Serum LH and FSH responses to synthetic gonadotropin-releasing hormone in normal men.

The effects of dose and of age on the serum LH and FSH responses to synthetic gonadotropin-releasing hormone (GnRH) were determined in normal men. GnRH was given as in iv bolus in doses from 2 to 500 mug to each of nine normal men, 20-39 years old. The mean (+/- SE) maximum delta LH (maximum increment above the basal concentration) in response to each dose of GnRH was 2 mug, 7.2 +/- 1.7 mIU/ml; 10 mug, 15.7 +/- 3.4 mIU/ml; 50 mug, 37.7 +/- 9.6 mIU/ml; 250 mug, 47.8 +/- 11.2 mIU/ml; and 500 mug, 49.3 +/- 11.2 mIU/ml. The mean delta FSH in response to each dose was 2 mug, 0.5 +/- 0.2 mIU/ml; 10 mug, 0.8 +/- 0.2 mIU/ml; 50 mug, 1.2 +/- 0.3 mIU/ml; 250 mug, 2.0 +/- 0.3 mIU/ml; and 500 mug, 2.4 +/- 0.4 mIU/ml. Since both the LH and FSH responses to the 250 mug dose were significantly greater than those to smaller doses, but the responses to the 500 mug dose were not still larger, 250 mug was used as the standard test done for subsequent studies. The effect of age was tested by administering a 250 mug dose of GnRH as an iv bolus to 42 carefully selected normal men, 14 in each of three age groups, 20-39, 40-59, and 60-79 years old. Dialyzable serum testosterone levels decreased with increasing age, from 21.7 +/- 4.6 to 16.0 +/- 4.9 to 14.3 +/- 3.8 ng/dl (mean +/- SD), and the basal serum LH levels increased slightly, from 7.4 +/- 3.4 to 9.6 +/- 3.1 to 10.8 +/- 3.2 mIU/ml, suggesting that a slight degree of primary Leydig cell failure occurs with increasing age. There was no corresponding increase in mean maximum delta LH in response to GnRH with increasing age, despite the elevation in mean basal LH levels. The maximum delta LH/basal LH ratio, in fact, declined from 6.8 to 5.1 to 3.3 in the three age groups. The basal serum FSH levels did not change with increasing age, but the mean delta FSH values decreased from 3.0 +/- 0.5 to 2.9 +/- 1.1 +/- 0.3 mIU/ml. These data demonstrate decreased LH and FSH responses to synthetic GnRH, as well as some primary Leydig cell failure, in the male senescence.