Polycystic ovary syndrome and risks for COVID-19 infection: A comprehensive review : PCOS and COVID-19 relationship.

This comprehensive review aimed to evaluate the relationship between SARS-CoV-2 infection (the cause of coronavirus disease 2019, or COVID-19) and the metabolic and endocrine characteristics frequently found in women with polycystic ovary syndrome (PCOS). In the general population, COVID-19 is more severe in subjects with dyslipidemia, obesity, diabetes mellitus, and arterial hypertension. Because these conditions are comorbidities commonly associated with PCOS, it was hypothesized that women with PCOS would be at higher risk for acquiring COVID-19 and developing more severe clinical presentations. This hypothesis was confirmed in several epidemiological studies. The present review shows that women with PCOS are at 28%-50% higher risk of being infected with the SARS-CoV-2 virus at all ages and that, in these women, COVID-19 is associated with increased rates of hospitalization, morbidity, and mortality. We summarize the mechanisms of the higher risk of COVID-19 infection in women with PCOS, particularly in those with carbohydrate and lipid abnormal metabolism, hyperandrogenism, and central obesity.

Adrenal Androgen Predictive Effects on Clinical and Metabolic Abnormalities of Polycystic Ovary Syndrome.

OBJECTIVE: To examine the possible effects of adrenal prohormones in the prediction of clinical and metabolic abnormalities in women with polycystic ovary syndrome (PCOS). METHODS: The present study enrolled 299 normal cycling non-PCOS, 156 normoandrogenemic, and 474 hyperandrogenemic women with PCOS. Baseline characteristics were compared using a chi-squared test or analysis of variance (ANOVA) as appropriate. The roles of adrenal prohormones and their ratios with total testosterone in predicting co-occurring morbidities in women PCOS were evaluated using univariate and multivariate logistic regression analyses. RESULTS: Adrenal hyperandrogenism per dehydroepiandrosterone sulfate (DHEAS) levels were found in 32% of women with PCOS. In non-PCOS women, dehydroepiandrosterone (DHEA) and its sulfate had no predictive role concerning clinical, anthropometric, and metabolic parameters. In PCOS women, mainly in the hyperandrogenemic group, DHEA showed to be a significant predictor against most anthropometric-metabolic index abnormalities (odds ratio [OR] = 0.36-0.97; p < 0.05), and an increase in triglycerides (TG) levels (OR = 0.76; p = 0.006). Dehydroepiandrosterone sulfate presented a few predictive effects regarding PCOS-associated disorders. In controls, DHEAS predicted against the increase in estimated average glucose (OR= 0.38; p = 0.036). In the normoandrogenic group, it predicted against elevation in the waist/hip ratio (WHR) (OR= 0.59; p = 0.042), and in hyperandrogenemic PCOS women, it predicted against abnormality in the conicity index (CI) (OR = 0.31; p = 0.028). CONCLUSION: Dehydroepiandrosterone was shown to be a better predictor of abnormal anthropometric and biochemical parameters in women with PCOS than DHEAS. Thus, regarding adrenal prohormones, DHEA measurement, instead of DHEAS, should be preferred in PCOS management. The effects of androgen prohormones on the prediction of PCOS abnormalities are weak.

