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

Abstract

Abstract. In order to clarify the age-related functional changes of the hypothalamic-pituitary-gonadal axis in men, the negative feedback control of serum gonadotrophin by sex steroids was studied in 39 young (18–34 years) and 49 elderly (62–95 years) men. Mean basal LH and FSH levels and the responsiveness to synthetic LRH were determined before and after daily im injection of testosterone propionate (TP; 5, 10 or 50 mg/day) or oestradiol benzoate (OeB; 50, 100 or 500 μg/day) for 3 days. After the administration of TP or OeB, serum levels of testosterone or oestradiol 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 μg/day of OeB. Responses of serum LH and FSH to LRH were inhibited significantly by TP at a dose of 50 mg/day and by OeB at doses of 100 and 500 μg/day. Whereas 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 μg OeB, serum LH response was decreased remarkably. Per cent suppression of serum LH response at 50 mg TP, as well as those of serum LH and FSH responses at 500 μg OeB in the elderly group, was significantly less than in the younger group. These data indicate that in the elderly men the regulatory system of gonadotrophin secretion appears to manifest a more marked resistance to inhibitory effects of sex steroids, and also suggest that the set-point to sex steroids in the hypothalamic-pituitary axis is reset at a higher level in male senescence.