Androgen assessment is a key element for diagnosing polycystic ovary syndrome (PCOS), and defining a “normal” level of circulating androgens is critical for epidemiological studies. We determined the upper normal limits (UNLs) for androgens in a population-based group of premenopausal “healthy control” women, overall and by ethnicity (Caucasian and Asian), in the cross-sectional Eastern Siberia PCOS Epidemiology and Phenotype (ESPEP) Study (СlinicalTrials.gov ID: NCT05194384) conducted in 2016–2019. Overall, we identified a “healthy control” group consisting of 143 healthy premenopausal women without menstrual dysfunction, hirsutism, polycystic ovaries, or medical disorders. We analyzed serum total testosterone (TT) by using liquid chromatography with tandem mass spectrometry (LC-MS/MS), and DHEAS, sex-hormone-binding globulin (SHBG), TSH, prolactin, and 17-hydroxyprogesterone (17OHP) were assessed with an enzyme-linked immunosorbent assay (ELISA). The UNLs for the entire population for the TT, free androgen index (FAI), and DHEAS were determined as the 98th percentiles in healthy controls as follows: 67.3 (95% confidence interval (CI): 48.1, 76.5) ng/dl, 5.4 (3.5,14.0), and 355 (289, 371) μg/dl, respectively. The study results demonstrated that the UNLs for TT and FAI varied by ethnicity, whereas the DHEAS UNLs were comparable in the ethnicities studied.
Abnormalities in gut microbiota diversity are considered important mechanisms in metabolic disorders in polycystic ovarian syndrome (PCOS). However, the data on the association of these disorders with the PCOS phenotype remain controversial. The objectives of this study were to estimate the alpha diversity of the gut microbiota of healthy women and PCOS patients depending on phenotype. The study participants (184 premenopausal women: 63 with PCOS, 121 without PCOS) were recruited during the annual employment assessment in the Irkutsk Region and the Buryat Republic (Russia) in 2016–2019. For PCOS diagnosis, we used the Rotterdam (2003) criteria and definitions of PCOS phenotypes. Five indexes of alpha diversity (ASV, Shannon, Simpson, Chao, and ACE) were estimated for the gut microbiota in all participants using amplicon metasequencing. As a result, two out of five alpha diversity indexes showed a statistical difference between the non-PCOS and PCOS groups. We did not find a significant difference in the alpha diversity of gut microbiota in the subgroups of women with hyperandrogenic PCOS phenotypes vs non-androgenic phenotype D and the group of women with the presence of only one of the PCOS criteria. Nevertheless, “classic” PCOS phenotypes demonstrated the most significant decrease in alpha diversity compared with healthy women without any signs of PCOS.
Background There is a lack of data on the prevalence of PCOS and its phenotype in many geographic regions. Siberia is a unique region of the Russian Federation with a multi-raced population living in similar geographic and socio-economic conditions for centuries. Therefore, we considered this population optimal for epidemiological research. Objectives To determine the prevalence of PCOS and the PCOS phenotypes in unselected women in the Eastern Siberia region. Population: We performed the institution-based, cross-sectional Eastern Siberia PCOS Epidemiology & Phenotype (ESPEP) Study during 2016-2019 (СlinicalTrials.gov ID: NCT05194384) and recruited 1148 premenopausal women aged 34.3±6.3 yrs., of which 63.2% were Caucasians, 27.6% Asians, and 9.2% Mixed-race. All subjects provided written informed consent. Exclusion criteria were: current pregnancy or lactation, history of hysterectomy, bilateral oophorectomy, endometrial ablation, uterine artery embolization; and current or previous hormonal medications or insulin-sensitizers intake. The study was approved by the Institutional Ethics Committee of the Scientific Center for Family Health a Human Reproduction (Irkutsk, Russian Federation). Methods include questionnaires, anthropometry, vital signs, gynecological examination, mF-G scoring, pelvic U/S, and blood sampling. For PCOS diagnosis we used the Rotterdam (2003) criteria. Serum samples were analyzed for total testosterone (TT) using LC-MS/MS. DHEAS, SHBG, prolactin, TSH, and 17-OHP were assessed by ELISA. Free Androgen Index (FAI) was calculated (i.e. [TT/SHBG]×100). The upper normal limit (UNL) for the mF-G score was 4, as determined using a 2k-cluster analysis in the total study population. The upper normal limits (UNL) for androgens were determined from the 98th percentiles for these parameters in 143 women, identified as the "super-controls". Pearson Chi-square and Fisher exact one-tailed tests were used to comparing proportions and categorical variables. A p-value of 0.05 was considered statistically significant. Results The total prevalence of PCOS in premenopausal women from Eastern Siberia was estimated as 13.3%, with the following distribution of PCOS phenotypes: 29.1% (A), 9.9% (B), 26.2%(C), and 34.8% (D). There was no significant difference in PCOS prevalence by race: 13.4% in Caucasians, 11.0% in Asians, and 19.8% in Mixed race women (pχ2=0.07). Classic PCOS phenotype A was found in a comparable number of PCOS women (28% in Caucasians, 31.2% in Asians, and 30% in Mixed race); whereas Asian PCOS patients demonstrated the highest proportion of phenotype B (25% vs 5.6% in Caucasians and 5% in mixed-race). The number of hirsute women (with mF-G score >4) was dependent on race and reached 22%, 29%, and 36% among Caucasians, Asians, and mixed-race women, respectively (p χ2=0.001). Conclusions The results of the ESPEP study, conducted in a multi-race unselected population of premenopausal women from Eastern Siberia demonstrated a 13.3% total prevalence of PCOS and race-dependent difference in the clinical manifestation of PCOS. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
For the metagenomic characterization of potential taxonomic and functional diversity of microorganisms associated with polycystic ovary syndrome (PCOS) in women, we surveyed five women with PCOS and collected samples of feces, saliva, and serum. After quality processing, we have obtained from 915,594 to 3,880,379 reads; these 16,693 sequences had ribosomal RNA genes, 2,091,990 sequences contained predicted proteins with known functions, and 3,750,261 sequences had predicted proteins with unknown functions. Host DNA accounted for ca. 0.03% and less in datasets of fecal samples, from 1.41 to 24.94% in saliva samples; the remaining sequences were attributed to archaeal, bacterial, or viral DNA. In serum, from 38.18 to 75.77% were characterized as fragments of the human genome, but the remaining sequences were unidentified. Among microbes, a total of one archaeal and eight bacterial phyla were revealed. Viral DNA was detected in several fecal and one saliva sample and was classified as C2likevirus, Flavivirus, and Streptococcus bacteriophage. The metagenome sequence data were deposited at NCBI SRA as BioProject No. PRJNA625611.
The purpose of the review was to systematize the available data on the epidemiology and diagnosis of the metabolic syndrome (MetS) in polycystic ovary syndrome (PCOS). The information search was conducted using Internet resources (PubMed, EMBASE, Google Scholar, E-Library) and literature sources for the years 2000-2020. The modern studies indicate that the prevalence of metabolic disorders varies in groups of women with different PCOS phenotypes. Numerous risk factors in PCOS lead to a significant increase in risk for cardiovascular diseases. Patients with PCOS diagnosed according to AE-PCOS Society criteria have the most severe metabolic features and risk of cardiovascular disease. Hyperandrogenism in PCOS is closely related to the aggravation of abdominal obesity, and together with insulin resistance forms the metabolic core for the development of cardiovascular diseases.
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