Testosterone-Induced Inhibition of the LH and FSH Responses to Gonadotropin-Releasing Hormone Occurs Slowly

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Abstract
To quantitate the inhibitory effect of a prolonged increase in serum testosterone concentration on the serum LH and FSH concentrations in men, testosterone enanthate was administered every seven days for eight doses to 12 normal men and to seven men with primary hypogonadism. Serum testosterone and estradiol concentrations were measured on days 0 to 7, 14, 21, 28, 35, 42, 49 to 56, and 84. Serum LH and FSH concentrations, both basal and in response to gonadotropin-releasing hormone (GnRH), were measured on days 0, 7, 14, 28, 56, and 84. In six normal men who received 50 mg of testosterone enanthate every seven days, the mean (±SE) serum testosterone concentration increased from 572 ± 98 ng/dl on day 0 to an average of 768 ± 87 ng/dl on days 1 to 7 (P < 0.05), and was maintained at an average of 810 ± 137 ng/dl on days 50 to 56. Serum estradiol concentrations did not change during the time of testosterone administration. The mean (±SE) LH response area following GnRH decreased from 6670 ± 753 mlU-min/ml on day 0 to 4482 ± 240 mlU-min/ml (P < 0.025) by day 28, but the mean basal LH and FSH concentrations and the mean FSH response area did not change. In six normal men who received 200 mg of testosterone enanthate every seven days, the mean serum testosterone concentration increased from 507 ± 53 ng/dl on day 0 to an average of 1199 ± 86 ng/dl (P < 0.001) on days 1 to 7, and was maintained at an average of 1333 ± 144 ng/dl, on days 50 to 56. By thin-layer chromatography, unhydrolyzed testosterone enanthate was found to make no detectable contribution to the measured testosterone levels in these men. The mean serum estradiol concentration increased from 26 ± 1 pg/ml on day 0 to an average of 39 ± 4 pg/ml (P < 0.05) on days 1-7 and to 60 ± 18 (P < 0.001) on days 49-56. The basal LH concentration was 8.8 ± 1.3 mlU/ml on day 0, had decreased significantly by day 14, and by day 56 was 4.9 ± 0.5 mlU/ml (P < 0.01). The LH response area was 5955 ± 558 mlU-min/ml on day 0, was not significantly reduced until day 28, but by day 56 was virtually obliterated, 247 ± 125 mlU-min/ml. The basal serum FSH concentration had decreased by day 14, but the FSH response area did not decrease until day 28. In the seven men with primary hypogonadism, who received 200 mg of testosterone enanthate every seven days, die mean serum testosterone concentration increased from 184 ± 53 ng/dl on day 0 to an average of 1033 ± 346 ng/dl (P < 0.01) on days 1 to 7, and was maintained at an average of 1132 ± 260 ng/dl on days 50 to 56. The mean serum estradiol concentration almost tripled during this time. The basal LH and FSH concentrations and the mean LH and FSH response areas all decreased markedly during the treatment period, but even by day 56 one man still had supranormal basal LH and FSH concentrations, and three men had normal or supranormal LH and/or FSH responses to GnRH. We conclude that, in order to inhibit markedly the LH and FSH responses to synthetic GnRH, the serum testosterone concentration must be raised to 150% above the mean normal level for 28 days in normal men and for 28 to 56 days or longer in men with primary hypogonadism.