Regulation of androgen biosynthesis - A short review and preliminary results from the hyperandrogenic starvation NCI-H295R cell model

Regulation of androgen production is poorly understood. Adrenarche is the physiologic event in mid-childhood when the adrenal zona reticularis starts to produce androgens through specific expression of genes for enzymes and cofactors necessary for androgen synthesis. Similarly, expression and activities of same genes and products are deregulated in hyperandrogenic disorders such as the polycystic ovary syndrome (PCOS). Numerous studies revealed involvement of several signaling pathways stimulated through G-protein coupled receptors or growth factors transmitting their effects through cAMP- or non-cAMP-dependent signaling. Overall a complex network regulates androgen synthesis targeting involved genes and proteins at the transcriptional and post-translational levels. Newest players in the field are the DENND1A gene identified in PCOS patients and the MAPK14 which is the kinase phosphorylating CYP17 for enhanced lyase activity. Next generation sequencing studies of PCOS patients and transcriptome analysis of androgen producing tissues or cell models provide newer tools to identify modulators of androgen synthesis.

Interventions for hirsutism (excluding laser and photoepilation therapy alone)

BACKGROUND Hirsutism occurs in 5% to 10% of women of reproductive age when there is excessive terminal hair growth in androgen-sensitive areas (male pattern). It is a distressing disorder with a major impact on quality of life. The most common cause is polycystic ovary syndrome. There are many treatment options, but it is not clear which are most effective. OBJECTIVES To assess the effects of interventions (except laser and light-based therapies alone) for hirsutism. SEARCH METHODS We searched the Cochrane Skin Group Specialised Register, CENTRAL (2014, Issue 6), MEDLINE (from 1946), EMBASE (from 1974), and five trials registers, and checked reference lists of included studies for additional trials. The last search was in June 2014. SELECTION CRITERIA Randomised controlled trials (RCTs) in hirsute women with polycystic ovary syndrome, idiopathic hirsutism, or idiopathic hyperandrogenism. DATA COLLECTION AND ANALYSIS Two independent authors carried out study selection, data extraction, 'Risk of bias' assessment, and analyses. MAIN RESULTS We included 157 studies (sample size 30 to 80) comprising 10,550 women (mean age 25 years). The majority of studies (123/157) were 'high', 30 'unclear', and four 'low' risk of bias. Lack of blinding was the most frequent source of bias. Treatment duration was six to 12 months. Forty-eight studies provided no usable or retrievable data, i.e. lack of separate data for hirsute women, conference proceedings, and losses to follow-up above 40%.Primary outcomes, 'participant-reported improvement of hirsutism' and 'change in health-related quality of life', were addressed in few studies, and adverse events in only half. In most comparisons there was insufficient evidence to determine if the number of reported adverse events differed. These included known adverse events: gastrointestinal discomfort, breast tenderness, reduced libido, dry skin (flutamide and finasteride); irregular bleeding (spironolactone); nausea, diarrhoea, bloating (metformin); hot flushes, decreased libido, vaginal dryness, headaches (gonadotropin-releasing hormone (GnRH) analogues)).Clinician's evaluation of hirsutism and change in androgen levels were addressed in most comparisons, change in body mass index (BMI) and improvement of other clinical signs of hyperandrogenism in one-third of studies.The quality of evidence was moderate to very low for most outcomes.There was low quality evidence for the effect of two oral contraceptive pills (OCPs) (ethinyl estradiol + cyproterone acetate versus ethinyl estradiol + desogestrel) on change from baseline of Ferriman-Gallwey scores. The mean difference (MD) was -1.84 (95% confidence interval (CI) -3.86 to 0.18).There was very low quality evidence that flutamide 250 mg, twice daily, reduced Ferriman-Gallwey scores more effectively than placebo (MD -7.60, 95% CI -10.53 to -4.67 and MD -7.20, 95% CI -10.15 to -4.25). Participants' evaluations in one study with 20 participants confirmed these results (risk ratio (RR) 17.00, 95% CI 1.11 to 259.87).Spironolactone 100 mg daily was more effective than placebo in reducing Ferriman-Gallwey scores (MD -7.69, 95% CI -10.12 to -5.26) (low quality evidence). It showed similar effectiveness to flutamide in two studies (MD -1.90, 95% CI -5.01 to 1.21 and MD 0.49, 95% CI -1.99 to 2.97) (very low quality evidence), as well as to finasteride in two studies (MD 1.49, 95% CI -0.58 to 3.56 and MD 0.40, 95% CI -1.18 to 1.98) (low quality evidence).Although there was very low quality evidence of a difference in reduction of Ferriman-Gallwey scores for finasteride 5 mg to 7.5 mg daily versus placebo (MD -5.73, 95% CI -6.87 to -4.58), it was unlikely it was clinically meaningful. These results were reinforced by participants' assessments (RR 2.06, 95% CI 0.99 to 4.29 and RR 11.00, 95% CI 0.69 to 175.86). However, finasteride showed inconsistent results in comparisons with other treatments, and no firm conclusions could be reached.Metformin demonstrated no benefit over placebo in reduction of Ferriman-Gallwey scores (MD 0.05, 95% CI -1.02 to 1.12), but the quality of evidence was low. Results regarding the effectiveness of GnRH analogues were inconsistent, varying from minimal to important improvements.We were unable to pool data for OCPs with cyproterone acetate 20 mg to 100 mg due to clinical and methodological heterogeneity between studies. However, addition of cyproterone acetate to OCPs provided greater reductions in Ferriman-Gallwey scores.Two studies, comparing finasteride 5 mg and spironolactone 100 mg, did not show differences in participant assessments and reduction of Ferriman-Gallwey scores (low quality evidence). Ferriman-Gallwey scores from three studies comparing flutamide versus metformin could not be pooled (I² = 62%). One study comparing flutamide 250 mg twice daily with metformin 850 mg twice daily for 12 months, which reached a higher cumulative dosage than two other studies evaluating this comparison, showed flutamide to be more effective (MD -6.30, 95% CI -9.83 to -2.77) (very low quality evidence). Data showing reductions in Ferriman-Gallwey scores could not be pooled for four studies comparing finasteride with flutamide as the results were inconsistent (I² = 67%).Studies examining effects of hypocaloric diets reported reductions in BMI, but which did not result in reductions in Ferriman-Gallwey scores. Although certain cosmetic measures are commonly used, we did not identify any relevant RCTs. AUTHORS' CONCLUSIONS Treatments may need to incorporate pharmacological therapies, cosmetic procedures, and psychological support. For mild hirsutism there is evidence of limited quality that OCPs are effective. Flutamide 250 mg twice daily and spironolactone 100 mg daily appeared to be effective and safe, albeit the evidence was low to very low quality. Finasteride 5 mg daily showed inconsistent results in different comparisons, therefore no firm conclusions can be made. As the side effects of antiandrogens and finasteride are well known, these should be accounted for in any clinical decision-making. There was low quality evidence that metformin was ineffective for hirsutism and although GnRH analogues showed inconsistent results in reducing hirsutism they do have significant side effects.Further research should consist of well-designed, rigorously reported, head-to-head trials examining OCPs combined with antiandrogens or 5α-reductase inhibitor against OCP monotherapy, as well as the different antiandrogens and 5α-reductase inhibitors against each other. Outcomes should be based on standardised scales of participants' assessment of treatment efficacy, with a greater emphasis on change in quality of life as a result of treatment.

