Differential effect of estrogen on pituitary responsiveness to GnRH in women with different forms of hypothalamic amenorrhea.

The effect of treatment with estradiol valerate (6 days, 2-6 mg/day) on basal levels of LH and FSH and on response of LH and FSH levels to GnRH challenge (2 X 25 micrograms GnRH, iv) were investigated in women with "hypothalamic amenorrhea", but without other endocrine disorders. Three groups were studied: 11 women with primary amenorrhea, 10 women exhibiting secondary amenorrhea related with weight loss, and 7 women with normal weight and with amenorrhea persisting after a period of severe weight loss. Before treatment with estradiol valerate the estradiol concentrations in all women were at the lower limit of the follicular phase of a normal ovulatory cycle. In addition, there were no differences between the groups in basal LH and FSH levels and in responses to GnRH challenges. Treatment with estradiol valerate suppressed the basal levels of FSH but not of LH in all women. Estradiol did not affect the response to GnRH challenge in women with primary amenorrhea, weakly augmented the response in women with secondary amenorrhea associated with weight loss, and strongly increased the response in secondary amenorrheic women who had regained normal weight. The results are interpreted in the light of the well-established fact that estrogen augments the gonadotropin response only if the pituitary gland is not exposed to high concentrations of GnRH. It is hypothesized that the differential response to GnRH of the present patients after estrogen treatment reflects differences in GnRH exposure of the pituitary gland, with patients with primary amenorrhea having the highest level of GnRH exposure.