Riscos de infecção por SARS-CoV-2 e COVID-19 em mulheres com síndrome dos ovários policísticos / Risks of SARS-CoV-2 and COVID-19 infection in women with polycystic ovary syndrome

Esta revisão narrativa teve como objetivo avaliar possíveis riscos da associação entre a infecção por SARS-CoV-2 (causa da COVID-19) e as características metabólicas e endócrinas frequentemente encontradas em mulheres com a síndrome dos ovários policísticos (SOP). A COVID-19 é mais grave em indivíduos com obesidade, diabetes mellitus, dislipidemia e hipertensão arterial. Como essas condições são comorbidades comumente associadas à SOP, foi hipotetizado que mulheres com SOP teriam maior risco de adquirir COVID-19 e desenvolver formas clínicas mais graves da doença. Considerando vários estudos epidemiológicos, a presente revisão mostra que mulheres com SOP têm risco 28% a 50% maior de serem infectadas pelo vírus SARS-CoV-2 em todas as idades e que, nessas mulheres, a COVID-19 está associada a maiores taxas de hospitalização, morbidade e mortalidade, especialmente naquelas com alterações no metabolismo de carboidratos e lipídios, hiperandrogenemia e aumento do tecido adiposo visceral. Os mecanismos que explicam o maior risco de infecção por COVID-19 em mulheres com SOP são considerados.(AU)

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.

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.

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 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.

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.

Differential activity of the corticosteroidogenic enzymes in normal cycling women and women with polycystic ovary syndrome.

The phenotypic complex of patients with definitive diagnosis of polycystic ovary syndrome may include patients with normal and high serum androgen levels. Patients with hyperandrogenemia seem to present higher risk of changes to the glucose and lipid metabolism and, eventually, of earlier development of cardiovascular diseases than normoandrogenemic patients or healthy women. From a laboratory and clinical point of view, it is important to check androgen levels in patients with polycystic ovary syndrome. The identification of partial insufficiency of a given corticosteroidogenic enzyme is also relevant to understand the physiopathology of androgen increase in polycystic ovary syndrome. Therefore, the present review analyzes the functions of the different enzymes involved in the ovary and adrenal steroidogenesis in normal cycling women and in patients with polycystic ovary syndrome. In addition, it emphasizes appropriate reason for investigating eventual enzyme deficiency to provide rationale for prescription and follow-up of women with polycystic ovary syndrome.

Subclinical Hypothyroidism Impact on the Characteristics of Patients with Polycystic Ovary Syndrome. A Meta-Analysis of Observational Studies.

BACKGROUND/AIMS: Definitive polycystic ovary syndrome (PCOS) diagnosis should exclude thyroid dysfunctions. The purpose of the study is to examine the impact of subclinical hypothyroidism on the characteristics of PCOS patients. METHODS: A meta-analysis of the published observational studies was conducted. Medline, Scopus, and Cochrane database search was performed to identify the studies that compared euthyroid PCOS and subclinical hypothyroidism (SCH)-PCOS patients. A total of 9 studies were selected, totalizing the inclusion of 1,537 euthyroid PCOS and 301 SCH-PCOS. The data were expressed as raw mean difference and standard error, using the random-effects model. Heterogeneity among studies was examined using the Cochran's test (Q) and I2 statistics. RESULTS: Anthropometrical parameters were similar in both groups. Total cholesterol (TC) and triglyceride (TG) were higher in SCH-PCOS (p = 0.036 and p = 0.012). High-density lipoprotein cholesterol was lower in the SCH-PCOS group (p = 0.018). Fasting glucose was lower in euthyroid PCOS (p = 0.022). All androgen levels were similar in both group (p > 0.05 for all). CONCLUSION: TC, TG and fasting glucose were higher in SCH-PCOS patients. Because of the heterogeneity among studies, some summarized results should be interpreted with caution. Consistent data for future studies addressing PCOS diagnosis are provided.

Comparison of steroidogenic pathways among normoandrogenic and hyperandrogenic polycystic ovary syndrome patients and normal cycling women.

