After subcutaneous administration of 14 C-nafarelin acetate to men, 44–55% of the dose was recovered in urine and –% was recovered in feces. Approximately 3% of the administered dose appeared as unchanged nafarelin in urine. The 14C serum half-life of the metabolites was about hours. Six metabolites of nafarelin have been identified of which the major metabolite is Tyr-D(2)-Nal-Leu-Arg-Pro-Gly-NH2(5-10). The activity of the metabolites, the metabolism of nafarelin by nasal mucosa , and the pharmacoki netics of the drug in hepatically- and renally-impaired patients have not been determined.
Decreased sperm count and motility were seen in infertile subjects. Serum T and LH levels, as well as seminal plasma and blood levels of dopamine, adrenaline, and noradrenaline were also decreased in all groups of infertile men. This was accompanied by significantly increased serum FSH and PRL levels in oligozoospermic subjects. Treatment with M. pruriens significantly improved T, LH, dopamine, adrenaline, and noradrenaline levels in infertile men and reduced levels of FSH and PRL. Sperm count and motility were significantly recovered in infertile men after treatment.
The physiology of the reproductive system changes dramatically with the onset of major illness. The serum testosterone concentrations fall to pre-pubertal levels secondary to a decreased secretion of gonadotropins and a decreased Leydig cell response to luteinizing hormone. At the same time, the serum oestrogen concentration rises as the result of an increased rate of peripheral aromatization. The clinical consequences of these marked changes are not yet well understood. One line of evidence argues for the administration of anabolic steroids (derivatives of testosterone) to critically ill patients to improve their catabolic state. Another line of evidence in animal models suggests that testosterone may suppress the immune system and myocardial function in critical illness. No clinical trials of oestrogen administration to critically ill patients have been reported, although two animal studies suggest that oestrogen may have a positive effect on survival. This chapter reviews changes in the physiology of the reproductive system in major illness as well as current evidence regarding the clinical effects of androgens and oestrogens in critical illness and their potential therapeutic roles.