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Assessments of the Functional Capacity of the Gonadotrophs in Men: Effects of Estrogen and Clomiphene

Department of Reproductive Medicine, School of Medicine University of California, San Diego, Lajolla, California 92093

Correspondence to S. S. C. Yen.

Serum LH and FSH responses to serial injections of LRF with small (10 µg x 5), large (150 µg x 5), decremental (300 to 10 µg), and incremental (10 to 300 µg) doses at 2-hour intervals were assessed in eugonadal men. At constant doses, pulses of LRF induced pulsatile LH release which was qualitatively similar but quantitatively greater for the large than for the small dose of LRF. There were no periods of refractoriness or augmentation of subsequent responses from prior exposure to LRF when administered at 2-hour intervals. LH responses to incremental and decremental doses of LRF resulted in corresponding measurable changes in the magnitude of pituitary LH release. The FSH responses to pulses of LRF at all doses tested were uniformly small. These data suggest that analyses of the initial and integrated release (10 h experiment) to pulses of LRF may disclose the functional capacity of the gonadotrophs and that small variations in the endogenous LRF delivered may represent a significant factor in the control of LH release.

The small dose (10 µg x 5) of pulses of LRF was utilized in the assessment of estrogen and clomiphene treatments on the functional capacity of the gonadotrophs in normal men. Compared with the pretreatment results, both constant doses of ethinyl estradiol (50 µg/day x 7 days) and incremental doses of estradiol benzoate (100 to 400 µg, twice daily injections x 4 d) induced an attenuation of the initial release as well as of the integrated response (10 h) to pulses of LRF. Clomiphene treatment (100 mg/day x 5 d), likewise, resulted in a reduction of gonadotropin release to all pulses of LRF. These data suggest that circulating estrogen in intact men may have both a negative and a positive feedback effect on the gonadotrophs and that the testicular estrogen secretion as well as the extraglandular sources of estrogen, may play a critical role in the regulation of gonadotropin secretion in man.

Supported by Rockefeller Foundation Grant RF 75209. A portion of the patient studies was performed in the Clinical Research Center supported by NIH Research Grant RR00827.

¹ Former Research Fellow in Reproductive Endocrinology. Present Address: San Diego Zoo Hospital, P.O. Box 551, San Diego, California 92112.

² Former Research Fellow in Reproductive Endocrinology. Present Address: Department of Obstetrics and Gynecology, New York Hospital, Cornell Medical Center, 68th Street, New York, New York.

Received July 24, 1975.