Sexual function is frequently impaired by chronic renal failure (55) and is only partly reversed by transplantation, although few well-controlled studies are available. Contributory factors include vascular failure, pelvic autonomic neuropathy, antihypertensives (particularly centrally acting agents and beta blockers), and other medications, together with additive effects of age, depression, and general debility. Uremic sexual function is not consistently improved with androgen therapy (200-400 mg testosterone enanthate weekly) (56-58). Other proposed treatments, such as zinc supplementation (59), pro-lactin-lowering with bromocryptine (60), and tricyclic antidepressants (61), are equally inconsistent. Oral vitamin E supplementation (300 mg/d for 8 wk) improved self-reported sexual function (libido, erectile activity, and coitus) in a balanced randomized, double-blind, placebo-controlled study of 24 men with uremia (62). The modest improvement was not associated with significant changes in reproductive hormones and, if reproducible, further studies, including dose optimization, may be worthwhile.
General debility (including anemia) may have a significant role in causation of uremic sexual dysfunction, because recombinant human EPO therapy improves reproductive function. Menstrual and male sexual function were significantly improved and blood prolactin concentrations lowered in a study that randomized 44 patients on dialysis to standard treatment with EPO (180 U/kg/wk) or no treatment (63). Other cross-sectional (64) and uncontrolled studies (65-67) corroborate these findings. Nevertheless, EPO does not improve the sexual dysfunction of men with impaired renal function who do not requiring dialysis (65). EPO administration reduces the endocrine abnormalities in men with uremia with lowering of the exaggerated basal and GnRH-stimulated LH and FSH concentrations and increases in blood testosterone concentrations (67-69). Whether this is a specific effect of EPO or is mediated via general effects, such as improvement in anemia and nutritional status, remains to be clarified.
There is increasing experience applying the recent advances in the management of erectile dysfunction, notably pharmacotherapy and mechanical devices, to men with chronic renal failure. For men with chronic renal failure complaining of erectile dysfunction, the management involves initially optimizing conventional medical treatment for uremia, including intensive dialysis or transplantation, nutritional support (including raising hemoglobin), and medication review (70). The first line of specific therapy is oral sildenafil (71), which appears significantly better than placebo in a preliminary report of a randomized, placebo-controlled study (72), which extends similar positive experience from uncontrolled studies of men on dialysis (73,74). However, particular vigilance with sildenafil usage is required for men with chronic renal failure in view of their accelerated rates of atherogenesis. Sildenafil is absolutely contraindicated in men using nitrates for coronary artery disease (where lethal hypotension can occur), and caution is also required in men with complex antihypertensive regimes. If sildenafil is not effective or is contraindicated, additional options include mechanical devices (vacuum/constriction devices or implantable prosthesis) or cavernosal vasodilator pharma-cotherapy (prostaglandin E and phentolamine, papaverine, and mixtures). One study found high rates of satisfaction with a vacuum device in a selected subset of impotent men on dialysis (56), but these devices are most useful in men with only partial erectile dysfunction. Surgically implanted hydraulic cavernosal prostheses are an expensive last resort, with significant risks of mechanical failure and infection, especially in immunocompromised transplant patients. Vasodilator therapy is most effective when injected intracavernosally (75), but involves significant safety concerns requiring careful monitoring, including the risks of priapism, bleeding, thrombosis, or hypertension; nevertheless, some preliminary experience is encouraging (76,77). Transurethral application of prostaglandin E (78) has theoretical safety advantages over intracaver-nosal injection but has limited efficacy.
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