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Testosterone does not appear to increase the risk of developing prostate cancer. Adult testosterone effects are more clearly demonstrable in males than in females, but are likely important to both sexes. Both testosterone and DHT bind to an androgen receptor; however, DHT has a stronger binding affinity than testosterone and may have more androgenic effect in certain tissues at lower levels. Since testosterone levels decrease as men age, testosterone is sometimes used in older men to counteract this deficiency. In addition to its role as a natural hormone, testosterone is used as a medication to treat hypogonadism and breast cancer. On average, in adult males, levels of testosterone are about seven to eight times as great as in adult females. The U.S. FDA recommends that all T supplements carry a warning that they may increase the risk of heart attack and stroke.
Pubertal effects begin to occur when androgen has been higher than normal adult female levels for months or years. For postnatal effects in both males and females, these are mostly dependent on the levels and duration of circulating free testosterone. The eligibility criteria for this analysis included all placebo-controlled studies that enrolled men (1) with low or low-normal testosterone levels, and (2) who received any testosterone formulation for ≥ 3 months. They concluded that TRT for hypogonadism does not appear to increase PSA or the risk of prostate cancer. No significant adverse CV events were noted.28 Further studies are needed to evaluate the clinical effects of TRT in CHF, but testosterone appears to be a promising therapeutic option for patients with CHF. No definitive statement can be made regarding the effects of testosterone replacement therapy on the levels of either LDL or HDL cholesterol.11 Interpretation of total T concentrations is confounded by variation between individuals, variation in serum SHBG, and variation in androgen sensitivity.6 Furthermore, considerable controversy has arisen regarding the accuracy of currently available commercial testosterone assays, especially those showing T levels at the lower end of the "normal" range.4 Free testosterone level may be a more reliable indicator of androgen status, but more studies are needed to confirm this.
Not only do hypogonadal men exhibit lower levels of endothelial progenitor cells, but these cells appear to increase in proliferation and migration in an AR-dependent manner.69 Some observational studies, including one by Mäkinen et al.,67 have reported inverse correlations between testosterone and intima-media thickness, a surrogate marker for atherosclerosis. It is important to note that these findings oppose those of other studies reporting that testosterone intensifies vasocontraction.64 Since these advisories were issued, additional observational studies have been conducted to assess the impact of ADT on cardiovascular outcomes. In the same year, however, D'Amico et al.47 pooled data from 3 RCTs examining short-term androgen suppression therapy and found that older men who received androgen suppression therapy had shorter times to fatal myocardial infarctions than those who did not receive therapy. Prostate cancer is the second most frequent malignancy in men worldwide.4 In 1941, Huggins and Hodges37 were the first to demonstrate the beneficial effects of castration and estrogen injections in men with metastatic prostate cancer. Further, many studies conducted only a single testosterone measurement, which may have been impacted by significant diurnal variation.22 Most studies also did not consider the clinical presentation of testosterone deficiency.
Among the subjects with elevated hematocrit, there was only one incident of serious complication (cerebral hemorrhage).34 The most recent meta-analysis examining the adverse effects of TRT was performed by Fernandez-Balsells et al. in 2010. In this study, fat biopsies were also used to show that the expression of insulin-signaling genes (IR-ß, IRS-1, AKT-2, and GLUT 4) was lower in men with TD and diabetes. Although T was shown to significantly improve exercise capacity, none of the studies found a significant change in LVEF, although NYHA class was shown to improve in two of the studies.
Studies of men who abuse anabolic steroids have clearly demonstrated higher risk of myocardial infarction and sudden cardiac death.10, 11, 12 In men, exogenous oestrogen therapy has also been trialled for secondary prevention of coronary disease, following acute myocardial infarction.13 This trial was terminated early due to a twofold increase in re-infarction and a significant increase in mortality. The article concludes with a discussion regarding the future direction for work in this interesting area, including the relative merits of screening for, and treating hypogonadism with testosterone replacement therapy in men with heart disease. Despite regional variations in the prevalence of coronary artery disease (CAD), men are consistently more at risk of developing and dying from CAD than women, and the gender-specific effects of sex hormones are implicated in this inequality. Although cross-sectional studies have demonstrated higher prevalence of CVD among men with low endogenous androgens, limited clinical data have not shown that testosterone replacement therapy (TRT) reduces CVD risk.
Replacing testosterone in men is simple, cheap and easy to monitor both clinically and biochemically. However, continuing benefit was observed with therapy up to 9 months in the case of improvements in blood pressure, 12 months in the case of improved glycamemic control and up to 2 years in the case of improved lipid profiles. When compared to baseline and a placebo, time to ischaemia was significantly prolonged after intravenous testosterone.
Ruige et al.21 reported a weak pooled protective effect of total testosterone on CVD in healthy men. Some systematic reviews and meta-analyses have suggested that the conflicting associations, and subsequent lack of firm conclusions, may be due to study heterogeneity and low-quality evidence. Testosterone and DHT bind to the androgen receptor (AR) to regulate androgen-responsive genes. Testosterone can be converted to dihydrotestosterone (DHT) or 17β-estradiol (E2). HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; QTc interval, heart-rate–corrected QT interval; RBC, red blood cell.