AIM: To compare the corticosteroidogenic enzyme activities between normal cycling non-polycystic ovary syndrome (PCOS), and normoandrogenic PCOS (NA-PCOS) and hyperandrogenic PCOS (HA-PCOS) patients. METHODS: This cohort study was conducted at Julio Muller University Hospital and Tropical Institute of Reproductive Medicine and Menopause, and enrolled 114 non-PCOS women and 355 PCOS patients. The steroidogenic enzyme activities were measured using the serum steroid product/precursor molar ratio. RESULTS: In the Δ5 pathway the 17,20 lyase activity was equally low in the NA-PCOS and HA-PCOS women compared with the non-PCOS women (P < 0.01 and P < 0.001, respectively). In the Δ4 pathway, the 17,20 lyase activity was higher only in the HA-PCOS group (P < 0.001). The 17-hydroxylase activity was the same in PCOS and non-PCOS subjects (P > 0.05). The 3ß-hydroxysteroid dehydrogenase II (3ß-HSDII) activity was higher in the conversion of dehydroepiandrosterone into androstenedione in the HA-PCOS than in the NA-PCOS (P < 0.05) and the non-PCOS patients (P < 0.01). The aromatase activity was lower in the HA-PCOS than in the NA-PCOS (P < 0.05) patients and non-PCOS subjects (P < 0.01). In HA-PCOS subjects, the 17,20 lyase activity was related to insulin, estradiol, total testosterone concentrations and free androgen index in the Δ5 pathway. 3ß-HSDII showed weak correlation with estradiol in the HA-PCOS group. Anthropometric parameters had little impact, if any, on the steroidogenic enzyme activities. CONCLUSION: The NA-PCOS and HA-PCOS patients demonstrated different enzyme activities, and the results provided new directions for future studies including PCOS patients with different phenotypes.

New insights into steroidogenesis in normo- and hyperandrogenic polycystic ovary syndrome patients.

OBJECTIVE: This study sought to examine corticosteroidogenic enzyme activities in normo- and hyperandrogenic polycystic ovary syndrome (PCOS) patients. SUBJECTS AND METHODS: This cohort study included 81 patients with biochemical hyperandrogenism and 41 patients with normal androgen levels. Enzyme activities were assessed according to the serum steroid product/precursor ratios at baseline and after adrenal stimulation. RESULTS: At baseline, in the delta 4 (Δ4) pathway, hyperandrogenic patients showed greater 17-hydroxylase and 17,20 lyase activities in converting progesterone (P4) into 17-hydroxyprogesterone (17-OHP4) and 17-hydroxypregnenolone (17-OHPE) into androstenedione (A) (p = 0.0005 and p = 0.047, respectively) compared to normoandrogenic patients. In the delta 5 (Δ5) pathway, the 17-hydroxylase and 17,20 lyase enzymes showed similar activities in both groups. Hyperandrogenic patients presented lower 21-hydroxylase, lower 11ß-hydroxylase (p = 0.0001), and statistically significant increases in 3ß-hydroxysteroid dehydrogenase II (3ß-HSDII) activities (p < 0.0001). Following tetracosactrin stimulation, only the 17,20 lyase activity remained up-regulated in the Δ4 pathway (p < 0.0001). CONCLUSION: Hyperandrogenic patients had higher 17,20 lyase activity, both at baseline and after adrenal stimulation. Greater conversion of dehydroepiandrosterone (DHEA) into A with normal conversion of 17-OHPE to 17-OHP4 in hyperandrogenic PCOS patients indicated different levels of 3ß-HSDII activity in adrenal cells, and hyperandrogenic patients had lower 11ß-hydroxylase and 21-hydroxylase activities.