Regulation of human (adrenal) androgen biosynthesis-New insights from novel throughput technology studies

Androgens are precursors for sex steroids and are predominantly produced in the human gonads and the adrenal cortex. They are important for intrauterine and postnatal sexual development and human reproduction. Although human androgen biosynthesis has been extensively studied in the past, exact mechanisms underlying the regulation of androgen production in health and disease remain vague. Here, the knowledge on human androgen biosynthesis and regulation is reviewed with a special focus on human adrenal androgen production and the hyperandrogenic disorder of polycystic ovary syndrome (PCOS). Since human androgen regulation is highly specific without a good animal model, most studies are performed on patients harboring inborn errors of androgen biosynthesis, on human biomaterials and human (tumor) cell models. In the past, most studies used a candidate gene approach while newer studies use high throughput technologies to identify novel regulators of androgen biosynthesis. Using genome wide association studies on cohorts of patients, novel PCOS candidate genes have been recently described. Variant 2 of the DENND1A gene was found overexpressed in PCOS theca cells and confirmed to enhance androgen production. Transcriptome profiling of dissected adrenal zones established a role for BMP4 in androgen synthesis. Similarly, transcriptome analysis of human adrenal NCI-H295 cells identified novel regulators of androgen production. Kinase p38α (MAPK14) was found to phosphorylate CYP17 for enhanced 17,20 lyase activity and RARB and ANGPTL1 were detected in novel networks regulating androgens. The discovery of novel players for androgen biosynthesis is of clinical significance as it provides targets for diagnostic and therapeutic use.

