Nutritional and endocrine-metabolic aberrations in women with functional hypothalamic amenorrhea
Nutritional and endocrine-metabolic aberrations in women with functional hypothalamic amenorrhea
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DOI：
10.1210/jc.83.1.25
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发表时间：
1998-01-01
影响因子：
5.8
通讯作者：
Yen, SSC
中科院分区：
文献类型：
--
作者：
Laughlin, GA;Dominguez, CE;Yen, SSC
长期以来，体重稳定、不运动的女性发生功能性下丘脑性闭经被认为是心因性的。本研究旨在深入了解营养缺乏和代偿性内分泌代谢适应有助于心因性FHA的发展和维持的可能性。在8名与运动或体重减轻无关的FHA女性和8名年龄和体重指数匹配的定期骑自行车对照（NC）中，同时评估了营养摄入、胰岛素敏感性和胰岛素/葡萄糖、皮质醇、瘦素、促生长激素和LH轴的24小时动态。FHA组的脂肪体质量百分比低于NC组，而瘦体质量高于NC组（P < 0.05）。FHA受试者在两个进食障碍量表子量表上的得分高于NC（P < 0.05），Beck抑郁评分高于NC（P（0.05）），尽管都在亚临床范围内。虽然每天的热量摄入量没有差异，但FHA消耗的热量少了50（P < 0.001）脂肪组，两次（P < 0.05）高纤维、高碳水化合物在一天的进食阶段，FHA显示出较低的葡萄糖低胰岛素血症的程度与膳食脂肪含量呈正相关（r = 0.73）。虽然24小时的平均GH水平没有差异，GH释放的模式在FHA明显改变，从NC。与NC相比，FHA组GH脉冲幅度变钝，脉冲频率加快40%（P < 0.01），脉冲间GH浓度全天升高2倍（P < 0.01）。这种扭曲的GH脉冲模式与GH结合蛋白水平下降40%（P < 0.01）有关。胰岛素依赖性胰岛素样生长因子（IGF）结合蛋白-1（IGFBP-1）的水平在FHA组和NC组中在一天的进食部分期间升高（P < 0.001），并且与胰岛素呈负相关（r = -0.50），与皮质醇水平呈正相关（r = 0.64）。虽然IGF-I和IGFBP-3水平无差异，但FHA中IGFBP-1水平升高导致IGF-I/IGFBP-1比值降低（P < 0.01），这可能会降低IGF-I的生物活性和降血糖作用。FHA组24小时平均瘦素水平和瘦素昼夜波动与NC组无差异。FHA组LH脉冲频率减慢50%（P < 0.001），脉冲幅度不变，导致FHA组24小时平均LH水平比NC组低45%（P < 0.01）。两组LH脉冲频率与胰岛素呈正相关（r = 0.80）水平和IGF-I/IGFBP-1比值与皮质醇呈负相关（r = 0.70）（r = -0.61）和IGFBP-1（r = -0.72）浓度。总之，我们发现体重稳定，患有FHA的非运动型女性，伴有严格限制膳食脂肪摄入。心因性FHA患者营养摄入不平衡与多种内分泌代谢改变相关。其中，血浆葡萄糖和血清GHBP水平降低、IGF-I/IGFBP-1比值降低、GH脉冲频率加快和脉冲间GH水平升高表明代谢低下状态。此外，葡萄糖调节反应的幅度（皮质醇分泌增加和胰岛素/IGF-I作用降低）与GnRH/LH脉冲频率的抑制程度直接相关。这些结果与接受过FHA训练的运动员非常相似（1）。因此，营养缺乏可能是导致心因性和运动相关FHA的多种神经内分泌代谢异常发生和维持的共同因素。
The development of functional hypothalamic amenorrhea (FHA) in weight-stable, nonathletic women has long been thought to be psychogenic in origin. This study was designed to gain insight into the possibility that nutritional deficits and compensatory endocrine-metabolic adaptations contribute to the development and maintenance of FHA of the psychogenic type. Nutritional intake, insulin sensitivity, and 24-h dynamics of insulin/glucose, cortisol, leptin, somatotropic, and LH axes were simultaneously assessed in eight women with FHA not associated with exercise or weight loss and in eight age-and body mass index-matched regular cycling controls (NC). The percent fat body mass was lower and lean body mass was higher in FHA than in NC (P < 0.05). The FHA subjects scored higher (P < 0.05) on two Eating Disorder Inventory subscales and had a higher (P ( 0.05) Beck depression rating than NC, although all were in the subclinical range. Although daily caloric intake did not differ, FHA consumed 50% less (P < 0.001) fat, twice (P < 0.05) as much fiber, and more carbohydrate (P < 0.05) compared to NC.During the feeding phase of the day, FHA exhibited lower glucose (P < 0.05) and insulin (P < 0.01) levels than NC, and the degree of hypoinsulinemia was directly related to relative dietary fat (r = 0.73). Although 24-h mean GH levels did not differ, the pattern of GH release in FHA was distinctly altered from that in NC. GH pulse amplitude was blunted, pulse frequency was accelerated 40% (P < 0.01), and interpulse GH concentrations were elevated 2-fold (P < 0.01) throughout the day for FHA compared to NC. This distorted pattern of GH pulses was associated with a 40% decrease (P < 0.01) in GH-binding protein levels. Levels of the insulin-dependent insulinlike growth factor (IGF)-binding protein-1 (IGFBP-1) were elevated (P < 0.001) during the feeding portion of the day in FHA and were inversely related to insulin (r = -0.50) and directly related to cortisol (r = 0.64) levels for FHA and NC groups together. Although levels of IGF-I and IGFBP-3 did not differ, the elevation of IGFBP-1 levels in FHA resulted in a reduced (P < 0.01) ratio of IGF-I/IGFBP-1, which may decrease the bioactivity and hypoglycemic effect of IGF-I. Twenty-four-hour mean leptin levels and the diurnal excursion of leptin in FHA did not differ from those in NC. LH pulse frequency was slowed 50% (P < 0.001) in FHA, with unaltered pulse amplitude, resulting in 45% lower (P < 0.01) 24-h mean LH levels for FHA compared to NC. LH pulse frequency for the two groups was related positively to insulin (r = 0.80) levels and the ratio of IGF-I/IGFBP-1 (r = 0.70) and negatively with cortisol (r = -0.61) and IGFBP-1 (r = -0.72) concentrations.In summary, we found evidence of subclinical eating disorders in weight-stable, nonathletic women with FHA accompanied by a severe restriction of dietary fat intake. Unbalanced nutrient intake in psychogenic FHA was associated with multiple endocrine-metabolic alterations. Among these, reduced levels of plasma glucose and serum GHBP, a decrease in the ratio of IGF-I/IGFBP-1, accelerated GH pulse frequency, and elevated interpulse GH levels are indicative of a hypometabolic state. In addition, the magnitude of glucoregulatory responses (increased cortisol secretion and decreased insulin/IGF-I action) were directly related to the degree of suppression of GnRH/LH pulse frequency. These results are remarkably similar to those seen in highly trained athletes with FHA(1). Thus, nutritional deficits may represent a common contributing factor to the development and maintenance of multiple neuroendocrine-metabolic aberrations underlying both psychogenic and exercise-related FHA.