Relevance: Mitochondrial dysfunction and systemic inflammation are believed to play pivotal role in the pathogenesis of polycystic ovary syndrome (PCOS) and related complications of metabolic disorders in adult patients. Though such researches are limited or almost absent in adolescents. The aim of the study is to evaluate the impact of mitochondrial dysfunction and systemic inflammation on PCOS pathogenesis during adolescence with regard to body mass index and insulin resistance. Design: a case-control study. Methods: The study included 95 adolescent girls (15 to 17 years old inclusive) diagnosed with PCOS based on the Rotterdam criteria. The control group consisted of 30 healthy girls of the same age with a regular menstrual cycle. All participants were subjected to a full clinical and instrumental examination, as well as an assessment of the levels of leptin, C-reactive protein (CRP), and malondialdehyde (MDA) as oxidative stress marker. Serum levels of IL-6, IL-10, IL-18, TNF-α, and plasma concentrations of macrophage migration inhibitory factor (MIF), sFas, and sFasL were determined. Patients with PCOS were divided into groups according to the presence of metabolic disorders (MD) (impaired glucose tolerance and/or over insulin resistance) and normal weight or excessive weight (NW or OW). Results: Patients with PCOS of NW in the absence of metabolic disorders (MD−/NW) had a lower concentration of MDA and a higher level of IL-10 compared to healthy girls (p < 0.05). The group (MD−/NW) was characterized with lower levels of CRP, leptin, MDA, and higher levels of sFasL, when compared to OW patients with PCOS in the absence of metabolic disorders (MD−/OW) (p < 0.05). Overweight adolescent girls with PCOS and metabolic disorders (MD+/OW) showed higher CRP, leptin, and a two-fold increase in IL-6 and IL-18 concentrations compared to the control group of healthy girls (p < 0.05 for all parameters). The group (MD+/OW) was also characterized with higher levels of CRP, leptin, MDA, IL-18, MIF (p < 0.05), when compared to overweight patients with PCOS in the absence of metabolic disorders (MD−/NW). In comparison with the MD−/OW group, the obese insulin resistant girls with PCOS (MD+/OW) had a highera level of IL-18 (p < 0.05). Moreover, the MD+/OW girls demonstrated a significant increase in CRP, MDA and IL-18 levels when compared to the MD+/NW group (p < 0.05). OW girls with PCOS without MD (MD−/OW) had lower concentrations of sFasL compared to healthy girls (p < 0.05), and higher levels of MDA compared to MD+/NW (p < 0.05). Adolescent girls of NW with PCOS and with MD (MD+/NW) had lower levels of MDA compared to the control group of healthy girls (p < 0.05). These data are confirmed by a correlation analysis and two-factor ANOVA test. Conclusions: Lean girls with PCOS demonstrate the protective mechanism of decrease in oxidative stress mediated by the activation of antioxidant defense, reduction of lipid peroxidation and systemic inflammation. Excessive weight and metabolic disorders in adolescents with PCOS are the most significant factors in reducing the capacity of antioxidant systems, activation of oxidative stress, mitochondrial dysfunction, and systemic inflammation.

