Role of Insulin Resistance in Anovulation

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(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