OBJETIVO: Examinar os possíveis efeitos dos pró-hormônios adrenais na predição de alterações clínicas e metabólicas em mulheres com síndrome dos ovários policísticos (SOP). MéTODOS: O presente estudo envolveu 299 mulheres com ciclos menstruais regulares e 630 mulheres com SOP, sendo 156 normoandrogenêmicas e 474 hiperandrogenêmicas. As variáveis incluídas como objeto do estudo foram comparadas entre os grupos usando o teste de qui-quadrado ou análise de variância (ANOVA, na sigla em inglês). Os impactos dos pró-hormônios adrenais e suas razões com a testosterona total na predição de comorbidades em mulheres com SOP foram determinados por regressão logística univariada e multivariada. RESULTADOS: Hiperandrogenismo adrenal foi encontrado em 32% das mulheres com SOP. Nos controles, a dehidroepiandrosterona e seu sulfato (DHEAS) não mostraram significância na predição das alterações clínicas, antropométricas e metabólicas. Em mulheres com SOP, principalmente no grupo de mulheres com hiperandrogenemia, a dehidroepiandrosterona (DHEA) mostrou ser um preditor significante da maioria das anormalidades nos índices antropométrico-metabólicos (odds ratio [OR] = 0,36­0,97; p < 0,05) e aumento nos níveis de triglicerídeos (TG) (OR = 0,76; p = 0,006). A DHEAS apresentou ter pouco valor na predição dos distúrbios associados à SOP; nas mulheres com androgênios elevados, restringiu-se à predição da elevação do índice de conicidade (IC) (OR = 0,31; p = 0,028). CONCLUSãO: A DHEA mostrou ser um melhor preditor na identificação das alterações dos parâmetros antropométricos e bioquímicos em mulheres com SOP do que o seu sulfato. Assim, em relação aos pró-hormônios adrenais, a dosagem de DHEA, em vez de DHEAS, parece ser mais útil no manejo da SOP. O papel dos pró-hormônios adrenais na predição de anormalidades antropométricas e metabólicas da SOP é limitado.

The connection of alpha-1 acid glycoprotein inflammatory marker with anthropometric, hormonal, and metabolic characteristic of women with polycystic ovary syndrome.

AIM: To investigate the connection of alpha-1 acid glycoprotein inflammatory biomarker with clinical, hormonal, and metabolic characteristics in women with polycystic ovary syndrome (PCOS) and normal cycling controls. METHODS: A cross-sectional study was conducted on 235 women with PCOS and 92 normal cycling controls attended between 2008 and 2018. Alpha-1 acid glycoprotein levels were correlated with clinical, anthropometric, anthropometric-metabolic indexes, and hormones of women with PCOS and controls. Simple and multivariate stepwise linear regression, matched for age and body mass index confounding variables, was performed. RESULTS: Alpha-1 acid glycoprotein levels were higher in women with PCOS (p = 0.0016). In controls, it was positively correlated with waist circumference, fat mass, body adiposity index, and lipid accumulation product, and negatively correlated with sex hormone-binding globulin (p < 0.005 for all comparisons). In PCOS, it was positively correlated with testosterone, most biomarkers of central adiposity, homeostatic model assessment of insulin-resistant, erythrocyte sedimentation rate, and negatively correlated with sex hormone-binding globulin, high-density lipoprotein cholesterol, glucose/insulin ratio, and lymphocytes (p < 0.055 for all comparisons). After multivariate regression in women with PCOS, alpha-1 acid glycoprotein retained a significant positive correlation with erythrocyte sedimentation rate and C-reactive protein. CONCLUSIONS: In PCOS, alpha-1 acid glycoprotein is correlated with biomarkers of adiposity, carbohydrate metabolism, and total testosterone. This inflammatory marker is also correlated with erythrocyte sedimentation rate, neutrophils, and lymphocytes, frequent markers of an inflammation state.

Morphology and Biochemistry of Ovulation.

The process of ovulation involves multiple and iterrelated genetic, biochemical, and morphological events: cessation of the proliferation of granulosa cells, resumption of oocyte meiosis, expansion of cumulus cell-oocyte complexes, digestion of the follicle wall, and extrusion of the metaphase-II oocyte. The present narrative review examines these interrelated steps in detail. The combined or isolated roles of the follicle-stimulating hormone (FSH) and luteinizing hormone (LH) are highlighted. Genes indiced by the FSH genes are relevant in the cumulus expansion, and LH-induced genes are critical for the resumption of meiosis and digestion of the follicle wall. A non-human model for follicle-wall digestion and oocyte release was provided.

