Functional hypothalamic amenorrhea: Hypoleptinemia and disordered eating

Because the exact etiology of functional, or idiopathic, hypothalamic ameno rrhea (FHA) is still unknown, FHA remains a diagnosis of exclusion. The dis order may be stress induced. However, mounting evidence points to a metabol ic/nutritional insult that may be the primary causal factor. We explored the thyroid, hormonal, dietary, behavior, and leptin changes th at occur in FHA, as they provide a clue to the etiology of this disorder. F ourteen cycling control and amenorrheic nonathletic subjects were matched f or age, weight, and height. The amenorrheic subjects denied eating disorder s; only after further, detailed questioning did we uncover a higher inciden ce of anorexia and bulimia in this group. The amenorrheic subjects demonstr ated scores of abnormal eating twice those found in normal subjects (P < 0. 05), particularly bulimic type behavior (P < 0.01). They also expended more calories in aerobic activity per day and had higher fiber intakes (P < 0.0 5); lower body fat percentage (P < 0.05); and reduced levels of free T-4 (P < 0.05), free T-3 (P < 0.05), and total T-4 (P < 0.05), without a signific ant change in rT(3) or TSH. Cortisol averaged higher in the amenorrheics, b ut not significantly, whereas leptin values were significantly lower (P < 0 .05). Bone mineral density was significantly lower in the wrist (P < 0.05), with a trend to lower BMD in the spine (P < 0.08). Scores of emotional dis tress and depression did not differ between groups. The alterations in eating patterns, leptin levels, and thyroid function pre sent in subjects with FHA suggest altered nutritional status and the suppre ssion of the hypothalamic-pituitary-thyroid axis or the alteration of feedb ack set-points in women with FHA. Both lower leptin and thyroid levels para llel changes seen with caloric restriction. Nutritional issues, particularl y dysfunctional eating patterns and changes in thyroid metabolism, and/or l eptin effects may also have a role in the metabolic signals suppressing GnR H secretion and the pathogenesis of osteopenia despite normal body weight. These findings suggest that the mechanism of amenorrhea and low leptin in t hese women results mainly from a metabolic/nutritional insult.