Studies on the Role of Sex Steroids in the Feedback Control of Gonadotropin Concentrations in Men. III. Androgen Resistance in Primary Gonadal Failure

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Abstract
The negative feedback control of serum gonadotropins by sex steroids was studied in eight men with Leydig cell insufficiency, four of whom had diminished and four with unmeasurable Leydig cell function. Mean serum LH and FSH concentrations, the pattern of LH pulsatile release, and the response of gonadotropins to LRH stimulation were studied before and at the completion of 4-day continuous infusions of testosterone (T; 15 mg/day), 17/S-estradiol (E; 90 μg/day), and 5a-dihydrotestosterone (DHT; 7.0 mg/day). Both T and E infusion resulted in approximately 30% suppression of mean serum LH and FSH concentrations in hypogonadal subjects; these responses were similar to those of normal men. Neither T nor E infusion produced a decrease in LH pulse frequency or amplitude in hypogonadal men. This differs from the decrease in LH pulse frequency seen with T and the fall in LH pulse amplitude during E infusion previously observed in normal men. The fall in mean serum LH concentration during infusion of the nonaromatizable androgen DHT was significantly less in the hypogonadal (11 ± 2.7%) than in the normal men (35 ± 10%; P > 0.05). DHT resulted in an augmentation of the LH response to LRH administration in normal men, which was not observed in the hypogonadal men. No significant FSH suppression by DHT was seen in either group. The data indicate that the modulation of LH by sex steroids in men with primary hypogonadism appears to differ from normal in that there is a resistance to the effects of pure androgen. The mechanism for this resistance remains to be determined. (J Clin Endocrinol Metab48: 553, 1979)