New insights into steroidogenesis in normo- and hyperandrogenic polycystic ovary syndrome patients / Novos aspectos na esteroidogênese em pacientes normo ou hiperandrogênicas com síndrome de ovários policísticos

OBJECTIVE: This study sought to examine corticosteroidogenic enzyme activities in normo- and hyperandrogenic polycystic ovary syndrome (PCOS) patients. SUBJECTS AND METHODS: This cohort study included 81 patients with biochemical hyperandrogenism and 41 patients with normal androgen levels. Enzyme activities were assessed according to the serum steroid product/precursor ratios at baseline and after adrenal stimulation. RESULTS: At baseline, in the delta 4 (Δ4) pathway, hyperandrogenic patients showed greater 17-hydroxylase and 17,20 lyase activities in converting progesterone (P4) into 17-hydroxyprogesterone (17-OHP4) and 17-hydroxypregnenolone (17-OHPE) into androstenedione (A) (p = 0.0005 and p = 0.047, respectively) compared to normoandrogenic patients. In the delta 5 (Δ5) pathway, the 17-hydroxylase and 17,20 lyase enzymes showed similar activities in both groups. Hyperandrogenic patients presented lower 21-hydroxylase, lower 11β-hydroxylase (p = 0.0001), and statistically significant increases in 3β-hydroxysteroid dehydrogenase II (3β-HSDII) activities (p < 0.0001). Following tetracosactrin stimulation, only the 17,20 lyase activity remained up-regulated in the Δ4 pathway (p < 0.0001). CONCLUSION: Hyperandrogenic patients had higher 17,20 lyase activity, both at baseline and after adrenal stimulation. Greater conversion of dehydroepiandrosterone (DHEA) into A with normal conversion of 17-OHPE to 17-OHP4 in hyperandrogenic PCOS patients indicated different levels of 3β-HSDII activity in adrenal cells, and hyperandrogenic patients had lower 11β-hydroxylase and 21-hydroxylase activities.

OBJETIVO: O objetivo deste estudo foi examinar a atividade de enzimas responsáveis pela produção de corticosteroides em pacientes normo e hiperandrogênicas com síndrome de ovários policísticos (SOP). SUJEITOS E MÉTODOS: A coorte estudada incluiu 81 pacientes com hiperandrogenismo bioquímico e 41 pacientes com níveis normais de androgênio. A atividade enzimática foi avaliada de acordo com as proporções de produto/precursor do esteroide sérico, no momento inicial do estudo e depois de estimulação adrenal. RESULTADOS: No momento inicial, na via delta 4 (Δ4), as pacientes hiperandrogênicas mostraram maior atividade da 17-hidroxilase e 17,20 liase na conversão da progesterona (P4) em 17-hidroxiprogesterona (17-OHP4) e na conversão da 17-hidroxipregnenolona (17-OHPE) em androstenediona (A) (p = 0,0005 e p = 0,047, respectivamente) em comparação com pacientes normoandrogênicas. Na via delta 5 (Δ5), a 17-hidroxilase e a 17,20 liase mostraram atividades similares nos dois grupos. As pacientes hiperandrogênicas mostraram menor atividade da 21-hidroxilase, menor atividade da 11β-hidroxilase (p = 0,0001) e aumento estatisticamente significativo na atividade da 3β-hidroxiesteroide desidrogenase II (3β-HSDII) (p < 0.0001). Após a estimulação com tetracosactrin, apenas a atividade da 17,20 liase permaneceu regulada para cima na via Δ4 (p < 0.0001). CONCLUSÃO: As pacientes hiperandrogênicas apresentaram atividade mais alta da 17,20 liase, tanto no momento inicial quanto depois da estimulação adrenal. Maior conversão da desidroepiandrosterona (DHEA) em A com conversão normal da 17-OHPE em 17-OHP4 em pacientes hiperandrogênicas com SOP indica níveis diferentes de atividade da 3β-HSDII em células da adrenal, e pacientes hiperandrogênicas apresentaram menores atividades da 11β-hidroxilase e da 21-hidroxilase.

