Potential benefits of T treatment in older men must be weighed against risks of adverse effects. In young hypogonadal men, physiological T replacement is low risk. In older men, risk–benefit ratios may be less advantageous. Minor adverse effects of T treatment include fluid retention, erythrocytosis, and sleep apnea, problems that may be more common in old men. Of greater concern are possible increases in atherosclerosis and greater risk of prostate cancer.
T treatment may lower HDL cholesterol and raise LDL cholesterol. Evidence indicates that excessive doses of anabolic steroids taken to build muscle mass may lead to premature coronary vascular disease (CVD). However, low T levels may also be associated with greater CVD risk. For example, in a study by Muller et al., free T levels in elderly men were directly related to rate of progression of common carotid artery intimal medial thickness, independent of cardiovascular risk factors. As noted previously, low T levels have also been associated with increased abdominal fat and insulin resistance and the metabolic syndrome. Finally, transdermal or injected T in men with low T levels may improve lipid pattern, reduce abdominal fat, decrease insulin resistance, lower triglycerides, and lead to more beneficial cardiac risk profile overall. Nonetheless, the net influence of exogenous T on atherosclerosis progression or incidence of CVD remains unknown.
The most worrisome issues with regard to T in older men are potential adverse effects on prostate cancer risk and benign prostatic hyperplasia (BPH). In a study in which elderly men were treated with T for 3 years, one treated group took T alone and the other T plus finasteride (F), a 5a-reductase inhibitor, given to block DHT production. PSA increased significantly in the T group, and prostate volume changes were smaller in the T plus F group. Effects of T on bone and muscle were similar in men treated with T or T plus F.
Novel pharmaceuticals called selective androgen receptor modulators (SARMs), which function as partial androgenic agonist/antagonists in prostate and seminal vesicle but full anabolic agonists in muscle and bone, may improve male anabolism but avoid potential effects on prostate disease. With regard to this putative risk, it is of note that most observational studies have failed to detect a significant association of endogenous T levels and prostate cancer incidence. Enlargement of the prostate and small increases in serum PSA have been observed in older men given exogenous T, without notable worsening of urinary tract symptoms or increased frequency of prostate cancer. However, in the absence of a large randomized trial of prostate effects of T, this question will remain a serious consideration.