O processo de ovulação envolve modificações genéticas, bioquímicas e morfológicas múltiplas e interrelacionadas: suspensão da proliferação das células da granulosa, reinício da meiose do oócito, expansão das células do complexo cumulus-oócito, digestão da parede folicular, e extrusão do oócito. Esta revisão narrativa examina em detalhes cada um desses eventos e os principais genes e proteínas envolvidos. Mais importante, a ação combinada ou isolada do hormônio folículo-estimulante (HFE) e do hormônio luteinizante (HL) é destacada. Detalha-se o papel do HFE na expansão do cumulus e do HL na digestão da parede folicular, permitindo a extrusão do oócito na superfície ovariana. Proveu-se um modelo não humano para explicar a digestão da parede folicular.

Morphology and Biochemistry of Ovulation Morfologia e bioquímica da ovulação

Abstract The process of ovulation involves multiple and iterrelated genetic, biochemical, and morphological events: cessation of the proliferation of granulosa cells, resumption of oocyte meiosis, expansion of cumulus cell-oocyte complexes, digestion of the follicle wall, and extrusion of the metaphase-II oocyte. The present narrative review examines these interrelated steps in detail. The combined or isolated roles of the folliclestimulating hormone (FSH) and luteinizing hormone (LH) are highlighted. Genes indiced by the FSH genes are relevant in the cumulus expansion, and LH-induced genes are critical for the resumption ofmeiosis and digestion of the follicle wall. A nonhuman model for follicle-wall digestion and oocyte release was provided.

Resumo O processo de ovulação envolve modificações genéticas, bioquímicas e morfológicas múltiplas e interrelacionadas: suspensão da proliferação das células da granulosa, reinício da meiose do oócito, expansão das células do complexo cumulus-oócito, digestão da parede folicular, e extrusão do oócito. Esta revisão narrativa examina em detalhes cada um desses eventos e os principais genes e proteínas envolvidos. Mais importante, a ação combinada ou isolada do hormônio folículo-estimulante (HFE) e do hormônio luteinizante (HL) é destacada. Detalha-se o papel do HFE na expansão do cumulus e do HL na digestão da parede folicular, permitindo a extrusão do oócito na superfície ovariana. Proveu-se um modelo não humano para explicar a digestão da parede folicular.

Differential Effects of Various Androgens on Polycystic Ovary Syndrome.

The hyperandrogenism in polycystic ovary syndrome (PCOS) is associated with the risk for the future development of the cardiovascular disease. The objective of the study is to verify whether different androgens have the same harmful effect. This cross-sectional study enrolled 823 women with PCOS: 627 (76.2%) with biochemical hyperandrogenism and 196 (23.8%) with normal androgen levels. The role of individual androgen was evaluated using univariate and multivariate logistic regression. In normoandrogenemic PCOS (NA-PCOS), free androgen index (FAI) predicted significant abnormality in visceral adipose index (VAI, OR=9.2, p=0.002) and dehydroepiandrosterone (DHEA) predicted against alteration in ß-cell function (OR=0.5, p=0.007). In hyperandrogenemic PCOS (HA-PCOS), FAI predicted derangements in waist triglyceride index (WTI), VAI, and lipid accumulation product (LAP) (OR ranging from 1.6 to 5.8, p<0.05). DHEA weakly predicted against VAI (OR 0.7, p=0.018), dehydroepiandrosterone sulfate (DHEAS) tended to predict against the conicity index (OR=0.7, p=0.037). After multiple regression, FAI retained significant strength to predict various anthropometric and metabolic abnormalities (OR ranging from 1.1 to 3.0, p<0.01), DHEA was kept as a protector factor against WTI, LAP, and VAI (OR ranging from 0.6 to 0.9; p<0.01) and DHEAS against the conicity index (OR=0.5, p<0.001). In conclusion, the free androgen index was the most powerful predictor of anthropometric and metabolic abnormalities of polycystic ovary syndrome. Conversely, DHEA and DHEAS demonstrated protective effects against disorders in some markers of obesity and abnormal metabolism.

The Role of Visceral Adiposity Index as Predictor of Metabolic Syndrome in Obese and Nonobese Women with Polycystic Ovary Syndrome.

