Hypothyroidism and amenorrhea due to hypothalamic insufficiency. A study in four young women

Four women, aged 17 to 23, were evaluated for secondary amenorrhea of 12 to 36 months' duration. All were considered to have hypothalamic hypothyroidism on the basis of low thyroxine (T4) concentrations, inappropriately low thyrotropin (TSH) levels, with a normal TSH response to thyrotropin-releasing hormone (TRH, 500 microgram intravenously) in three, and absence of a pituitary lesion. Nevertheless, menses did not resume after adequate replacement with thyroid hormone. Investigation of the pituitary-gonadal axis revealed a normal increase in both luteinizing hormone (LH) and follicle-stimulating hormone (FSH) following the intravenous administration of gonadotropin-releasing hormone (GnRH). Three subjects received clomiphene citrate, 100 mg/day for five days, but a normal menstrual cycle was not induced. It is concluded that the amenorrhea was not due to thyroid hormone deficiency but, like the hypothyroidism, to a hypothalamic abnormality involving secretion of the appropriate releasing hormone.