Short- and Long-Term Effects of Clomiphene Citrate on the Pituitary-Testicular Axis

Abstract

Clomiphene citrate, administered to normal adult men, stimulates pituitary gonadotrophin secretion. It is useful in evaluating gonadotrophin reserve in hypogonadal patients with suspected hypothalamic-pituitary disease. Eight normal men received 100 mg of clomiphene daily for either 7 or 51 days during which time serum FSH, LH, and testosterone levels were measured. Mean serum FSH and LH titers increased 42% and 120% respectively, after seven days of clomiphene. Increase in serum LH levels ranged from 200–700% during the initial 21 days of clomiphene administration but then plateaued. Serum FSH levels exhibited a similar plateau after 35 days, with maximum titers 70–360% over control. The range in serum testosterone increments after 7 and 51 days of clomiphene administration was similar to that observed in serum gonadotrophin levels. The effect of clomiphene on gonadotrophin reserve was compared in twelve patients with hypogonadotrophic eunuchoidism, pituitary tumor, or “fertile eunuch” syndrome. The range of values for basal level of FSH in all patients, and LH in one patient, overlapped that for normal men. No patient with hypogonadotrophic eunuchoidism or “fertile eunuch” syndrome exhibited significant increments in serum FSH or LH levels, even after prolonged clomiphene administration. Similar to the response observed by others in prepubertal subjects, a paradoxical fall in serum FSH and LH occurred in all patients with hypogonadotrophic eunuchoidism in whom gonadotrophins were detectable. Therapeutic induction of sexual maturation did not alter this response to clomiphene. Serum LH or FSH did not significantly increase in four of five patients with pituitary tumor. In the fifth patient, a blunted increase in serum LH (26%) but not FSH was observed. Although histologic evaluation of germinal cell maturation revealed the effects of biologically active FSH in two patients with the “fertile eunuch” syndrome, FSH secretory reserve was diminished. Clomiphene stimulation is of value in discriminating normal subjects from patients with insufficiency of gonadotrophin reserve.