Role of Insulin Resistance in Anovulation

(1)肥胖与无排卵之间的相关性已被广泛认识。最近有报道指出胰岛素抵抗增加与多囊卵巢综合征有关。为探讨胰岛素分泌增加在无排卵中的作用，对克罗米芬抵抗的无排卵患者进行了激素分析和胰岛素分泌的研究。受试者为32例克罗米芬抵抗的无排卵患者。(19例BMI中肥胖大于24的患者为无排卵性肥胖组，13例正常体重的患者为无排卵性正常体重组。)4例排卵周期正常的单纯性肥胖妇女作为对照：排卵性肥胖组。进行激素分析(促黄体生成素、卵泡刺激素、催乳素、雄激素、雌激素)。结果：无排卵性肥胖组和无排卵性正常体重组均存在高雄激素血症和高E_1/E_2比值。无排卵正常体重组促黄体生成素水平和…水平较高黄体生成素/卵泡刺激素比值明显高于无排卵性肥胖组。在无排卵性肥胖组中，75gOGTT的平均基础胰岛素水平和胰岛素反应显著高于对照组。虽然无排卵性正常体重组存在胰岛素抵抗，但无排卵性肥胖组存在严重的胰岛素抵抗。讨论：胰岛素抵抗后胰岛素分泌增加可能是肥胖女性无排卵的直接原因之一。一些报告表明，胰岛素增加了正常女性卵巢雄激素的产生，并增加了培养的人卵泡膜细胞的雄激素产生。高的黄体生成素/卵泡刺激素比率可能是一些多囊卵巢综合征患者恶性循环的另一个直接原因。多囊卵巢综合征可分为胰岛素抵抗显性组和高促黄体生成素/卵泡刺激素比值显性组。(2)近年来有报道指出，无排卵性肥胖妇女体重减轻可提高排卵率。为探讨胰岛素分泌增加在胰岛素抵抗无排卵中的作用，探讨饮食治疗肥胖症无排卵的临床效果。对象：7例BMI中肥胖>24的无排卵患者，4例排卵周期正常的单纯性肥胖妇女作为对照。方法：对饮食治疗前后的患者进行激素分析。建议饮食治疗1600kcal/d，直至BMI减重>5。结果：7例患者中有6例有高水平的黄体生成素和高的黄体生成素/卵泡刺激素比值。所有患者均有高雄激素血症和高E_1/E_2比值。3例患者在75g口服葡萄糖耐量试验期间血糖正常，其余患者表现为潜在的糖尿病模式。无排卵患者平均基础胰岛素水平显著高于对照组。无排卵患者口服75g OGTT后，其循环胰岛素水平的平均升高幅度大于对照组。5例患者体重下降5个以上，其中3例获得性自发排卵周期，2例应用克罗米芬排卵周期。饮食治疗后，高雄激素血症、高E_1/E_2比值和胰岛素分泌增加基本恢复到正常范围。讨论：在肥胖的无排卵女性中，胰岛素抵抗和肥胖之间可能会建立恶性循环。饮食疗法可以打破恶性循环，有利于改善排卵。较少

(1) The correlation between obesity and anovulation has been widely recognized. Recently some reports indicated the association between increased insulin resistance and polycystic ovary syndrome. To investigate the role of increased insulin secretion in anovulation, hormone analysis and insulin secretion in anovulation with clomiphene resistance was studied. Subjects were 32 anovulatory patients with clomiphene resistance. (19 patients had obesity greater than 24 in BMI : anovulatory obese group, and 13 had normal body weight : anovulatory normal weight group.) As a control, 4 simple obese women with normal ovulation cycles : ovulatory obese group. Hormonal analysis (LH,FSH,PRL,Androgens, Estrogens) was performed. Blood glucose concentrations and immuno-reactive insulin levels were measured in 75g OGTT.Results : Anovulatory obese group and anovulatory normal weight group had hyperandrogenism and high E1/E2 ratio similarly. Anovulatory normal weight group indicated higher LH levels and … More higher LH/FSH ratio than anovulatory obese group significantly. In anovulatory obese group, the mean basal level and response of insulin in 75g OGTT were significantly higher than those of control group. Though anovulatory normal weight group showed insulin resistance, anovulatory obese group showed significantly severe insulin resistance. Discussion : Increased insulin secretion following insulin resistance could be one of the direct cause of anovulation in obese women. Some reports indicated that insulin augments ovarian androgen production in normal women and androgen production in cultured human thecal cells. High LH/FSH ratio may be another direct cause of the vicious cycle in some PCOS patients. Polycystic ovary syndrome may consist of insulin resistance dominant group and high LH/FSH dominant group.(2) Recently some reports indicated weight loss in anovulatory obese women results in improvement in ovulation rate. To investigate the role of increased insulin secretion in anovulation with insulin resistance, clinical effect of diet therapy for anovulation with obesity was studied. Subjects : 7 anovulatory patients with obesity greater than 24 in BMI.As a control, 4 simple obese women with normal ovulation cycles. Methods : Hormonal analysis was performed before and after the diet therapy. The diet therapy of 1600 kcal/day was recommended until patients had weight loss more than 5 in BMI.Results : 6/7 patients had high LH levels and high LH/FSH ratios. All patients had hyperandrogenism and high E1/E2 ratios. Three patients showed normal glucose concentrations during 75g OGTT and the others showed latent diabetic patterns. In anovulatory patients, the mean basal insulin level was significantly higher than that in control group. In response to 75g OGTT,the mean rise of circulating insulin level was greater in anovulatory patients than in control group. Five patients could have weight loss more than 5. Three of 5 acquired spontaneous ovulatory cycles, and 2 got ovulatory cycles by clomiphene citrate. Hyperandrogenism, high E1/E2 ratio and increased insulin secretion returned to almost normal range after the diet therapy. Discussion : In anovulatory women with obesity, vicious cycle between insulin resistance and obesity could be established. The diet therapy could destroy the vicious cycle, and be useful for improvement of ovulation. Less