Primary amenorrhea, in which serum concentrations of gonadotropins are low or normal, has been considered to be relatively rare. Recent analysis in our outpatient clinic revealed that the incidence of hypothalamic primary amenorrhea is higher than previously appreciated, comprising 26.7% of the total primary amenorrheas. Endocrinological functions of the hypothalamo-hypophyseo-ovarian axis in these patients were therefore investigated. Studies on gonadotropin secretion indicated that a disturbance in LH-RH secretion and a lack of estrogen positive feedback were principle features of this disease. In addition to the dysfunction of gonadotropin secretion, the control of PRL secretion was disturbed in this disease since there was a poor PRL response to chlorpromazine in spite of normal responsiveness to TRH. Thus, “isolated gonadotropin deficiency” hitherto used to describe this disease is not pertinent. Furthermore, these results suggest that PRL might be involved in the onset of puberty in humans. Clinically, the induction of ovulation with HMG (Human Menopausal Gonadotropin) is possible in hypothalamic primary amenorrhea, although the ovarian responsiveness to gonadotropin is poor. Therefore, an endocrinologically precise diagnosis of hypothalamic primary amenorrhea is important in the gynecological clinic because fertility has been considered to be almost impossible in primary amenorrhea.
