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Studies on the Role of Sex Steroids in the Feedback Control of Gonadotropin Concentrations in Men. II. Use of the Estrogen Antagonist, Clomiphene Citrate^*

Developmental Endocrinology Section, Endocrinology and Reproduction Research Branch, National Institute of Child Health and Human Development, National Institutes of Health Bethesda, Maryland 20014

Address requests for reprints to: Richard J. Sherins, M.D., Developmental Endocrinology Section, Endocrinology and Reproduction Research Branch, National Institute of Child Health and Human Development, Building 10, Room 10B09, Bethesda, Maryland 20014.

To further evaluate the relative roles for androgen and estrogen in the feedback regulation of gonadotropin secretion in men, we studied the effects of sex steroids on serum LH and FSH concentrations, the pulsatile release of LH, and the responses of LH and FSH to LRH administration before and during chronic clomiphene administration. We theorized that this approach might provide an opportunity to evaluate the pure androgenic component of testosterone, independent of its aromatization to estradiol, since the estrogen antagonist, clomiphene, would block estrogen-mediated effects.

Infusion of testosterone (T; 7.5 mg/day for 4 days) produced a 40% decline in serum LH and FSH concentrations. Estradiol (E) infusion in dosages equivalent to that derived from the infused T (45 µg/day) resulted in a decline in serum LH which was 60% of that seen with T, indicating that most of the Tmediated LH suppression could be attributed to its aromatization to E. Dihydrotestosterone infusion also resulted in a 35% decrease in mean serum LH and a decrease in the number of spontaneous LH pulses similar to that seen with T, supporting a role for a pure androgenic component in T-mediated LH suppression.

During chronic clomiphene therapy, neither T nor E when given in doses equal to twice their mean production rate in normal men, nor the nonaromatizable androgens, dihydrotestosterone and fluoxymesterone, in dosages equipotent to the infused T were capable of suppressing serum LH or FSH levels or altering the responses of LH and FSH to LRH administration. The resistance of gonadotropin to suppression by androgen during clomiphene blockade remains unexplained. (J Clin Endocrinol Metab 48: 222, 1979)

^* This study was presented in part at the 58th Annual Meeting of The Endocrine Society, San Francisco, June 1976.

Received February 21, 1978.

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