Functional Hypothalamic Amenorrhea: Hypoleptinemia and Disordered Eating

Department of Obstetrics and Gynecology, Columbia University, New York, New York, United States
Journal of Clinical Endocrinology &amp Metabolism (Impact Factor: 6.21). 03/1999; 84(3):873-7. DOI: 10.1210/jc.84.3.873
Source: PubMed


Because the exact etiology of functional, or idiopathic, hypothalamic amenorrhea (FHA) is still unknown, FHA remains a diagnosis of exclusion. The disorder may be stress induced. However, mounting evidence points to a metabolic/nutritional insult that may be the primary causal factor. We explored the thyroid, hormonal, dietary, behavior, and leptin changes that occur in FHA, as they provide a clue to the etiology of this disorder. Fourteen cycling control and amenorrheic nonathletic subjects were matched for age, weight, and height. The amenorrheic subjects denied eating disorders; only after further, detailed questioning did we uncover a higher incidence of anorexia and bulimia in this group. The amenorrheic subjects demonstrated 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 < 0.05); lower body fat percentage (P < 0.05); and reduced levels of free T4 (P < 0.05), free T3 (P < 0.05), and total T4 (P < 0.05), without a significant change in rT3 or TSH. Cortisol averaged higher in the amenorrheics, but 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 distress and depression did not differ between groups. The alterations in eating patterns, leptin levels, and thyroid function present in subjects with FHA suggest altered nutritional status and the suppression of the hypothalamic-pituitary-thyroid axis or the alteration of feedback set-points in women with FHA. Both lower leptin and thyroid levels parallel changes seen with caloric restriction. Nutritional issues, particularly dysfunctional eating patterns and changes in thyroid metabolism, and/or leptin effects may also have a role in the metabolic signals suppressing GnRH secretion and the pathogenesis of osteopenia despite normal body weight. These findings suggest that the mechanism of amenorrhea and low leptin in these women results mainly from a metabolic/nutritional insult.

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    • "Women with functional hypothalamic amenorrhea (FHA), including those with normal BMI, have lower leptin levels than controls, apparently resulting from conditions such as energy balance affecting the leptin/BMI ratio (Andrico et al., 2002). Although a link between leptin concentrations and exercise associated with FHA is suggested by observations that exercising women with FHA have lower leptin levels than ovulating women (Miller et al., 1998; Warren et al., 1999; Corr et al., 2011), when the results are controlled for body fat there is no difference (Corr et al., 2011). Thus, factors other than exercise may also be important in modulation of leptin levels (Tataranni et al., 1997; Laughlin et al., 1998). "
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    • "Hypogonadism is not uncommon in both male and female patients with IBD, and may be the result of (a) a direct effect of inflammation/cytokines on the reproductive axis, ovarian and testicular function [62-64], (b) undernutrition and reduced leptin levels [65] and (c) the effect of chronic GC treatment on gonadotrophin secretion [33] (as already discussed in the paragraph discussing treatment of osteoporosis). "
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    • "When prepubertal animals, including primates, are exposed to energy deprivation the onset of puberty is delayed or even blocked, until a favorable energy balance is achieved (Kennedy and Mitra, 1963; Kennedy, 1969; Foster and Olster, 1985). In adults, severe energy deficits are a frequent cause of hypothalamic amenorrhea (Warren et al., 1999; Welt et al., 2004; Ribeiro et al., 2007). Recent studies not only confirm the importance of the adiposity in influencing the onset of puberty, but also suggest that excess of body fat in children cause early onset of puberty (Biro et al., 2010). "
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