Oral glucose tolerance test in children and adolescents: Positives and pitfalls

Objectives: To describe the glycaemic status (assessed by an oral glucose tolerance test (OGTT)) and associated comorbidities in a cohort of Australian children and adolescents at risk of insulin resistance and impaired glucose homeostasis (IGH). Methods: Twenty-one children and adolescents (three male, 18 female) (18 Caucasian, one Indigenous, two Asian) (20 obese, one lipodystrophy) referred to the Paediatric Endocrinology and Diabetes Clinic underwent a 2-h OGTT with plasma glucose and insulin measured at baseline, + 60 and + 120 min. If abnormal, the OGTT was repeated. Results: The mean (SD) age was 14.2 (1.6) years, BMI 38.8 (7.0) kg/m(2) and BMI-SDS 3.6 (0.6). Fourteen patients had fasting insulin levels >21 mU/L. Type 2 diabetes mellitus was diagnosed in one patient, impaired glucose tolerance (IGT) in four patients and impaired fasting glycaemia (IFG) in one patient. Despite no weight loss, only one patient had a persistently abnormal OGTT on repeat testing. Three patients with IGH were medicated with risperidone at the time of the initial OGTT. One patient who had persistent IGT had continued risperidone. The other two patients had initial OGTT results of IGT and diabetes mellitus type 2. They both ceased risperidone between tests and repeat OGTT showed normal glycaemic status. Conclusions: Use of fasting glucose alone may miss cases of IGH. Diagnosis of IGT should not be made on one test alone. Interpretation of glucose and insulin responses in young people is limited by lack of normative data. Larger studies are needed to generate Australian screening recommendations. Further assessment of the potential adverse effects of atypical antipsychotic medication on glucose homeostasis in this at-risk group is important.

Indexes of insulin resistance and secretion in obese children and adolescents

OBJECTIVE - To assess the concurrent validity of fasting indexes of insulin sensitivity and secretion in - obese prepubertal (Tanner stage 1) children and pubertal (Tanner stages 2-5) glucose tolerance test (FSIVGTT) as a criterion measure. RESEARCH DESIGN AND METHODS - Eighteen obese children and adolescents (11 girls and 7 boys, mean age 12.2 +/- 2.4 years, mean BMI 35.4 +/- 6.2 kg/m(2), mean BMI-SDS 3.5 +/- 0.5, 7 prepubertal and I I pubertal) participated in the study. All participants underwent an insulin-modified FSIVGTT on two occasions, and 15 repeated this test a third time (mean 12.9 and 12.0 weeks apart). S-i measured by the FSIVGTT was compared with homeostasis model assessment (HOMA) of insulin resistance (HOMA-IR), quantitative insulin-sensitivity check index (QUICKI), fasting glucose-to-insulin ratio (FGIR), and fasting insulin (estimates of insulin sensitivity derived from fasting samples). The acute insulin response (AIR) measured by the FSIVGTT was compared with HOMA of percent beta-cell function (HOMA-beta%), FGIR, and fasting insulin (estimates of insulin secretion derived from fasting samples). RESULTS - There was a significant negative correlation between HOMA-IR and S-i (r = -0.89, r = -0.90, and r = -0.81, P < 0.01) and a significant positive correlation between QUICKI and S-i (r = 0.89, r = 0.90, and r = 0.81, P < 0.01) at each time point. There was a significant positive correlation between FGIR and S-i (r = 0.91, r = 0.91, and r = 0.82, P < 0.01) and a significant negative correlation between fasting insulin and S-i (r = -90, r = -0.90, and r = -0.88, P < 0.01). HOMA-beta% was not as strongly correlated with AIR (r = 0.60, r = 0.54, and r = 0.61, P < 0.05). CONCLUSIONS - HOMA-IR, QUICKI, FGIR, and fasting insulin correlate strongly with S-i assessed by the FSIVGTT in obese children and adolescents. Correlations between HOMA-β% FGIR and fasting insulin, and AIR were not as strong. Indexes derived from fasting samples are a valid tool for assessing insulin sensitivity in prepubertal and pubertal obese children.

