Warren M P, Voussoughian F, Geer E B, Hyle E P, Adberg C L, Ramos R H
Department of Obstetrics and Gynecology, Columbia College of Physicians and Surgeons, New York, New York 10032, USA.
J Clin Endocrinol Metab. 1999 Mar;84(3):873-7. doi: 10.1210/jcem.84.3.5551.
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.
由于功能性或特发性下丘脑性闭经（FHA）的确切病因仍不清楚，FHA仍然是一种排除性诊断。这种疾病可能是由压力诱发的。然而，越来越多的证据表明，代谢/营养损伤可能是主要的致病因素。我们探究了FHA患者甲状腺、激素、饮食、行为和瘦素的变化，因为这些变化为该疾病的病因提供了线索。14名月经周期正常的对照者和闭经的非运动员受试者在年龄、体重和身高方面进行了匹配。闭经受试者否认有饮食失调；只有在进一步详细询问后，我们才发现该组中厌食症和贪食症的发病率较高。闭经受试者出现异常饮食的得分是正常受试者的两倍（P < 0.05），尤其是贪食型行为（P < 0.01）。她们每天在有氧运动中消耗的卡路里也更多，膳食纤维摄入量更高（P < 0.05）；体脂百分比更低（P < 0.05）；游离T4（P < 0.05）、游离T3（P < 0.05）和总T4水平降低（P < 0.05），而反T3或促甲状腺激素无显著变化。闭经者的皮质醇平均水平较高，但无显著差异，而瘦素值显著较低（P < 0.05）。腕部骨密度显著降低（P < 0.05），脊柱骨密度有降低趋势（P < 0.08）。两组之间的情绪困扰和抑郁得分没有差异。FHA患者饮食模式、瘦素水平和甲状腺功能的改变表明营养状况改变，下丘脑 - 垂体 - 甲状腺轴受到抑制，或FHA女性的反馈设定点发生改变。较低的瘦素和甲状腺水平与热量限制时的变化相似。营养问题，特别是功能失调的饮食模式、甲状腺代谢变化和/或瘦素作用，也可能在抑制促性腺激素释放激素分泌的代谢信号和尽管体重正常但骨质减少的发病机制中起作用。这些发现表明，这些女性闭经和低瘦素的机制主要源于代谢/营养损伤。
