Functional Hypothalamic Amenorrhea is Associated With Elevated Ghrelin and Disordered Eating

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Functional hypothalamic amenorrhea (FHA) relates to a set of neuroendocrine abnormalities that suggest centrally dysregulated reproductive function. Affected women also exhibit disordered eating. Conceivably a restraining metabolic signal indicating inadequate nutritional status and abnormal eating behavior is present in women with FHA. This signal could suppress the normal pulsatility of gonadotropin-releasing hormone secretion and thereby prevent normal menstruation. Both leptin and ghrelin are linked with eating behavior and are plausible candidates to be the metabolic signal. This controlled clinical study was planned to learn whether ghrelin, an orexigen released by the stomach, is elevated in women with FHA and normal body weight. Levels of both ghrelin and leptin were estimated in 27 women diagnosed as having FHA and 42 women with normal menses. Eating disorders were assessed by interviews and questionnaires including the Eating Attitudes Test (EAT). The FHA and control groups were similar in age and height, but women with FHA had significantly lower body weight, body mass indices, and percent body fat. They also exercised more than control women, although not significantly so. Anorexia was identified in 15% of both groups. Bulimia was more frequent in the FHA group, but again not significantly. Overall EAT scores and bulimia subscale scores were significantly higher for the FHA patients, who consumed significantly more kilocalories than did control women and also ate more carbohydrates. Gonadotropin levels were similar in the two groups but estradiol levels were lower in FHA patients. Leptin levels also were lower, but not significantly. Levels of ghrelin were significantly elevated in the FHA group (648 versus 597 pg/mL on average). Neither exercise status nor body mass index could be related to ghrelin levels. These findings suggest that elevated blood ghrelin levels may signify a drive to eat in women who customarily limit their food intake. High levels may help to explain why amenorrhea continues after a return to normal body weight. Estimating levels of ghrelin may point to those patients who could benefit from nutritional counseling.