Androgens in Health and Disease.pdf - E Library

Chapter 16/Androgen Treatment of the Hypogonadal Male 329
biopsy does not affect overall mortality, the potential medical, surgical, psychological,
socioeconomic, legal, and ethical consequences of this diagnosis may be great. Taking
these considerations into account, a recent consensus recommendation is that in older
hypogonadal men, a DRE and PSA level be monitored prior to starting therapy, shortly
after starting therapy (e.g., at 3–6 mo), and then yearly (7,84).
Because men have a higher risk of coronary artery disease than women and T administration
may suppress HDL cholesterol, leading to a more atherogenic lipid profile,
there is concern that T replacement in hypogonadal men will increase the risk of heart
disease. In severely androgen-deficient young men, T-replacement therapy decreases
HDL cholesterol concentration (85–88). In general, the degree of reduction in HDL
cholesterol is greater in more severely androgen-deficient men and with higher physiological
or supraphysiological T dosages, and it is much greater with nonaromatizable,
oral 17α-alkylated androgens (16). In contrast, T treatment of older mildly hypogonadal
men does not suppress HDL cholesterol, and total and LDL cholesterol are either not
affected or decreased (7). The clinical significance of these T-induced lipoprotein
changes on cardiovascular risk is not known. Furthermore, most cross-sectional epidemiological
studies suggest that low T levels are associated with an increase in the risk
and severity of coronary artery disease, and longitudinal studies fail to find a relationship
between T levels and development of coronary heart disease (7,83,89,90). Also,
intervention studies suggest that T treatment may improve exercise-induced coronary
ischemia and angina (91–97). However, long-term controlled studies are needed to
determine the effects of T treatment on major cardiovascular outcomes, such as the
incidence of coronary death, myocardial infarction, and stroke. At present, cardiovascular
health and plasma lipids should be evaluated as dictated by general practices, and
more intensive monitoring is not justified.
Potentially serious hepatotoxicity occurs predominantly with the use of oral 17αalkylated
androgens, and rarely, if ever, occurs with the use of injectable T esters or
transdermal T formulations (16). Routine testing of liver enzymes is not necessary
with the use of the latter preparations for androgen replacement in hypogonadal men.
By suppressing endogenous gonadotropin production, T treatment reversibly suppresses
spermatogenesis to varying degrees, depending on the T formulation, dosage,
and duration of treatment, underlying etiology of hypogonadism, and baseline spermatogenesis
(2). The suppression of sperm production may further impair fertility in
hypogonadal men receiving androgen therapy. This effect of T therapy is usually only
clinically relevant in men with hypogonadotropic hypogonadism with otherwise normal
testes. In gonadotropin-deficient men, if fertility is desired, androgen therapy should
be discontinued and gonadotropin treatment should be started initially with human
chorionic gonadotropin (hCG) and then, if necessary, with combined hCG and human
menopausal gonadotropin (hMG) or hFSH administration (2). In the absence of concomitant
testicular disease (e.g., cryptorchidism), previous T-replacement therapy does
not impair the subsequent induction of spermatogenesis with gonadotropin therapy.
Occasionally, local discomfort or bleeding may occur at the site of T ester injections.
Using proper intramuscular injection techniques may minimize these side effects.
Administration of T esters subcutaneously usually causes severe local irritation and
pain. Rarely, patients may experience an allergic reaction to the injection vehicle,
sesame oil (T enanthate), or cottonseed oil (T cypionate). As discussed previously,
transdermal T patches may cause local skin irritation, itching, contact dermatitis, and,