Population pharmacokinetics of metformin in late pregnancy

The pharmacokinetic disposition of metformin in late pregnancy was studied together with the level of fetal exposure at birth. Blood samples were obtained in the third trimester of pregnancy from women with gestational diabetes or type 2 diabetes, 5 had a previous diagnosis of polycystic ovary syndrome. A cord blood sample also was obtained at the delivery of some of these women, and also at delivery of others who had been taking metformin during pregnancy but from whom no blood had been taken. Plasma metformin concentrations were assayed by a new, validated, reverse-phase HPLC method, A 2-compartment, extravascular maternal model with transplacental partitioning of drug to a fetal compartment was fitted to the data. Nonlinear mixed-effects modeling was performed in'NONMEM using FOCE with INTERACTION. Variability was estimated using logarithmic interindividual and additive residual variance models; the covariance between clearance and volume was modeled simultaneously. Mean (range) metformin concentrations in cord plasma and in maternal plasma were 0.81 (range, 0.1-2.6) mg/L and 1.2 (range, 0. 1-2.9) mg/L, respectively. Typical population values (interindividual variability, CV%) for allometrically scaled maternal clearance and volume of distribution were 28 L/h/70 kg (17.1%) and 190 L/70 ka (46.3%), giving a derived population-wide half-life of 5.1 hours. The placental partition coefficient for metformin was 1.07 (36.3%). Neither maternal age nor weight significantly influenced the pharmacokinetics. The variability (SD) of observed concentrations about model-predicted concentrations was 0.32 mg/L. The pharmacokinetics were similar to those in nonpregnant patients and, therefore, no dosage adjustment is warranted. Metformin readily crosses the placenta, exposing the fetus to concentrations approaching those in the maternal circulation. The sequelae to such exposure, ea, effects on neonatal obesity and insulin resistance, remain unknown.

The effectiveness of lamotrigine in the treatment of photosensitive epilepsy

Photosensitive epilepsy and associated pattern sensitivity are more prevalent in females and are usually treated with sodium valproate. Sodium valproate has an adverse effect profile, which particularly affects females, including teratogenicity, association with the polycystic ovary syndrome and weight gain. It would be useful therefore if an alternative treatment for photosensitive epilepsy could be found. The principle aim of this study was to investigate the effectiveness of lamotrigine in the treatment of photosensitive epilepsy in adults and children. Patients were either drug-naive, commencing lamotrigine therapy or were transferring from other antiepileptic drugs to lamotrigine (primarily sodium valproate) due to lack of response, adverse effects or desired pregnancy. The photoparoxsymal response in the electroencephalograph was used as the primary measure of photo and pattern sensitivity. In addition the effects of lamotrigine on occipital spikes and normal responses in the EEG to visual stimuli were investigated. Secondary measures also included the resting EEG, seizures, body mass index, menstrual function, mood and cognitive function. The results suggest that in adult patients lamotrigine is efficacious in the treatment of photosensitive epilepsy, although it appears inferior to sodium valproate. Lamotrigine does however have a more favourable adverse effect profile than valproate. The results indicate that lamotrigine therapy is suitable for photosensitive epilepsy in women of childbearing age or in patients experiencing unacceptable adverse effects with valproate therapy. Patients are more likely to respond to lamotrigine treatment if they present with sensitivity to a limited number of frequencies. Lamotrigine does not seem to be as efficacious in the treatment of children, although against it may be considered a second line drug if the child does not respond to or will not tolerate sodium valproate.

Treatment with metformin

Metformin is an anti-hyperglycaemic agent widely used in the treatment of type 2 diabetes. It counters insulin resistance through insulin-dependent and -independent effects on cellular nutrient and energy metabolism, improving glycaemic control without weight gain and without increasing the risk of hypoglycaemia. Metformin can also benefit several risk factors for vascular disease independently of glycaemic control. In subjects with metabolic syndrome, metformin improves prognosis. It decreases progression of impaired glucose tolerance to type 2 diabetes, assists weight reduction especially in conjunction with lifestyle management and exerts other potentially favourable cardiovascular effects. For example, metformin can modestly improve the lipid profile in some dyslipidaemic individuals, reduce pro-inflammatory cytokines and monocyte adhesion molecules and decrease advanced glycation end products. Metformin can also improve parameters of endothelial function in the macro- and micro-vasculature, indicating lower athero-thrombotic risk, but it does not appear to reduce blood pressure. In normoglycaemic individuals with risk factors for diabetes and in women with polycystic ovary syndrome there is evidence that metformin can defer or prevent the development of diabetes. Thus, metformin offers beneficial effects to delay the onset and reverse or reduce the progression of many of the metabolic features and cardiovascular risk factors associated with metabolic syndrome.

