increased vasoconstriction), as well as changes in cardiovascular physiology (eg, sympathetic activation, increased blood pressure, and insulin resistance). All of these parameters are sensitive to modulation by sex steroid hormones, particularly 17 -estradiol, testosterone, and its more active metabolite, 5 -dihydrotestosterone, which is produced from testosterone by 5 -reductase. Testosterone is the main male sex steroid hormone but is also produced by women. Testosterone is converted to 17 -estradiol by aromatase in numerous tissues, including the vasculature and adipose tissue, representing an important local source of estrogen. In obesity, aromatase-derived 17 -estradiol formation may represent an important cause of feminization in males and the increased risk of estrogensensitive cancers in obese females. Androgenic Steroids and Cardiovascular Risk In many countries, including the United Kingdom, the United States, Canada, and Australia, anabolic androgenic steroids, such as testosterone, are controlled substances, and their nonmedical use is considered drug abuse. Testosterone has been used since the 1930s for nonmedical, athletic purposes, especially in male and female body builders and swimmers. Because testosterone abuse may increase arterial blood pressure, leading to left ventricular hypertrophy, it should be included among the differential diagnoses of secondary arterial hypertension. Moreover, testosterone abuse has been associated with myocardial infarction because of coronary vasospasm or thrombosis. Among the mechanisms of how exogenous, as opposed to endogenous, testosterone contributes to increased in cardiovascular risk, coagulatory activation, as well as accelerated progression of coronary artery disease, have been described. Sex steroids dilate human coronary arteries, and diminished vasodilator activity in response to testosterone under hypertensive conditions has been reported, yet research into the mechanisms of testosterone’s contribution to or aggravation of hypertension, particularly in the presence of genetic risk, remains scarce.