RESUMO
BACKGROUND: The most common cause of hyperandrogenism in women is polycystic ovary syndrome (PCOS), the prevalence of which among women of reproductive age ranges from 8.0 to 21%. The clinical manifestations of PCOS are diverse, and the degree of metabolic and hormonal disorders depends on the PCOS phenotype. The non-classic congenital adrenal hyperplasia (NCCAH) ranks second in the structure of diseases associated with hyperandrogenism. PCOS and NCCAH have a similar clinical picture and laboratory parameters, which requires differential diagnosis. METHODS: Urinary steroid profiles were studied by gas chromatography-mass spectrometry. RESULTS: We revealed differences in glucocorticoid and androgen metabolism in women with different PCOS phenotypes, which is reflected in the clinical manifestation of the disease. It was evaluated the activity of enzymes involved in the metabolism of steroid hormones. In patients with NCCAH, it was found that polycystic ovarian changes are secondary and develop due to the presence of prolonged adrenal hyperandrogenism. CONCLUSIONS: The results obtained are important for understanding the mechanisms of disorders in various variants of hyperandrogenism and determining further tactics for managing patients.
RESUMO
Metformin is an oral hypoglycemic agent widely used in clinical practice for treatment of patients with type 2 diabetes mellitus (T2DM). The wide interindividual variability of response to metformin therapy was shown, and recently the impact of several genetic variants was reported. To assess the independent and combined effect of the genetic polymorphism on glycemic response to metformin, we performed an association analysis of the variants in ATM, SLC22A1, SLC47A1, and SLC2A2 genes with metformin response in 299 patients with T2DM. Likewise, the distribution of allele and genotype frequencies of the studied gene variants was analyzed in an extended group of patients with T2DM (n = 464) and a population group (n = 129). According to our results, one variant, rs12208357 in the SLC22A1 gene, had a significant impact on response to metformin in T2DM patients. Carriers of TT genotype and T allele had a lower response to metformin compared to carriers of CC/CT genotypes and C allele (p-value = 0.0246, p-value = 0.0059, respectively). To identify the parameters that had the greatest importance for the prediction of the therapy response to metformin, we next built a set of machine learning models, based on the various combinations of genetic and phenotypic characteristics. The model based on a set of four parameters, including gender, rs12208357 genotype, familial T2DM background, and waist-hip ratio (WHR) showed the highest prediction accuracy for the response to metformin therapy in patients with T2DM (AUC = 0.62 in cross-validation). Further pharmacogenetic studies may aid in the discovery of the fundamental mechanisms of type 2 diabetes, the identification of new drug targets, and finally, it could advance the development of personalized treatment.