Parâmetros bioquímicos e níveis de IgE total e específicas para aeroalérgenos em mulheres obesas com síndrome dos ovários policísticos

Introduction: Polycystic ovary syndrome (PCOS) whose classic features (menstrual irregularity of oligo/ amenorrhea type, chronic anovulation, infertility and hyperandrogenism clinical and/ or biochemical), is associated with aspects of metabolic syndrome (MS), as obesity and insulin resistance. The level of obesity determines different levels of inflammation, increasing cytokines participants of metabolic and endocrine functions, beyond modulate the immune response. Metabolic changes, added to the imbalance of sex hormones underlying irregular menstruation observed in (PCOS) can trigger allergic processes and elevation of total and specific IgE antibodies indicate that a sensitization process was started. Objective: To evaluate the influence of PCOS on biochemical parameters and levels of total and specific IgE to aeroallergens in obese women. Methods: After approval by the Committee of Ethics in Research, were recruited 80 volunteers with BMI ≥ 30 kg/m2 and age between 18 and 45 years. Among these, 40 with PCOS according to the Rotterdam criteria and 40 women without PCOS (control group). All participants were analysed with regard to anthropometric, clinical, gynecological parameters, interviewed using a questionnaire, and underwent blood sampling for realization of laboratory tests of clinical biochemistry: Total cholesterol, LDL-cholesterol, HDL- cholesterol, Triglycerides, Fasting glucose, Urea, Creatinine, Aspartate aminotransferase (AST), Alanine aminotransferase (ALT) and immunological: total and specific IgE to Dermatophagoides pteronyssinus, Blomia tropicalis, Dermatophagoides farinae and Dermatophagoides microceras.Statistical analysis was performed using SPSS 15.0 software through the chi-square tests, Fisher, Student t test and binary logistic regression, with significance level (p <0.05). Results: It was observed in the group of obese women with PCOS that 29 (72.5%) had menstrual cycle variable and 27 (67.5%) had difficulty getting pregnant. According to waist-hip ratio, higher average was also observed in obese PCOS (0.87). Blood level of HDL (36.9 mg/dL) and ALT (29.3 U/L) were above normal levels in obese women with PCOS, with statistically significant relationship. In the analysis of total and specific IgE to D. pteronyssinus high results were also prevalent in obese PCOS, with blood level (365,22 IU/mL) and (6.83 kU/L), respectively, also statistically significant. Conclusions: Observed predominance of cases with high levels of total IgE in the group of obese women with PCOS, 28 (70%) of the participants, whose mean blood concentration of the group was 365.22 IU/mL. In the analysis of Specific IgE between the groups, the allergen Dermatophagoides pteronyssinus showed greater dispersion and average the results of sensitization in the group of obese PCOS, whose mean blood concentration was 6.83 kU/l. Keywords: Obesity, Allergens and Polycystic Ovary Syndrome

A influência da perda de peso no perfil inflamatório de mulheres com síndrome dos ovários policísticos

The polycystic ovary syndrome (PCOS) is considered the most common endocrine disorder in reproductive age women, with a prevalence ranging from 15 to 20%. In addition to hormonal and reproductive changes, it is common in PCOS the presence of risk factors for developing cardiovascular disease (CVD) and diabetes mellitus, insulin resistance (IR), visceral obesity, chronic low-grade inflammation and dyslipidemia. Due to the high frequency of obesity associated with PCOS, weight loss is considered as the first-line treatment for the syndrome by improving metabolic and normalizes serum androgens, restoring reproductive function of these patients. Objectives: To evaluate the inflammatory markers and IR in women with PCOS and healthy ovulatory with different nutritional status and how these parameters are displayed after weight loss through caloric restriction in with Down syndrome. Methods: Tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and C-reactive protein (CRP) were assessed in serum samples from 40 women of childbearing age. The volunteers were divided into four groups: Group I (not eutrophic with PCOS, n = 12); Group II (not eutrophic without PCOS, n = 10), Group III (eutrophic with PCOS, n = 08) and Group IV (eutrophic without PCOS, n = 10). The categorization of groups was performed by body mass index (BMI), according to the World Health Organization (WHO) does not eutrophic, overweight and obesity (BMI> 25 kg / m²) and normal weight (BMI <24.9 kg / m²). IR was determined by HOMA-IR index. In the second phase of the study a controlled dietary intervention was performed and inflammatory parameters were evaluated in 21 overweight and obese women with PCOS, before and after weight loss. All patients received a low-calorie diet with reduction of 500 kcal / day of regular consumption with standard concentrations of macronutrients. Results: Phase 1: PCOS patients showed increased levels of CRP (p <0.01) and HOMAIR (p <0.01). When divided by BMI, both not eutrophic group with PCOS (I) as eutrophic with PCOS (III) showed increased levels of CRP (I = 2.35 ± 0,55mg / L and 2.63 ± III = 0,65mg / L; p <0.01) and HOMA-IR (I = 2.16 ± 2.54 and III = 1.07 ± 0.55; p <0.01). There were no differences in TNF-α and IL-6 between groups. Step 2: After the weight loss of 5% of the initial weight was reduced in all of the components of serum assessed inflammatory profile, PCR (154.75 ± 19:33) vs (78.06 ± 8.9) TNF α (10.89 ± 5.09) vs (6:39 ± 1:41) and IL6 (154.75 ± 19:33) vs (78.06 ± 08.09) (p <0:00) in association with improvement some hormonal parameters evaluated. Conclusion: PCOS contributed to the development of chronic inflammation and changes in glucose metabolism by increasing CRP, insulin and HOMA-IR, independent of nutritional status. The weight loss, caloric restriction has improved the inflammatory condition and hormonal status of the evaluated patients.

