Prevalencia del síndrome del ovario poliquístico y de factores de riesgo cardiovascular en mujeres obesas premenopáusicas

Resumen

Background: The polycystic ovary syndrome (PCOS) is probably the most common endocrine disorder in premenopausal women, presenting with an overall prevalence of 6.5 % in the Spanish population. PCOS is frequently associated with an impairment of quality of life and several cardiovascular risk factors, such as an increased risk of type 2 diabetes, dyslypidemia, and obesity, which is presented in more than half of women with this condition. Although the primary defect of PCOS appears to consist of an increased androgen synthesis and secretion by ovarian theca cells, obesity and the hyperinsulinism that results from insulin resistance may play an important role in the pathogenesis of PCOS. Surprisingly, the actual prevalence of PCOS in otherwise unselected overweight and obese women remains unknown. Objectives: 1) To estimate the prevalence of the polycystic ovary syndrome, of the metabolic syndrome and of other conditions related to cardiovascular risk, in unselected premenopausal women with overweight or obesity. 2) To determine the differences in factors related to the etiopathogenesis of obesity, among overweight or obese women presenting with or without the polycystic ovary syndrome. 3) To confirm the influence of the grade of obesity in the development of the polycystic ovary syndrome and of the metabolic disorders commonly associated with this syndrome. Material and methods: All the premenopausal women referred by their general physicians to the Department of Endocrinology of Hospital Universitario Ramón y Cajal for weight loss were prospectively evaluated. Women referred for any other reason, and those taking medications that might interfere with hormone profiles, were automatically excluded to avoid selection bias. The diagnosis of PCOS was made according to NICHD criteria. Patients and controls were submitted to a complete evaluation that included anthropometric, laboratory and hormonal measurements. Insulin sensitivity was estimated by the composite insulin sensitivity index (ISI) derived from the glucose and insulin concentrations during a 75gr glucose oral tolerance test. The diagnosis of metabolic syndrome was established according to the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Diet composition was estimated by a modification of the semi-quatitative Harvard Service Food Frequency Questionnaire that has been validated in the Spanish population. Quality of life was evaluated by the SF-36 questionnaire and the Nottingham Health Profile questionnaire. Data are expressed as means SD. Logarithmic or square root transformation were applied to ensure normality as needed, and variables showing a normal distribution were submitted to a general linear model introducing the presence or absence of PCOS as independent variable, and age as a covariate to correct for a difference in this variable among patients and controls. The comparison of variables that remained skewed was analyzed by the Mann-Whitney U test. Discontinuous variables were analyzed by Pearson χ2 or Fisher exact test. P < 0.05 was considered statistically significant. Results: Of a total of 113 consecutive women evaluated, 32 were diagnosed with PCOS for a 28% prevalence of this syndrome in overweight or obese women (95% confidence interval: 20% - 37% ). However, the prevalence of PCOS was not statistically different when considering the grade of obesity. The prevalence of the metabolic syndrome, hypertension, dyslipidemia and of abnormalities of glucose tolerance were similar in PCOS or control group, yet when considering the influence of the grade of obesity on the development of these conditions, we observed an increase of the prevalence in the subgroups with higher grades of obesity compared with the subgroup of overweight women. With regards to diet composition, we did not observe any difference in the intake of either daily energy intake or of macro- or micronutrients, whereas the control group presented with a higher consumption of caffeine compared with PCOS women. Quality of life was similar in both groups of patients, except for the emotional role, which was impaired in PCOS women. However, when considering the effect of the grade of obesity in quality of life, we observed poorer scores in several domains of quality of life in the groups with higher body mass index. Finally, C-reactive protein and haptoglobin, considered as serum markers of chronic inflammation, were similar in PCOS and control group, but notably elevated in patients with a higher grades of obesity. On the contrary, serum ferritin concentration was elevated in PCOS patients, probably because of the compensatory hyperinsulinism related to insulin resistance in these women. Conclusion: To our best knowledge, our present study is the first addressing the prevalence of PCOS in unselected premenopausal overweight or obese women seeking advice for weight loss, showing a 5-fold increase with respect to the prevalence in lean women from the general population living in the same city (28% vs 6%, respectively). The increased prevalence of PCOS was found in overweight and obese women, irrespective of the grade of obesity and independently from the presence or absence of the metabolic syndrome, suggesting that obesity and insulin resistance may be important contributors to the development of PCOS, but are not the major etiologic defects leading to this disorder. In contrast, the metabolic syndrome and classic cardiovascular risk factors were much more dependent on the grade of obesity, with an increase of their prevalence in women presenting with grade 2 or grade 3 obesity further suggesting that insulin resistance played an essential role in their development. To this regards, differences of dietary intake did not appear to be involved in the insulin resistant state characteristic of PCOS patients. Obesity, but not PCOS, was related with the poorer quality of life observed in the women evaluated, yet PCOS women show an impairment in the emotional role scores that was independent of obesity. Finally, serum markers of chronic inflammation were mainly dependent on the grade of obesity, except for a higher serum ferritin levels in PCOS women. We may conclude that physicians treating overweight and obese patients should be aware of the high prevalence of PCOS among these women, and that screening for PCOS, at least by obtaining a detailed menstrual history and a careful clinical evaluation of hyperandrogenic symptoms, should be conducted routinely in order to diagnose PCOS and ameliorate the health burden distinctly associated with this prevalent disorder.