Age-related changes in the feedback regulation of gonadotrophin secretion by sex steroids in men

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Abstract
To clarify the age-related functional changes of the hypothalamic-pituitary-gonadal axis in men, the negative feedback control of serum gonadotropin by sex steroids was studied in 39 young (18-34 yr) and 49 elderly (62-95 yr) men. Mean basal LH [lutropin] and FSH [follitropin] levels and the responsiveness to synthetic LRH [luliberin] were determined before and after daily i.m. injection of testosterone propionate (TP; 5, 10 or 50 mg/day) or estradiol benzoate (EB; 50, 100 or 500 .mu.g/day) for 3 days. After the administration of TP or EB, serum levels of testosterone or estradiol were more elevated in the elderly than in the younger group. In the latter, basal LH level decreased significantly at 10 mg/day of TP and so did basal levels of both LH and FSH at 50 and 100 .mu.g/day of EB. Responses of serum LH and FSH to LRH were inhibited significantly by TP at a dose of 50 mg/day and by EB at doses of 100 and 500 .mu.g/day. In the elderly group, basal LH levels and responses of both LH and FSH were not suppressed significantly by TP regardless of the dose. At a dose of 500 .mu.g EB, serum LH response was decreased remarkably. Percent suppression of serum LH response at 50 mg TP and that of serum LH and FSH responses at 500 .mu.g EB in the elderly group were significantly less than in the younger group. In the elderly men the regulatory system of gonadotropin secretion appears to manifest a more marked resistance to inhibitory effects of sex steroids, and the set-point to sex steroids in the hypothalamic-pituitary axis is reset at a higher level in male senescence.

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