Differential Responsiveness to LRF after Estrogen Therapy in Women with Hypothalamic Amenorrhea

Abstract

Ten amenorrheic and eight normally cycling women were challenged with a 10-jug doseof synthetic LRF before and after a short 3- to 5-day course of ethinyl estradiol (1.0–1.5 /µg/kg/day). In normally cycling women tested on day 5 of the menstrual cycle, significant augmentation of the LRF-induced LH but not FSH response was observed after estradiol treatment. The amenorrheic patients all had normal or reduced levels of serum gonadotropins, no evidence of galactorrhea, and no other endocrine abnormality. Responses to LRF inthe amenorrheic women were easily segregated into two groups after treatment with estrogen: those with significantly augmented LH response (P < 0.05) and others with markedly diminishedresponses (P < 0.005) when compared with responses to LRF before estrogen treatment. The response patterns for FSH were similar although not so pronounced. That group of amenorrheic women with augmented LRF-induced LH response had peripheral estradiol concentrations of 15 pg/ml or more and responded to clomiphene citrate with a doubling in serum gonadotropin levels. The five women with diminished LRF-induced gonadotropin response had essentially undetectable circulating levels of serum estradiol (<15 pg/ml). The differential LRF-induced responses observed in this study suggest that gonadal steroids may exert a direct effect on gonadotrophs in terms of both the dose and duration of exposure. Moreover, although these data suggest that patients with hypothalamic amenorrhea may be subdivided into two groups, there is some evidence that such patients may represent a continuum from minimal hypothalamic dysfunction to a frankly unresponsive hypothalamic-pituitary axis.