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The study was supported by a research grant by the Serbian Ministry of Science and Education (grant nos 41009 and 175032). All authors have no competing interests.

Polycystic ovary syndrome (PCOS) is a common metabolic and reproductive disorder in women. An increased cardiovascular risk has to be anticipated in PCOS as it is a metabolically unstable condition. Among cardiovascular risk factors, dyslipidemia is certainly the most persistent and highly prevalent. Predominant observation is an elevation of LDL cholesterol in all PCOS patients. Decreased concentrations of HDL cholesterol are found in obese PCOS from the third decade of life onwards while triglycerides start to rise from the second decade of life. PCOS is associated with oxidative stress, namely increased production of free radicals followed by decreased serum antioxidant levels and antioxidant enzyme activity. Broad range of endocrine and metabolic disturbances like obesity, hyperinsulinemia as well as dyslipidemia might be responsible for PCOS-associated oxidative stress. Therapeutic interventions in PCOS women based on lifestyle modification as well as use of insulin sensitizers did not show significant effect on dyslipidemia. Statins are considered to be a group of promising agents that are safe and effective in improving total cholesterol, LDL cholesterol and triglycerides, and possess antioxidant activity. Supplementation with omega-3 fatty acids, α-lipoic acid and N-acetylcysteine is considered to have an anti-inflammatory and antioxidant effect and to improve dyslipidemia and insulin sensitivity in PCOS women.

Polycystic ovary syndrome (PCOS) is a frequent endocrine disease in women, with a number of metabolic and reproductive consequences. Obesity, insulin resistance (IR) and type 2 diabetes are prominent metabolic characteristics of PCOS and common factors affecting liver function and generating nonalcoholic fatty liver disease (NAFLD). Multiple genes involved in the synthesis of androgens, cytokines and IR, as well as acquired factors, such as endocrine disruptors, could associate the etiopathogenesis of PCOS and NAFLD. Besides the high prevalence of PCOS in general population, NAFLD was shown to be a frequent condition in transition periods, such as adolescence and menopause. Although liver biopsy is considered to be the gold standard for diagnosing liver damage, its routine use in such a prevalent condition as PCOS can be related to a higher rate of complications. Therefore, it is necessary to be able to diagnose NAFLD using simple and reliable surrogate markers. Recently, fatty liver index and NAFLD fatty liver score analyzed in large cohorts of PCOS women have been shown as accurate markers of liver damage in this metabolically vulnerable population. Lifestyle changes are still the mainstay of the management of NAFLD in PCOS, although prospective randomized controlled clinical studies remain a priority in the field. With regard to medications, metformin may be the drug of choice for treating PCOS patients with NAFLD when pharmacologic therapy is considered. Liraglutide use in obese PCOS has shown favorable effects on the predictors of liver fibrosis. In this review, we aim to summarize the influence of the common risk factors and to discuss the diagnostic approaches and management options for NAFLD in patients with PCOS.

The deficiency of 21-hydroxylase due to CYP21A2 pathogenic variants is a rather frequent disease with serious consequences, going from a real mortality risk to infertility and to milder symptoms, nevertheless important for affecting the patients' self-esteem. In the most severe cases life-threatening adrenal salt wasting crises may occur. Significant morbidity including the possibility of mistaken gender determination, precocious puberty, infertility and growth arrest with consequent short stature may also affect these patients. In the less severe cases milder symptoms like hirsutism will likely affect the image of the self with strong psychological consequences. Its diagnosis is confirmed by 17OH-progesterone dosages exceeding the cut-off value of 10/15 ng/ml but genotyping is progressively assuming an essential role in the study of these patients particularly in confirming difficult cases, determining some aspects of the prognosis and allowing a correct genetic counseling. Genotyping is a difficult process due to the occurrence of both a gene and a highly homologous pseudo gene. However, new tools are opening new possibilities to this analysis and improving the chances of a correct diagnosis and better understanding of the underlying mechanisms of the disease. Beyond the 10 classic pathogenic variants usually searched for in most laboratories, a correct analysis of 21OH-deficiency cases implies completely sequencing of the entire gene and the determination of gene duplications. These are now recognized to occur frequently and can be responsible for some false positive cases. And finally, because gene conversions can include several pathogenic variants one cannot be certain of identifying that both alleles are affected without studying parental DNA samples. A complete genotype characterization should be considered essential in the preparation for pregnancy, even in the case of parents with milder forms of the disease, or even just carriers, since it has been reported that giving birth to progeny with the severe classic forms occurs with a much higher frequency than expected.