Avaliação da genotoxicidade em mulheres com síndrome dos ovários policísticos: impacto da dieta

Introduction: Polycystic Ovary Syndrome (PCOS), present in 6-12% of women of reproductive age, the criterion of Rotterdam, is characterized by hyperandrogenism, insulin resistance (IR) and its inflammatory state, exacerbated by obesity and factors associated with the increase in damage DNA. Weight loss, combined with healthy eating, acts restoring the reproductive and metabolic functions in the SOP, though its influence in reducing DNA damage in PCOS are unknown. Aim: To investigate whether there are differences between DNA damage markers and factors of cardiometabolic risk in women with PCOS and control, and evaluate the effectiveness of nutritional intervention in DNA damage markers and cardiometabolic risk markers in overweight and obese women with PCOS. Methods: the study was conducted in two studies and the participants were aged between 18 and 35 years. In the first study, a prospective case-control, were included 27 women diagnosed with PCOS and 20 controls. In the second study, clinical trial of nutritional intervention with 12-week calorie-restricted diet 500Kcal / day. The genotoxicity, DNA damage (intensity tail, tail moment and tail length) was evaluated by the comet assay. Anthropometric data, dietary intake, hormonal, biochemical and inflammatory were evaluated in different studies. Results: there was no significant difference between the DNA damage marker tail intensity (p = 0.18), tail moment (p = 0.76) and tail length (p = 0.109) in PCOS when compared to the control group. Data after nutritional intervention in PCOS women with overweight and obesity showed a decrease in DNA damage markers: tail intensity (24.35 ± 5.86 - pre-diet vs. 17.15 ± 5.04 -Post-diet) and tail moment (20.47 ± 7.85 - pre-diet vs. 14.13 ± 6.29 -post-diet) (p <0.001). Reduction of weight (3.5%) and decreased cardiometabolic markers IR and hyperandrogenism. Conclusion: women with PCOS have a worse cardiometabolic risk profile compared to control however similar genotoxicity identified by DNA damage. Nutritional intervention reduced the genotoxicity of overweight and obese women with PCOS, and reduce the factors of cardiometabolic risk.

Irregularidade do ciclo menstrual no Menacme como marcador para fatores de risco cardiovasculares na pós-menopausa