Background: To evaluate anthropometric-metabolic biomarkers as predictors of metabolic syndrome (MS) in women with polycystic ovary syndrome (PCOS) with and without obesity. Methods: This was an observational cross-sectional study. Patients were classified as nonobese-PCOS (body mass index, BMI <30 kg/m2, n = 385), and obese-PCOS (BMI ≥30 kg/m2, n = 261). The anthropometric parameters waist circumference, waist/hip ratio, lean body mass, fat body mass, visceral adiposity index (VAI), lipid accumulating product, and biomarkers of glucose and lipid metabolisms were compared between groups. Binominal logistic regression analyses were performed to identify predictors of MS. Results: Obesity was diagnosed in 40% of all PCOS women (P < 0.001). Blood pressure and anthropometric abnormalities were significantly more frequent in obese-PCOS women (P < 0.001, for all comparisons). Glucose metabolism markers were higher in obese-PCOS compared with nonobese-PCOS (P < 0.001, for all comparisons). High-density lipoprotein cholesterol was lower in obese group than in nonobese group (1.26 mM vs. 1.08 mM, P < 0.001). MS was found in 23 of 385 (6%) nonobese-PCOS and in 116 of 261 (44.4%) obese-PCOS (P < 0.001). VAI was the best predictor of MS in both nonobese-PCOS (OR = 4.1, 95% CI 1.5-11.1) and obese-PCOS (OR = 12.9, 95% CI 5.7-29.0). Conclusions: MS is more prevalent in PCOS women with obesity. VAI was the strongest predictor of MS in both obese and nonobese PCOS women, and can be applied in clinical practice for early detection of risk for MS and precocious intervention in women with PCOS, particularly in obese women.

Comparison of metabolic and obesity biomarkers between adolescent and adult women with polycystic ovary syndrome.

PURPOSE: Knowledge of adolescent and adult phenotypes of women with polycystic ovary syndrome (PCOS) might drive opportune management. The aim of this study was to compare metabolic and obesity biomarkers between adolescent and adult women with PCOS. METHODS: This observational study compared biomarkers of obesity and metabolism derangements between adolescent (n = 62) and adult (n = 248) women with PCOS. Predictors of metabolic syndrome (MS) were investigated using univariate and multivariate binary logistic regression analysis. RESULTS: The postmenarcheal age of adolescents was 4.9 ± 0.03 years. Systolic blood pressure was lower in adolescents than in adults (112.3 mmHg vs 117.0 mmHg, p = 0.001) Diastolic blood pressure was also lower in adolescents (70.7 mmHg vs 75.8 mmHg, p < 0.001). Glucose intolerance (12.0% vs 19.3%) and insulin resistance (18.2% vs 17.7%) were similar in both groups (p > 0.05, for comparisons). Impaired fasting glucose was lower in adolescents (1.8% vs 11.6%, p = 0.015). Total cholesterol and low-density lipoprotein cholesterol were lower in adolescents (p < 0.001). MS in adolescents and adults were found in 10.3% and 27.8%, respectively (p = 0.005). Visceral adiposity index (VAI) was a good predictor of MS in both adolescents (OR = 12.2), and adults (OR = 9.7). CONCLUSIONS: Most biomarkers of glucose metabolism abnormalities were similar in adolescents and adults with PCOS. The prevalence of MS was lower in adolescents. VAI was a strong predictor of metabolic syndrome, both in adolescent and adult women with PCOS.

Exploring the activity of the enzyme 11ß-hydroxylase in the polycystic ovary syndrome.

