Hypothalamic Amenorrhea and Hypogonadotropinism: Responses to Synthetic LRF

The gonadotropin releasing mechanism was found to be defective in a selected group of patients with hypogonadotropic secondary amenorrhea and otherwise normal pituitary function. When compared with the low estrogen phase of the normal cycle (early follicular phase), circulating LH and estradiol levels were significantly lowered and the pulsatile fluctuation of LH was typically absent. Although circulating FSH was at a comparable level, the expected negative feedback relationship between the low levels of estradiol and high levels of FSH was missing. These findings suggest that both LH and FSH secretions were impaired. In response to synthetic LRF (150 μg, IV) a qualitatively similar but quantitatively greater release for both LH and FSH was observed. It is interpreted that the impaired gonadotropin secretion was not related to a diminished pituitary gonadotrophin responsiveness to LRF or storage, but rather an inability to release due to insufficient endogenous LRF stimulation. These data indicate that a functional derangement in the hypothalamic LRF-releasing mechanism exists. It would seem appropriate to label this group of patients as “hypogonadotropic hypothalamic amenorrhea,” but the site of defects), whether residing at the level of hypothalamic LRF neurons or suprahypothalamic regulation, remains obscure.