MECHANISMS IN ENDOCRINOLOGY: Recent advances in cardiovascular aspects of polycystic ovary syndrome

Abstract

Polycystic ovary syndrome (PCOS) has been associated with increased cardiovascular risk (CVR) markers, but population studies have not clarified whether there is an increase in cardiovascular morbidity and mortality. Four different PCOS phenotypes resulted from the Rotterdam criteria that may differ in their CVR potential, thus introducing further complexity. This has led to studies using surrogate CVR markers including biomarkers in blood and imaging such as flow-mediated vasodilatation. In PCOS, both peripheral and central insulin resistance (IR) have been shown. Weight loss has been shown to improve IR and visceral fat, while insulin sensitizer therapies with metformin or thiazolidinediones improve IR and endothelial dysfunction. IR is also found in non-alcoholic fatty liver disease that in turn is very common in PCOS; studies have suggested that IR may be improved by treatment with metformin and omega-3 fish oils. PCOS patients have a more dyslipidemic phenotype that is worse in 'classical PCOS' associated with a higher CVR. Studies with atorvastatin and simvastatin have reported a decrease in the lipid parameters and an improvement in CVR indices including IR, but it is unclear whether this is due to their lipid-lowering action or a pleiotropic effect of the statin. In this expert opinion review, the relevant literature published during the last 2 years was considered. It focuses on some recent important data that has emerged while also exposing the gaps that remain in our knowledge that need to be addressed.

Cardiovascular disease in transsexual persons treated with cross-sex hormones: reversal of the traditional sex difference in cardiovascular disease pattern

“…Diabetes was often encountered in the study population of MtoF and FtoM in the study of Wierckx et al (27). 5) It is remarkable that women with hyperandrogenism have a high number of surrogate cardiovascular risk factors, but there is limited convincing evidence that high endogenous or exogenous androgens increase cardiovascular pathology (60). In FtoM, testosterone administration does not induce hyperinsulinism (54).…”

“…Hyperandrogenic women with the polycystic ovarian syndrome have an established increased risk of developing type 2 diabetes (57) and many cardiovascular risks (58) but a still debated increased risk of cardiovascular disease (59). It is still not clear why, in view of the many cardiovascular risk factors, there is no overwhelming increase in cardiovascular morbidity and mortality in women with the polycystic ovarian syndrome (60). In a study comparing testosterone-treated FtoM with hyperandrogenic women with polycystic ovarian syndrome, we found that testosterone administration induced a decline in serum HDL and increase in triglycerides, but had no effect on insulin resistance, a frequent feature of PCOS (54).…”

European survey of diagnosis and management of the polycystic ovary syndrome: results of the ESE PCOS Special Interest Group's Questionnaire

“…On the other hand, androgen excess per se and related metabolic issues are typical areas of endocrinological interest, and the current survey by ESE clearly expresses the considerable interest of endocrinologists in Europe in the field. There are some differences between endocrinologists and gynecologists in the definition, diagnosis, and treatment of PCOS, as documented by a recent survey performed in Australia (9) and as shown by many review articles written by gynecologists or endocrinologists (11,12,13). Whereas the latter regarded androgen excess and menstrual irregularity as the major diagnostic criteria, the former were more likely to list ovarian morphology and menstrual irregularities as the main criteria, with androgenization further down the list.…”

Cardiometabolic and reproductive benefits of early dietary energy restriction and voluntary exercise in an obese PCOS-prone rodent model

“…Furthermore, in prepubertal or adolescents predisposed to the development of PCOS associated with obesity, early intervention to address dietary energy intake and exercise habits may prevent the development and onset of PCOS in these individuals. This in turn may prevent long-term cardiometabolic risk and adverse reproductive and fertility outcomes associated with PCOS (Alexander et al 2009, Sathyapalan & Atkin 2012.…”

“…The manifestation of PCOS in overweight-obese adolescents is likely to originate in prepuberty (Diamanti-Kandarakis et al 2007), predisposing individuals to increased cardiometabolic risk, including dyslipidemia and impaired glucose tolerance, leading to early development of type II diabetes and cardiovascular disease (Alexander et al 2009, Fulghesu et al 2010, Sathyapalan & Atkin 2012, Dantas et al 2013. Insulin resistance (IR) is strongly implicated in the etiology of PCOS (Baillargeon & Nestler 2006, Diamanti-Kandarakis & Dunaif 2012 and hyperinsulinemia has been shown to stimulate androgen production in ovarian thecal cells and to reduce hepatic sex-hormone binding globulin (SHBG) synthesis (Barbieri et al 1984, Nestler et al 1991.…”