Relevance: The clinical picture of polycystic ovary syndrome (PCOS) is extremely polymorphic, especially in adolescence. At the same time, the diagnostic criteria of PCOS in adolescence are still under discussion, and the hormonal parameters, including anti-Mullerian hormone range and hyperandrogenism, are not determined. The aim of the present study was to characterize the pivotal clinical and hormonal features of PCOS in adolescents and to establish the age-specific thresholds of the most essential hormonal parameters. Design: A case-control study. Methods: The study included 130 girls with PCOS according to the complete Rotterdam criteria, aged 15 to 17 years. The control group consisted of 30 healthy girls with a regular menstrual cycle of the same age. A complete clinical and laboratory examination, hormonal assays, and ultrasound of the pelvic organs were performed. The serums anti-Mullerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), LH/FSH, prolactin, estradiol, 17α-OH progesterone (17α-OHP), androstenedione, testosterone (T), dehydroepiandrosterone sulfate (DHEAS), sex hormone-binding globulin (SHBG), leptin, and free androgen index (FAI) were analyzed. The diagnostic accuracy of AMH, FAI, LH/FSH, T, and androstenedione levels in predicting PCOS in adolescents was established using a logistic regression model and calculating area under the receiver operator characteristic (ROC) curve (AUC). Results: The serum levels of LH (9.0 (5.4–13.8) vs. 3.7 (2.5–4.7) IU/L; p < 0.0001), LH/FSH (1.6 (1.0–2.3) vs. 0.7 (0.5–1.1); p < 0.0001), 17α–OHP (4.1 (3.2–5.1) vs. 3.4 (2.7–3.8) nmol/L; p = 0.0071), cortisol (464.0 ± 147.6 vs. 284.0 ± 129.7 nmol/L; p < 0.0001), prolactin (266.0 (175.0–405.0) vs. 189.0 (142.0–269.0) mIU/L; p = 0.0141), T (1.9 (1.2–2.5) vs. 0.8 (0.7–1.1) nmol/L; p < 0.0001), androstenedione (15.8 (11.6–23.2) vs. 8.3 (6.5–10.8) ng/mL; p < 0.0001), AMH (9.5 (7.5–14.9) vs. 5.8 (3.8–6.9) ng/mL; p < 0.0001), FAI (5.5 (2.8–7.0) vs. 1.6 (1.1–2.3); p < 0.0001), SHBG (37.0 (24.7–55.5) vs. 52.9 (39.0–67.6) nmol/L; p = 0.0136), DHEAS (6.8 ± 3.2 vs. 5.1 ± 1.5 μmol/L; p = 0.0039), and leptin (38.7 ± 27.1 vs. 23.7 ± 14.0 ng/mL; p = 0.0178) were significantly altered in the PCOS patients compared to the controls. Multivariate analysis of all studied hormonal and instrumental parameters of PCOS in adolescents revealed as the most essential: AMH level > 7.20 ng/mL, FAI > 2.75, androstenedione > 11.45 ng/mL, total T > 1.15 nmol/L, LH/FSH ratio > 1.23, and the volume of each ovary > 10.70 cm³ (for each criterion sensitivity ≥ 75.0–93.0%, specificity ≥ 83.0–93.0%). The diagnostic accuracy of PCOS determination was 90.2–91.6% with the combined use of either four detected indexes, which was significantly higher than the use of each index separately. The accuracy of PCOS diagnostics reached 92% using AMH and leptin concentrations when the value of the logistic regression function [85.73 − (1.73 × AMH) − (0.12 × Leptin)] was less than 70.72. Conclusions: The results of the study estimate the threshold for AMH, FAI, androstenedione, testosterone, LH/FSH, and ovarian volume, which could be suggested for use in the PCOS diagnostics in adolescents with a high sensitivity and specificity. Moreover, the combination of either four determined indexes improved the diagnostic accuracy for the PCOS detection in adolescents.

Background: A woman’s entry into the menopause period is associated with a number of changes in the body, including those related to the immune system. Immune aging is a consequence of age-related changes in the function of immune cells and the composition of their subpopulations. Menopausal hormone therapy (MHT) is thought to partially neutralize the negative effects of aging on the immune system. Objective: We aimed to evaluate the effect of oral and transdermal MHT on cellular immunity parameters and cytokine profile in menopausal women. Methods: Fifty peri- and early postmenopausal women were included. Immune parameters were assessed by flow cytometry and multiplex analysis. Results: We showed that different routes of MHT administration led to significant changes in monocyte phenotype and a decrease in monocyte chemoattractant protein-1 (MCP-1) level in menopausal patients. In addition, oral MHT resulted in a significant increase in NK and B cells. A significant increase in the number of T-helper cells was observed with transdermal MHT. In addition, oral MHT resulted in a significant decrease in IL-1β level. Conclusions: We have demonstrated for the first time that oral therapy, in contrast to transdermal therapy, has a more pronounced effect on specific immune subpopulations of blood cells in menopausal women. This effect is likely to be responsible for its anti-aging properties in the context of immune aging as well as its protective effects in infectious diseases. Perhaps testing blood immune parameters or assessing immune status before prescribing MHT could become a routine step in clinical practice before choosing a patient management strategy.

A comparative analysis of the cell surface markers and immunological properties of cell cultures originating from normal endometrium and endometrioid heterotopias of women with extragenital endometriosis was carried out. Both types of cell cultures expressed surface molecules typical of mesenchymal stromal cells and did not express hematopoietic and epithelial markers. Despite similar phenotype, the mesenchymal stromal cells derived from the two sources had different immunomodulation capacities: the cells of endometrioid heterotopias but not eutopic endometrium could suppress dendritic cell differentiation from monocytes as well as lymphocyte proliferation in allogeneic co-cultures. A comparative multiplex analysis of the secretomes revealed a significant increase in the secretion of pro-inflammatory mediators, including IL6, IFN-γ, and several chemokines associated with inflammation by the stromal cells of ectopic lesions. The results demonstrate that the stromal cells of endometrioid heterotopias display enhanced pro-inflammatory and immunosuppressive activities, which most likely impact the pathogenesis and progression of the disease.