Background Hyperandrogenemic polycystic ovary syndrome (PCOS) may have occult corticosteroidogenic enzyme abnormalities. The current study compares the activities of 11ß-hydroxylase between normoandrogenemic PCOS (NA-PCOS) and hyperandrogenemic PCOS (HA-PCOS) phenotypes. Materials and methods Anthropometric, and biochemical variables were compared between normal cycling women [n = 272] and those with PCOS [n = 453]; either normoandrogenemic [n = 98] or hyperandrogenemic [n = 355]. Univariate and multivariate logistic regression analyses were performed using 11ß-hydroxylase enzyme activity as the criterion variable. Results 11ß-Hydroxylase enzyme activity tended to be slightly higher in both PCOS subgroups and did not change with ethnicity. Using univariate logistic regression, 11ß-hydroxylase activity in controls was associated with dehydroepiandrosterone, insulin, homeostatic model for insulin resistance (HOMA-IR), and high-density lipoprotein cholesterol (HDL-C). In NA-PCOS women the activity of 11ß-hydroxylase was associated with estradiol (E2), androstenedione (A4), and androstenedione/dehydroepiandrosterone ratio; in the hyperandrogenemic (HA-PCOS) group, 11ß-hydroxylase activity associated with sex-hormone binding globulin (SHBG), 17-hydroxypregnenolone (17-OHPE), fasting glucose, and ß-cell activity. After multivariate logistic regression, androstenedione/dehydroepiandrosterone ratio, and ß-cell activity were the best predictors of 11ß-hydroxylase activity in controls; in NA-PCOS group only androstenedione/dehydroepiandrosterone ratio was confirmed as a significant predictor of 11ß-hydroxylase activity, and in HA-PCOS patients, 17-OHPE and ß-cell activity demonstrated to be significant predictors. Conclusions 11ß-Hydroxylase activity was equal in different ethnicities. The prevalence of decreased 11ß-hydroxylase activity was higher in the HA-PCOS phenotype. 17-OHPE, and ß-cell function are significant predictors of 11ß-hydroxylase activity in HA-PCOS subjects. These findings may help to identify which PCOS patient would have benefit in measuring 11-deoxycortisol (compound S) and 11ß-hydroxylase enzyme activity.

Changes in clinical and biochemical characteristics of polycystic ovary syndrome with advancing age.

OBJECTIVE: To verify whether aging can modify the clinical and biochemical characteristics of women with polycystic ovary syndrome (PCOS). MATERIAL AND METHODS: This observational cross-sectional study was conducted at the reproductive endocrinology clinics of Julio Muller University Hospital and Tropical Institute of Reproductive Medicine in Cuiabá, MT, Brazil, between 2003 and 2017. Both, 796 PCOS and 444 non-PCOS normal cycling women underwent the same examination. PCOS was diagnosed using the Rotterdam criteria as recommended for adolescent and adult subjects. Anthropometric, metabolic, and endocrinological modifications with aging were initially examined in the two groups: control and PCOS. Further analyses were performed after a 5-year age stratification of data throughout the reproductive period. All participants signed a consent form approved by the local ethical committee. RESULTS: Biomarkers of adiposity were more remarkable in African descendant PCOS women. Body weight, waist/hip ratio, fat mass, and BMI were higher in PCOS women and tended to increase at all 5 age-strata, between ≤19 and 35 years of age. Serum androgen levels decreased with aging, markedly in PCOS subjects (P < 0.01 for all age-strata comparisons), but remained elevated when compared with the levels found in controls. Carbohydrate markers, triglycerides, and total cholesterol tended to increase over time in PCOS (P < 0.01 for all age-strata comparisons). Total cholesterol also tended to increase with age in non-PCOS women (P = 0.041). CONCLUSION: The present study has shown that the advancing age influences many features of PCOS women. Biochemical hyperandrogenism, the core criterion recommended in the current systems to define the syndrome, showed statistically significant tendencies to decrease with aging progression but did not normalize. The use of age-adjusted features for the diagnosis of PCOS are recommended.

Relationship of Biological Markers of Body Fat Distribution and Corticosteroidogenic Enzyme Activities in Women with Polycystic Ovary Syndrome.

