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Chronic renal failure, dialysis, and transplantation cause major effects on male reproductive health, notably impairment of spermatogenesis, steroidogenesis, and sexual function, through effects at all levels of the hypothalamic-pituitary testicular axis. Delayed growth and puberty, sexual dysfunction, androgen deficiency, and infertility are the clinical consequences. This chapter reviews the basis and scope for various clinical applications of gonadotropin and androgen therapy as an adjunct to standard medical care of men with chronic renal failure. Androgen therapy is considered as either androgen replacement therapy (using testosterone doses equivalent to endogenous production rates aiming to restore but not exceed physiological testosterone exposure) or as pharmacological androgen therapy (using any androgen in doses optimized for efficacy, safety, and cost-effectiveness).

There is now convincing evidence that chronic renal failure is associated with a gonadotropin- and androgen-deficient state, providing a basis for evaluating the clinical use of androgen or gonadotropin replacement therapy. Various forms of gonadotropin therapy (estrogen blockade and gonadotropin administration) and of androgen replacement therapy have been little evaluated, so their risks and benefits remain to be clarified.

Pharmacological androgen therapy in chronic renal failure has a proven indication only for treatment of renal anemia, where it has been widely applied for more than three decades before being largely supplanted by recombinant human EPO. Although EPO is highly effective and widely used (including for women and children where androgens are best avoided), it is much more expensive. Recent studies suggest pharmacological androgen therapy is as effective as EPO in older men, and has synergistic, EPO dose- (and cost-) sparing effects in conjunction with low-dose EPO therapy. This suggests a diminished but continuing role of pharmacological androgen therapy for renal anemia. The potential for pharmacological androgen therapy to improve nutritional status and nonreproductive functions has long been considered, but the overall benefits on quality of life and survival remain to be well established. Such potential benefits would have to be weighed against potential adverse effects, including acceleration of cardiovascular or prostate disease and idiosyncratic androgen effects (poly-cythemia and sleep apnea).

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