Human Chorionic Gonadotropin and Testicular Function: Stimulation of Testosterone, Testosterone Precursors, and Sperm Production Despite High Estradiol Levels*

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Abstract
Excessive gonadotropin stimulation of the testis induced by the administration of high doses of hCG or LH markedly decreases testicular function in experimental animals. The adverse effects of supraphysiological gonadotropin stimulation are thought to be mediated, in part, by the very high levels of estradiol produced. We administered a supraphysiological dosage of hCG together with exogenous testosterone (T) to normal men for several months. The combination of these agents produced very high serum estradiol (E2) levels and (we assume) high intratesticular E2 levels. In this setting of supraphysiological gonadotropin stimulation and high E2 levels, we examined serum levels of T, the δ4 and δ5 steroid precursors of T, and sperm production. After a 3-month control period, five normal men received T enthanate (T; 200 mg, im, weekly) for 3–5 months. Then, while T was continued in the same dosage, all subjects were given hCG (5000 IU, im, three times weekly) for an additional 4–6 months. Serum E2 levels during hCG plus T treatment increased to a mean (±SEM) of 158 ± 16 pg/ml. Despite the very high E2 levels generated by this prolonged administration of hCG and T, hCG stimulated a mean increase of 5.1 ng/ml in the total T level and 0.18 ng/ml in the free T level over those found during T administration alone. These increments in T levels approximate normal blood T levels in man. Significant changes in serum levels of δ4 steroid precursors of T biosynthesis occurred during the study. Serum progesterone and 17-hydroxyprogesterone levels fell significantly with gonadotropic suppression induced by T administration alone and then increased significantly with hCG stimulation. In contrast to the changes seen in serum levels of δ4 precursors, there were no significant changes in levels of δ5 steroid precursors of T biosynthesis. An increased ratio of 17-hydroxyprogesterone to T during hCG administration was the only suggestion of an E2-induced block in steroid synthesis. hCG also significantly stimulated sperm production, as assessed by sperm concentration, motilities, and morphologies, in spite of the very high serum E2 levels; the mean sperm concentration increased from 1.0 ± 1.0 million/cc during T administration alone to 46 ± 16 million/cc during hCG plus T treatment. We conclude that chronic administration of supraphysiological dosages of hCG can stimulate testicular function in man, despite very high E2 levels, and that hCG in these dosages does not lead to severe testicular regression in man. Perhaps a higher dosage of hCG administered to men would replicate the severe testicular suppression reported in experimental animals. (J Clin Endocrinol Metab56: 720, 1983)

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