The aim of the study is to determine the impact of different anthropometric measurements of fat distribution on baseline sex-steroid concentrations and corticosteroidogenic enzyme activity in women with polycystic ovary syndrome compared to those with regular menstrual cycles. The current cross-sectional study included 106 normal cycling controls and 268 polycystic ovary syndrome patients. Patients with polycystic ovary syndrome, diagnosed by Rotterdam criteria, were divided in normoandrogenemic (n=91) and hyperandrogenemic (n=177). Anthropometric, biochemical, and hormone parameters were assessed and correlated with corticosteroidogenic enzyme activities in all three groups. Corticosteroidogenic enzyme activities were calculated using product-to-precursor ratios. Regarding sex-steroids individually, anthropometric parameters correlated with the concentrations of several androgens in polycystic ovary syndrome patients, most of them in patients with biochemical hyperandrogenism. The androgen precursors androstenedione, 17-hydroxyprogesterone, and dehydroepiandrosterone were less correlated with anthropometric parameters. The 17,20 lyase activity, in both Δ4 and Δ5 pathways, correlated with several anthropometric measurements in normo- and hyperandrogenemic polycystic ovary syndrome patients. The 17,20 lyase enzyme activity (Δ4 pathway) also correlated with conicity index, visceral adiposity index, and lipid accumulation product in the control group. 17-Hydroxylase activity positively correlated with waist-height ratio in both polycystic ovary syndrome groups. In contrast, 17-hydroxilase negatively correlated with the conicity index. Anthropometric markers of adiposity are associated with androgen levels and their precursors in blood. Body fat distribution correlates with the activities of some steroidogenic enzyme in both normo-and hyperandrogenemic polycystic ovary syndrome phenotypes. The molecular mechanisms involved in these associations are largely unclear and more investigations are required.

The Role of C-Peptide as Marker of Cardiometabolic Risk in Women With Polycystic Ovary Syndrome: A Controlled Study.

BACKGROUND: The aim of this study was to examine the role of C-peptide as a biological marker of cardiometabolic risk in polycystic ovary syndrome (PCOS). METHODS: This case-control study enrolled 385 PCOS patients and 240 normal cycling women. Anthropometric and clinical variables were taken at first visit. Fasting C-peptide, glucose, lipids, and hormone measurements were performed. Simple and multiple correlations between C-peptide and other variables associated with dysmetabolism and cardiovascular disease were examined. RESULTS: C-peptide was well correlated with several anthropometric, metabolic, and endocrine parameters. In PCOS patients, stepwise multiple regression including C-peptide as the criterion variable and other predictors of cardiovascular disease risk provided a significant model in which the fasting C-peptide/glucose ratio, glucose, body weight, and free estrogen index (FEI) were retained (adjusted R2 = 0.988, F = 7.161, P = 0.008). CONCLUSION: C-peptide levels alone or combined with C-peptide/glucose ratio, glucose, body weight, and FEI provided a significant model to identify PCOS patients with higher risk of future cardiometabolic diseases.

Combined Oral Contraceptive Effects on Low-Grade Chronic Inflammatory Mediators in Women with Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis.

Polycystic ovary syndrome is associated with dyslipidemia, dysglycemia, metabolic syndrome, and low-grade chronic inflammation, which increase the risks for cardiovascular disease. Combined oral contraceptives may affect the mediators of low-grade chronic inflammation with potential additive risk in PCOS patients. This meta-analysis investigates the impact of oral contraceptive on markers of chronic inflammation in PCOS patients. Pubmed, Scopus, and Cochrane database were used to search studies reporting on this matter in the target population. Twenty seven studies were selected, including a total of 838 women. The data were expressed as the standardized mean difference. The random-effects model was used to summarize effect sizes. Heterogeneity was examined using Cochran's test (Q) and I2 statistics. Most of the preparations increased C-reactive protein (CRP) in PCOS patients (p >0.001). The increase in homocysteine levels was not significant (p >0.05). Follistatin significantly increased with pills containing cyproterone acetate (p= 0.008). Interleukin-6 changes were inconsistent and plasminogen activator inhibitor-1 decreased with pills containing desogestrel, norgestimate, and drospirenone. Collectively, the results of this review indicate that oral contraceptives modify most inflammatory markers of PCOS patients. However, the clinical implications are not clear yet and future studies must consider longer follow-up and the inclusion of objective clinical parameters.