Long-term reproductive and metabolic consequences of PCOS.

Polycystic ovary syndrome (PCOS) is associated with reproductive and metabolic consequences. The review of findings indicate that the long-term reproductive outcomes of women with PCOS are surprisingly similar compared to women with normal ovaries, and that they have an ovarian reserve possibly superior to women with normal ovaries. The typical features of PCOS, specifically the anovulatory cycles tend to normalize over time, but in spite of a decrease over time, free androgen levels remain elevated compared to age-matched control subjects. Women with PCOS diagnosed at young age continue to display reduced insulin sensitivity in the perimenopausal age, independent from phenotypic expression of PCOS, both at diagnosis and at follow-up. Insulin resistance does not seem to deteriorate further, however. Overall, the accumulated data from several European cohort studies of older women with a previous diagnosis of PCOS suggest an increased incidence of type 2 diabetes, increased prevalence of several features of the metabolic syndrome, but no increased incidence of mortality from CVD.

Prevalence of the metabolic syndrome in women with a previous diagnosis of polycystic ovary syndrome: long-term follow-up.

OBJECTIVE: To examine the prevalence of the metabolic syndrome (MetS) according to the scientific statement of the American Heart Association and the US National Cholesterol Education Program/Adult Treatment Panel III in middle-aged Swedish women previously diagnosed with polycystic ovary syndrome (PCOS) in comparison with age-matched healthy controls. DESIGN: Long-term follow-up study. SETTING: Department of Obstetrics and Gynecology, Uppsala University. PATIENT(S): Eighty-four women diagnosed with PCOS between 1987 and 1995; and 87 controls randomly selected from the general population. INTERVENTION(S): Anthropometric measurements and blood tests. MAIN OUTCOME MEASURE(S): Body mass index, waist circumference, blood pressure, lipids, and glucose. RESULT(S): The prevalence of MetS in women with PCOS (mean ± SD age, 43.0 ± 5.8 years) was 23.8% and in controls was 8.0%, and it did not differ according to PCOS phenotype at the index assessment (polycystic ovaries [PCO], oligomenorrhea, and hirsutism: 10 [22.7%]; PCO and oligomenorrhea: 8 [22.2%]) or according to the persistence of PCOS features at follow-up (persisting PCOS: 25.8%; resolved PCOS: 16.7%). CONCLUSION(S): The MetS occurred more often in patients with PCOS than in controls and did not depend on phenotypic presentation at the index assessment or the persistence of PCOS at follow-up.

Androgen levels, insulin sensitivity, and early insulin response in women with polycystic ovary syndrome: a long-term follow-up study.

Thirty-four women with polycystic ovary syndrome who previously had participated in studies with intravenous glucose tolerance test and hyperinsulinemic, euglycemic clamp between 1987 and 1995 underwent anthropometric, endocrine (T and sex-hormone binding globulin serum concentration), and metabolic (intravenous glucose tolerance test, hyperinsulinemic, euglycemic clamp, and androgens) measurements. Free androgen levels and ß-cell function decreased over time in women with polycystic ovary syndrome, but insulin sensitivity remained unaltered.

Patients with polycystic ovary syndrome have lower levels of IgM anti-phosphorylcholine antibodies than healthy women.

INTRODUCTION: IgM antibodies against phosphorylcholine (IgM anti-PC) are natural autoantibodies, possibly exerting one of the atheroprotective functions of the immune system. Increased levels of these antibodies reduce the development of atherosclerosis in mice, and low levels of IgM anti-PC have been associated with increased risk for cardiovascular disease (CVD). This study compared levels of IgM anti-PC in women with polycystic ovary syndrome (PCOS, n = 111) and healthy controls (n = 79). METHOD: Levels of IgM anti-PC were measured with ELISA. RESULTS: The median level of IgM anti-PC in patients with PCOS was not significantly different compared to control subjects. However, the proportion of patients with PCOS with low levels of IgM anti-PC, defined as number of individuals below the median level, was significantly higher than among healthy controls, p < 0.05. Patients with PCOS in the oldest age quintile had significantly lower level of IgM anti-PC than control subjects of similar age (p < 0.05) and younger women with PCOS (p < 0.01). CONCLUSION: Our results indicate that women with PCOS more frequently display below-median levels of IgM anti-PC than controls and older women with PCOS have lower median anti-PC levels. Further studies of how this finding translates into actual CVD risk in women with PCOS are needed.

Tissue plasminogen activator and plasminogen activator inhibitor 1 in obese and lean patients with polycystic ovary syndrome.

OBJECTIVE: Disturbances in the fibrinolytic system are predictors of future cardiovascular events. The aim of this study was to compare plasminogen activator inhibitor 1 (PAI-1) activity and tissue plasminogen activator (tPA) mass concentration between patients with polycystic ovary syndrome (PCOS) and control subjects. DESIGN: One hundred thirty-five patients with PCOS (lean and obese) and 81 healthy controls were recruited for the study. Blood samples for PAI-1 activity and tPA mass were collected together with anthropometric measures. RESULTS: Obese patients with PCOS displayed increased tPA mass concentration in comparison with controls (p <0.05), and this finding was consistent regardless of whether patients displayed signs of hyperandrogenism or not. When hyperandrogenism was introduced as a prerequisite for the PCOS diagnosis, obese patients with PCOS displayed increased PAI-1 activity as well, p <0.05. Lean patients with PCOS did not differ in terms of PAI-1 activity or tPA mass concentration in comparison to controls. CONCLUSION: Obese women with PCOS have impaired fibrinolysis, in particular if they also display objective biochemical markers of hyperandrogenism.

Endothelial function in patients with polycystic ovary syndrome: a long-term follow-up study.

OBJECTIVE: To investigate pulse wave reflection and endothelial-dependent vasodilation in patients with polycystic ovary syndrome (PCOS) and age-matched healthy controls. DESIGN: Long-term follow-up study. SETTING: Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden. PATIENT(S): Sixty-seven patients with PCOS and with a mean age of 43.3 years at the follow-up investigation and 66 age-matched controls. INTERVENTION(S): Aplanation tonometry before and after ß-2 receptor agonist (terbutaline) challenge. MAIN OUTCOME MEASURE(S): Baseline augmentation index (AI) aorta, baseline AI-radial, and change in AI-radial after terbutaline administration as a measure of endothelial-dependent vasodilation. RESULT(S): There was no difference in baseline AI-aorta between patients with PCOS and control subjects. Change in AI-radial after terbutaline administration was less pronounced in patients with PCOS compared with control subjects. This difference remained when adjusted for use of combined oral contraceptives (OC)/hormone replacement therapy (HT) and postmenopausal status but not after adjustment for body mass index (BMI). CONCLUSION(S): Middle-aged patients with PCOS display signs of endothelial dysfunction in comparison to age-matched controls, but this is largely due to the increased prevalence of independent risk factors for cardiovascular disease found in this group.