A associação entre fatores de risco cardiovascular (FRCV) na pósmenopausa e o antecedente de irregularidade menstrual no menacme foi avaliado em estudo caso-controle envolvendo 414 mulheres na pósmenopausa com idade de 60,4 ± 5,5 anos e IMC de 25,3 ± 4,7 kg/m2. As variáveis consideradas foram: caracterização do ciclo menstrual entre 20 e 35 anos (independente) e relato atual sobre ocorrência de hipertensão arterial, dislipidemia, diabetes mellitus e doença arterial coronariana (dependentes). Utilizou-se o teste qui-quadrado e modelos de regressão logística, ajustados para outras variáveis implicadas no risco para doenças CV, com nível de significância 5%. Observou-se que mulheres que relataram irregularidade menstrual prévia estiveram associadas com risco aumentado para ocorrência de algum FRCV [odds ratio ajustado (OR)= 2,14; IC-95%= 1,02–4,48], quando comparadas àquelas com ciclos regulares. Análise estratificada demonstrou as seguintes associações significativas com o antecedente de irregularidade menstrual: hipertensão arterial (OR= 2,4; 95% IC= 1,39–5,41), hipercolesterolemia (OR= 2,32; 95% IC= 1,17–4,59), hipertrigliceridemia (OR= 2,09; 95% IC= 1,10–4,33) e angioplastia coronariana (OR= 6,82; 95% IC= 1,44–32,18). Os dados sugerem que o antecedente de irregularidade menstrual, indicativo da ocorrência da síndrome dos ovários policísticos na idade reprodutiva, pode estar relacionado com aumento do risco para doenças CV na pós-menopausa __________________________________________________ABSTRACT Menstrual Cycle Irregularity as a Marker of Cardiovascular Risk Factors at Postmenopausal Years.To evaluate the association between cardiovascular risk factors (CVRF)during postmenopausal years and previous menstrual irregularity during reproductive years, we performed a case-control study in 414 postmenopausal women (mean age 60.4 ± 5.5 years; BMI 25.3 ± 4.7 kg/m2). The variables assessed were: menstrual cycle characteristics at age 20–35y (independent) and records of arterial hypertension, dyslipidemia, diabetes mellitus, and coronary heart disease (dependent). Statistical analysis used the chi-square test and logistic regression, adjusting for potential confounders for cardiovascular risk, with significance set at 5%. Women reporting previous menstrual irregularity were associated with increased risk for some CVRF [adjusted odds ratio (OR) 2.14; CI-95%= 1.02–4.48], when compared with those reporting regular menstrual cycles. Stratified analysis demonstrated significant associations of previous menstrual irregularity with: arterial hypertension [OR= 2.74; CI-95%= 1.39–5.41), hypercholesterolemia (OR= 2.32; CI-95%= 1.17–4.59), hypertriglyceridemia (OR= 2.09; CI-95%=1.10–4.33), and coronary angioplasty (OR= 6.82; CI-95%= 1.44–32.18). These data suggest that a prior history of menstrual irregularity, as indicative of polycystic ovary syndrome, may be related to increased risk for CVD during postmenopausal years

Síndrome de ovários policísticos: enfoque psicossocial

A síndrome dos ovários policísticos (SOP) é um distúrbio endócrino-ginecológico que se caracteriza, principalmente, por anovulação crónica e hiperandrogenismo, afetando entre 5 a 10% das mulheres em idade reprodutiva. As principais manifestações da SOP incluem os seguintes sintomas: irregularidade menstrual, hirsutismo, infertilidade, acne, alopecia androgenética, obesidade e acantose nigricans. Esses sintomas apresentam- se de forma bastante heterogênea, havendo diferenças marcantes na sua prevalência e intensidade entre diferentes grupos de mulheres que apresentam SOP. Apesar da condição biológica, a SOP não é apenas um problema físico, mas também psicossocial, interferindo e comprometendo a qualidade de vida das mulheres que a apresentam. A partir de uma revisão da literatura, este estudo discute os aspectos psicossociais de mulheres com SOP, destacando o impacto dos sintomas na qualidade de vida relacionada com a saúde. Considerando que cada mulher responde de forma singular aos sintomas que apresentam, destaca-se a importância de incorporar a perspectiva individual da mulher com SOP ao seu contexto social. Nesse sentido, são discutidos achados de pesquisas utilizando abordagens metodológicas quantitativas e qualitativas, numa tentativa de melhor compreender a experiência das mulheres diante da SOP. Os sintomas da SOP podem estar associados com a ocorrência de ansiedade, disfunções sexuais e sentimentos de inadequação ao papel feminino, como também podem desencadear sintomas depressivos e isolamento social, com comprometimento significativo da qualidade de vida. Os autores destacam a importância do atendimento multidisciplinar para as mulheres com SOP, considerando essa condição como importante problema psicossocial. A atenção aos aspectos psicossociais da SOP tem aumentado nos últimos anos, no entanto, a produção científica relacionada ainda é escassa

Índices de obesidade central e fatores de risco cardiovascular na síndrome dos ovários policísticos

