Insulin resistance causes impaired vasodilation and hypofibrinolysis in young women with polycystic ovary syndrome.

INTRODUCTION: Insulin resistance, a novel cardiovascular risk factor, is often associated with increased plasminogen activator inhibitor-1 levels and impaired vasodilation. Insulin infusion in the forearm induces plasminogen activator inhibitor-1 and tissue plasminogen activator expression and endothelium-dependent vasodilation in normal subjects. The present study explores the relationship between insulin-induced vasodilatory and fibrinolytic properties of the endothelium in women with polycystic ovary syndrome, frequently affected by insulin resistance and early atherosclerosis. MATERIALS AND METHODS: Metabolic, hormonal and fibrinolytic parameters were evaluated in 64 patients with polycystic ovary syndrome (19 insulin-resistant and 45 insulin-sensitive) and in 25 controls. In 16 women with polycystic ovary syndrome, 8 insulin-resistant and 8 insulin-sensitive, blood flow, plasminogen activator inhibitor-1 and tissue plasminogen activator expression were evaluated during insulin infusion into the forearm. RESULTS: Elevated basal plasminogen activator inhibitor-1 levels were found in women with polycystic ovary syndrome, correlating directly with insulin levels. Plasminogen activator inhibitor-1 expression increased during insulin infusion in all women with polycystic ovary syndrome, but was delayed and sustained in insulin-resistant patients (p<0.01). Vasodilatory response to insulin was blunted (p<0.01) and tissue plasminogen activator expression abolished in insulin-resistant patients (p<0.01). CONCLUSION: Our study demonstrates that women with polycystic ovary syndrome and insulin resistance show a blunted endothelial-dependent vasodilation. The impaired endothelial release of tissue-plasminogen activator and the sustained plasminogen activator inhibitor-1 release during insulin infusion suggest a hypofibrinolytic state in PCOS patients with insulin resistance. This hemodynamic and fibrinolytic derangement may contribute to the pathogenesis of early atherosclerosis in insulin resistance.

Effect of long-term naltrexone treatment on endocrine profile, clinical features, and insulin sensitivity in obese women with polycystic ovary syndrome.

OBJECTIVE: Evaluation of clinical and endocrine effects of naltrexone administration in obese women with PCOS. DESIGN: Open, controlled, clinical study. SETTING: Department of Reproductive Medicine and Child Development, Section of Gynecology and Obstetrics, University of Pisa, Pisa, Italy. PATIENT(S): Ten PCOS women were studied. INTERVENTION(S): Women were treated with naltrexone (50 mg/day) for 6 months. MAIN OUTCOME MEASURE(S): Body mass index and the menstrual cyclicity during naltrexone treatment were assessed. Basal levels of LH, FSH, 17beta-estradiol (E(2)), 17-hydroxyprogesterone, total and free T, androstenedione, dehydroepiandrosterone sulfate, cortisol, sex hormone-binding globulin were evaluated before treatment and every 3 months. Progesterone levels were measured in the luteal phase during the sixth month. Gonadotropin response to GnRH administration (10 microg) and a 75-g oral glucose tolerance test were performed before and every 3 months. RESULT(S): Body mass index significantly decreased from 29.94 +/- 1.04 to 26.07 +/- 0.81 during treatment. The menstrual cyclicity improved in 80% of PCOS women: the mean cycle length was 40-360 days before treatment and ranged between 25 and 120 days and 28-120 days after 3 and 6 months of treatment. Plasma levels of free T, androstenedione, dehydroepiandrosterone sulfate, and cortisol significantly decreased. Fasting glucose-to-insulin ratio improved in women with insulin resistance. CONCLUSION(S): Naltrexone may have a beneficial effect on the clinical and endocrine-metabolic disturbances of obese PCOS women. Whether these effects are the consequences of weight loss or are due to changes in opioidergic tone is debatable.