Gonadal-Hypothalamic Interaction in Prepubertal and Pubertal Man: Effect of Clomiphene Citrate on Urinary Follicle-Stimulating Hormone and Luteinizing Hormone and Plasma Testosterone

摘要

Extract: The effect of administering various doses of clomiphene citrate upon gonadotropin excretion and plasma testosterone in 13 prepubertal and 13 pubertal patients of both sexes was evaluated. Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were measured by the radioimmunoassay of urinary kaolin-acetone extracts. Clomiphene suppressed FSH excretion in two of five prepubertal patients given 0.1 mg/day for 1 week. There were neither stimulatory nor suppressive effects when 0.01 or 0.001 mg/day of the drug was administered.Urinary gonadotropins and plasma testosterone decreased when 100 mg/day of clomiphene were administered to early pubertal individuals. Neither stimulation nor suppression took place when 10 mg, 1 mg, or 0.1 mg/day were given to early pubertal patients. In two girls in midpuberty who received 100 mg/day of clomiphene, an LH rise was observed, and both of these individuals experienced menarche 17–24 days after the beginning of drug ingestion. Sequential studies in a boy between early and mid puberty revealed a change in gonadotropin and testosterone results from suppression to no response when 100 mg/day of clomiphene were given for 1 week.The data are consistent with the hypothesis that the hypothalamus of the early pubertal child is sensitive to negative feedback by the weak estrogen, clomiphene. Not until midpuberty can stimulatory effects of clomiphene, similar to those obtained in the adult, be demonstrated.Speculation: Presumably there is a marked change in the sensitivity of the hypothalamic-pituitary negative feedback centers to gonadal steroids during sexual maturation. Since the feedback set-point continues to decrease during puberty, the change in sensitivity may in fact begin early in childhood. Puberty might then be viewed as a continuum lasting several years, secondary sexual characteristics beginning only when a critical level of steadily increasing gonadotropin secretion is attained.