The Dark Side of Testosterone Deficiency: III. Cardiovascular Disease

Abstract

A considerable body of evidence exists suggesting that androgen deficiency contributes to the onset, progression, or both of cardiovascular disease (CVD). The aim of this review is to evaluate the relationships between testosterone (T) deficiency and risk factors of CVD and to discuss the implications of androgen deficiency in men with cardiovascular risk factors. The relationship between androgen deficiency and endothelial function, lipid profiles, inflammatory responses, altered vascular smooth muscle reactivity, and hypertension are discussed with regard to CVD. A comprehensive literature search was carried out with the use of Pub Med from 1980 through 2009, and relevant articles pertinent to androgen deficiency and vascular disease were evaluated and discussed. Low T, whether attributed to hypogonadism or androgen deprivation therapy, in men with prostate carcinoma, produces adverse effects on cardiovascular health. Androgen deficiency is associated with increased levels of total cholesterol, low-density lipoprotein, increased production of proinflammatory factors, and increased thickness of the arterial wall and contributes to endothelial dysfunction. Testosterone supplementation restores arterial vasoreactivity; reduces proinflammatory cytokines, total cholesterol, and triglyceride levels; and improves endothelial function but also might reduce high-density lipoprotein levels. Testosterone is an anabolic hormone with a wide range of beneficial effects on men's health. The therapeutic role of T in men's health, however, remains a hotly debated issue for a number of reasons, including the purported risk of prostate cancer. In view of the emerging evidence suggesting that androgen deficiency is a risk factor for CVD, androgen replacement therapy could potentially reduce CVD risk in hypogonadal men. It should be emphasized, however, that androgen replacement therapy should be done with very thorough and careful monitoring for prostate diseases.

Welcoming low testosterone as a cardiovascular risk factor

“…Recent studies also suggest a beneficial role for testosterone in endothelial regeneration. 26 Testosterone replacement in hypogonadal men results in an increase in the number of circulating endothelial progenitor cells. 27 This increase is androgen receptor mediated (not a result of rise in estrogen levels) as this event is abolished by androgen receptor antagonists.…”

Hypertension, dyslipidemia and overweight are related to lower testosterone levels in a cohort of men undergoing prostate biopsy

“…Consequently, testosterone determination is mandatory in the differential diagnosis of male impotence. 5 Testosterone level is related to other entities not related with the sexual sphere such as diabetes mellitus (DM), 6 metabolic syndrome (MS), 7 heart disease 8 and even mortality. 9 MS is a cluster of risk factors that includes abdominal obesity, increased blood fasting glucose, dyslipidemia and hypertension.…”

Regulated expression of the prostacyclin receptor (IP) gene by androgens within the vasculature: Combined role for androgens and serum cholesterol

“…While the role of testosterone and other androgens in CVD risk in men is controversial [49,50], recent clinical, epidemiological, cellular and animal studies have demonstrated that similar to the protective effects of E2 in women, androgens can also have positive effects on the vasculature [25,31,34,51,52]. This is exemplified by the increased incidence of CV risk factors in men with hypogonadism or undergoing androgen deprivation therapy (ADT) as part of their treatment regimen for prostate cancer [28][29][30].…”