Functional Hypothalamic Amenorrhoea: A Partial and Reversible Gonadotropin Deficiency of Nutritional Origin

Abstract

Both inadequate nutrition (as in anorexia nervosa) and intensive exercise contribute to functional hypothalamic amenorrhea (FHA). In this study, the role of impaired gonadotropin-releasing hormone (GnRH) secretion in FHA, its possible nutritional origin, and its reversibility were studied. Twelve women aged 22 to 35 years with FHA not related to exercise were compared with 12 regular-cycling control women matched for age and body size and with six women with congenital hypothalamic hypogonadism (CHH), three of whom had Kallmann’s syndrome. None of the women had primary amenorrhea, and all had normal magnetic resonance images of the hypothalamic-pituitary region. Transvaginal ultrasonography demonstrated small, multifollicular ovaries. The women with FHA were studied 10 days after a negative result was obtained on a progesterone test, and those with CHH were studied 2 months after withdrawal of hormone therapy. Normal women were evaluated during the early follicular phase of the cycle. Nutritional status was assessed by obtaining a detailed dietary history and measurements of body weight and body mass index. The women with FHA were advised to consume an 1800-calorie diet with 30 percent fat, 20 percent protein, and 50 percent carbohydrate, but only three of them were able to do so. Women with FHA had lower plasma levels of estradiol and androstenedione than healthy women but higher levels than women with CHH. Plasma dehydroepiandrosterone sulfate levels were higher in women with FHA than in healthy control subjects. LH secretion was suppressed in all respects in women with FHA; those with CHH had no LH pulses. In contrast to what occurred in women with CHH, in women with FHA, the FSH/LH ratio increased rapidly after injection of the GnRH agonist triptorelin, and the plasma estradiol response was similar to that in healthy control subjects. The three patients with FHA who increased their caloric intake had spontaneous uterine bleeding and regained normal pulsatile LH secretion. Compared with normal women, those with FHA had less body fat and a higher lean body mass. They consumed significantly less dietary fat and carbohydrate than control subjects matched for body mass index. The FHA group had increased plasma levels of sex hormone–binding globulin and significantly decreased levels of several nutritional markers, including ferritin, leptin, and insulin-like growth factor 1. Nutritional disorder is a prominent abnormality in most women with FHA. To maintain a low body weight, they adopt deviate attitudes toward food, selecting few fat calories and sometimes increasing their activity level. Impaired GnRH secretion is part of the picture but is partial and can be reversed by consuming a proper diet for several months. Clin Endocrinol (Oxf) 1999;50:229–235