Epidemiologia clínica do climatério / Clinical epidemiology of climacteric

Cultura, raça, hábitos e aspectos socioeconômicos exercem forte influência na sintomatologia observada durante o climatério. Os sintomas vasomotores, marcantes nas mulheres ocidentais, têm pouca relevância nas orientais e em algumas culturas indígenas. Revê-se, neste estudo, a prevalência dos fogachos, as modificações urogenitais, cardiovasculares, osteomusculares e psicocognitivas de populações bem distintas na Europa, Américas, África, Ásia e Oceania. Ainda que tenham sido menos estudadas, condições desfavoráveis na visão, audição e sistemas mastigatório e imunológico são também estimadas. Identifica-se a necessidade de estudos epidemiológicos mais abrangentes acerca das manifestações e repercussões do climatério em nosso país.

Dinâmica dos níveis do hormônio folículo estimulante na fase folicular precoce durante a vida reprodutiva / Follicle stimulating hormone dynamic during the early follicular phase

Avaliar os níveis do hormônio folículo estimulante (FSH) na fase folicular precoce durante o período reprodutivo. Cerca de 20ml de sangue venoso foram colhidos entre os dias 3 e 5 do ciclo menstrual de 246 mulheres näo selecionadas, entre 13 e 52 anos de idade, excluindo-se as que estivessem em uso de medicamentos que pudessem interferir com os níveis das gonadotrofinas. As concentraçöes de FSH e LH foram determinadas em duplicata. Regressöes linear e näo linear, polinomial, foram realizadas considerando-se as concentraçöes de FSH como variável dependente versus idade como variável independente. Os níveis de FSH elevaram-se de modo gradual em aproximadamente 2,6 vezes ao longo dos anos reprodutivos (p<0,025). Detectou-se correlaçäo positiva entre a idade e os níveis de FSH (p<0,05). A inclinaçäo da parábola pela regressäo polinomial (Y=7,97-0,009x+0,057x²) foi de 0,359 e o coeficiente de correlaçäo generalizado foi r=0,795. Um coeficiente de Pearson de r²=0,889 foi obtido por regressäo linear. A análise de melhoria do ajuste mostrou que a parábola representa melhor o fenômeno (F=4,7;p<0,05). Os níveis de LH nesta fase permaneceram quase constantes na populaçäo examinada, com pequena elevaçäo apenas a partir dos 40 anos. O FSH, verificado na fase folicular precoce do ciclo menstrual, eleva-se de modo näo linear durante os anos reprodutivos e as concentraçöes de LH permanecem quase constantes, aumentando discretamente apenas nas pacientes com idade acima de 40 anos.

Mecanismos do consumo folicular ovariano / Mechanisms of ovarian follicle depletion

Este estudo resume o conhecimento atual dos mecanismos envolvidos no consumo folicular no ovário humano. Após o desenvolvimento da gônada e início dos processos de mitose e meiose das oogônias e oócitos, o número de oócitos alcança cerca de 6 a 7 milhöes ao redor da 22ª semana de gravidez. No momento do nascimento o número de oócitos fica reduzido a 1-2 milhöes, refletindo consumo folicular na vida intra-uterina. No início da puberdade o número total de folículos foi reduzido a 400.000. A partir daí, mais de 99,9 por cento dos folículos sofrem degeneraçäo ao longo da vida e apenas 0,1 por cento destes conseguem alcançar um desenvolvimento completo e serem ovulados. Este processo de consumo folicular é um evento complexo. Na vida intra-uterina a mulher perde a maioria dos folículos formados, como resultado de uma taxa de consumo muito rápida. Enquanto gonadotrofinas e certos peptídeos intra-ovarianos atuam como fatores favoráveis à sobrevida dos oócitos nesta fase, os androgênios, um peptídio semelhante ao GnRH e a interleucina-6 säo importantes indutores da atresia. Após o nascimento há diminuiçäo na taxa de consumo folicular e durante o menacme cerca de 1000 folículos säo consumidos a cada mês. Este número é aumentado após os 38 anos de idade, parecendo resultar da aceleraçäo na taxa de crescimento folicular ou de excessiva atresia dos folículos que se encontram em estágios iniciais de desenvolvimento. A apoptose parece ser o mecanismo básico celular de degeneraçäo ou atresia folicular.