Androgen Deficiency

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Men with chronic renal failure exhibit features consistent with classical androgen deficiency: reproductive manifestations, including gynecomastia, impotence, testicular atrophy, impaired spermatogenesis, and infertility, as well as somatic disorders of bone, muscle, and other androgen responsive tissues (1,2). However, only a single well-controlled study has examined androgen replacement therapy in men with uremia (34). Nineteen men who were receiving regular hemodialysis were randomized to receive either oral testosterone undecanoate (240 mg/d) or placebo for 12 wk. Libido and sexual activity were increased, but hemoglobin was unchanged. There were no adverse clinical effects or hepatotoxicity. Effects on bone, muscle, cognition, and well-being were not reported. Further studies examining physiological androgen replacement therapy in men with chronic renal failure, notably using nonparenteral therapies in view of the increased bleeding risks in men with chronic renal failure, would be of great interest. Preliminary studies of transdermal testosterone patches demonstrate similar pharmacokinetics in uremic as in hypogonadal men (35).

A recent study evaluated pharmacological androgen therapy in receiving dialysis men. Twenty-nine men requiring regular hemodialysis were randomized to weekly im injections of nandrolone decanoate (100 mg, n = 14) or saline placebo (n = 15) for 6 mo in a study examining somatic and functional endpoints (36). Lean body (muscle) mass (measured by dual-energy x-ray absorptiometry) was increased and was associated with functional improvements as reflected by faster timed walking and stair climbing and a reduction in self-reported fatigue (37). Peak oxygen consumption was increased at 3 mo, but declined by the sixth month. Two of the three women receiving nandrolone required dose reduction because of virilization. Although the functional improvements in a well-controlled study were impressive, whether they are sustainable and improve survival remains to be evaluated. These encouraging findings suggest that larger, placebo-controlled clinical studies of longer duration to delineate the benefits and limitations of pharmacological androgen therapy in men with uremia would be of considerable interest.

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