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.
The objective of this study was to determine uterine fibroids (UF) prevalence in the unselected (medically unbiased) female population in the Eastern Siberia region, Russia, and to evaluate the significant risk factors. Methods and Results: The study included 2389 women aged from 18 to 80 yrs (mean age of 42.8±11.9 yrs). Subjects were evaluated consecutively by means of questionnaires, anthropometry, vital signs, gynecological examination, and pelvic ultrasound. We demonstrated 26.41% UF prevalence in the unselected female population from Eastern Siberia. We found that the single nodules predominate among all fibroids, with the types 3–5 and the size of either ≤1 cm or ≥4 cm as the most frequent variants. Our study confirmed that the prevalence of fibroids increases with age. The incidence of fibroids is significantly lower in women with the age at menarche of 15 years. We also have found that a BMI of more than 25 kg/m2, more than 4 pregnancies, and late menopause are risk factors for the development of fibroids.
The objective of our study was to investigate the specific features of immune status indicators in women of reproductive age with chronic endometritis (CE) and reproductive disorders. Methods and Results: The observational study involved 81 women of reproductive age with reproductive disorders. The main group (MG) included 50 women with CE (mean age of 29.2±5.34 years). The control group (CG) consisted of 31 fertile women also of reproductive age(mean age of 30.7 ± 5.9 years). MG was divided into the following subgroups: Subgroup A (SubA) included 31 patients with verified CE and an isolated infectious agent from endometrial tissue: Subgroup B (SubB) included 19 patients with verified CE and the absence of an infectious agent in the endometrial tissue. Endometrial aspiration pipe biopsy was performed on days 4-9 of the menstrual cycle (middle proliferative phase) using a disposable intrauterine probe (Taizhou Kechuang Medical Apparatus Co., Ltd, China) followed by histological examination of endometrial tissue. Laboratory diagnostics for sexually transmitted infections (STIs) was performed using the bacterial culture method. For the diagnosis of viral infection (HPV, HSV, CMV), cervical samples were studied using PCR. If STIs were detected, the patients were excluded from further research. Ultrasound examination of the pelvic organs was performed using the Aloka-5500 device with a 7MHz vaginal probe in two-dimensional visualization mode. The concentration of cytokines (IL-1β, INF-γ, TNF-α, ILs-4,6,8,10) in the endometrium was determined using the Protein Contour test systems (Saint Petersburg) and Multiskan EX ELISA Analyzer (Germany). The percentages and absolute counts of blood lymphocytes (CD3+, CD3+/CD8+/CD45+, CD19+/CD45+, and CD16+/CD56+/CD45+ cells) were determined by the method of indirect immunofluorescence with monoclonal antibodies using the BD FACSCalibur flow cytometer (USA). We found a significant increase in the blood concentrations of CD3+ cells, CD3+/CD8+/CD45+ cells, and CD19+/CD45+ cells and a decrease in the levels of CD16+/CD56+/CD45+ cells, microbicidal activity of oxygen-dependent function of neutrophils, and phagocytic activity of neutrophils, as well as a significant decrease in the levels of IgA, IgM, and IRI in MG, compared to CG. In SubA, compared to SubB, we found a significant decrease in CD3+ cells and CD19+/C45+ cells and a slight increase in immunoregulatory index. The concentrations of tissue cytokines in women of MG were characterized by a 3-fold increase in the level of pro- and anti-inflammatory cytokines (IL-1β, ILs - 4, 6, 10, and INF-γ), and a 4-fold increase in the levels of TNF-α and IL-8, compared to CG. In SubA, in comparison with SubB, a significant decrease in anti-inflammatory cytokines (ILs-4,10) and chemokine IL-8 was revealed against the background of a significant increase in the concentrations of INF–γ and TNF–α. Conclusion: The results obtained indicate changes in the reactivity of the immune system in women with reproductive disorders and chronic inflammation in the endometrium. The most pronounced changes in the local immunity indicators are observed when opportunistic pathogens are detected in the endometrial tissue.
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