Fundamento: A obesidade abdominal apresenta elevada prevalência em mulheres com síndrome dos ovários policísticos (SOP) e está associada a um aumento do risco cardiovascular. Objetivo: Verificar a acurácia da circunferência da cintura (CC), da relação cintura-quadril (RCQ), da relação cinturaestatura (RCEST) e do índice de conicidade (índice C), no que se refere à detecção de fatores de risco cardiovascular (FRCV) em mulheres com SOP. Métodos: Por meio de estudo transversal, foram alocadas 102 mulheres (26,5 ± 5 anos) com diagnóstico de SOP, de acordo com o consenso de Rotterdam. O colesterol total (CT), os triglicerídeos (TG), o LDL-colesterol (LDL-C), o HDLcolesterol (HDL-C), a glicemia de jejum, a glicemia após teste oral de tolerância à glicose (TOTG) e a pressão arterial (PA) foram avaliados em todas as pacientes, além das variáveis antropométricas. Resultados: A relação cintura-estatura foi o marcador que apresentou correlações positivas significativas com o maior número de FRCV (PA, TG e glicemia após TOTG), destacando-se ainda a correlação negativa com HDL-C. Todos os marcadores antropométricos avaliados se correlacionaram positivamente com PA, enquanto CC e RCQ apresentaram correlação positiva também com TG. No tocante à acurácia para detecção de FRCV, os indicadores antropométricos considerados apresentaram taxas de sensibilidade superiores a 60%, com destaque para a RCEST, que apresentou sensibilidade superior a 70%. Conclusão: A RCEST demonstrou ser o indicador antropométrico com a melhor acurácia para a predição de FRCV. Nesse sentido, propõe-se a inclusão desse parâmetro de fácil mensuração na avaliação clínica para o rastreamento de mulheres com SOP e FRCV----------------------ABSTRACT Background: Women with polycystic ovary syndrome (PCOS) present a high prevalence of abdominal obesity, which is associated with an increased cardiovascular risk. Objective: To verify the accuracy of the waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR) and the conicity index (CI) in the detection of cardiovascular risk factors (CVRF) in women with PCOS. Methods: The present transversal study allocated 102 women (26.5 ± 5 years) with a diagnosis of PCOS, according to the Rotterdam criteria. Total cholesterol (TC), triglycerides (TG), LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C), fasting glucose, glucose after the oral glucose tolerance test (OGTT) and blood pressure (BP) were evaluated in all patients, in addition to the anthropometric variables. Results: The WHtR was the marker that presented significant positive correlations with the highest number of CVRF (BP, TG and post-OGTT glucose), whereas there was a negative correlation with HDL-C. All the evaluated anthropometric markers were positively correlated with BP, whereas WC and WHR also presented a positive correlation with TG. Regarding the accuracy for the detection of CVRF, the anthropometric markers presented a sensibility > 60%, especially the WHtR, which had a sensibility > 70%. Conclusion: The WHtR showed to be the most accurate anthropometric indicator for the prediction of CVRF. In this sense, we propose the inclusion of this easily-measured parameter in the clinical assessment for the screening of women with PCOS and CVRF

Irregularidade do ciclo menstrual no Menacme como marcador para fatores de risco cardiovasculares na pós-menopausa

A associação entre fatores de risco cardiovascular (FRCV) na pósmenopausa e o antecedente de irregularidade menstrual no menacme foi avaliado em estudo caso-controle envolvendo 414 mulheres na pósmenopausa com idade de 60,4 ± 5,5 anos e IMC de 25,3 ± 4,7 kg/m2. As variáveis consideradas foram: caracterização do ciclo menstrual entre 20 e 35 anos (independente) e relato atual sobre ocorrência de hipertensão arterial, dislipidemia, diabetes mellitus e doença arterial coronariana (dependentes). Utilizou-se o teste qui-quadrado e modelos de regressão logística, ajustados para outras variáveis implicadas no risco para doenças CV, com nível de significância 5%. Observou-se que mulheres que relataram irregularidade menstrual prévia estiveram associadas com risco aumentado para ocorrência de algum FRCV [odds ratio ajustado (OR)= 2,14; IC-95%= 1,02–4,48], quando comparadas àquelas com ciclos regulares. Análise estratificada demonstrou as seguintes associações significativas com o antecedente de irregularidade menstrual: hipertensão arterial (OR= 2,4; 95% IC= 1,39–5,41), hipercolesterolemia (OR= 2,32; 95% IC= 1,17–4,59), hipertrigliceridemia (OR= 2,09; 95% IC= 1,10–4,33) e angioplastia coronariana (OR= 6,82; 95% IC= 1,44–32,18). Os dados sugerem que o antecedente de irregularidade menstrual, indicativo da ocorrência da síndrome dos ovários policísticos na idade reprodutiva, pode estar relacionado com aumento do risco para doenças CV na pós-menopausa __________________________________________________ABSTRACT Menstrual Cycle Irregularity as a Marker of Cardiovascular Risk Factors at Postmenopausal Years.To evaluate the association between cardiovascular risk factors (CVRF)during postmenopausal years and previous menstrual irregularity during reproductive years, we performed a case-control study in 414 postmenopausal women (mean age 60.4 ± 5.5 years; BMI 25.3 ± 4.7 kg/m2). The variables assessed were: menstrual cycle characteristics at age 20–35y (independent) and records of arterial hypertension, dyslipidemia, diabetes mellitus, and coronary heart disease (dependent). Statistical analysis used the chi-square test and logistic regression, adjusting for potential confounders for cardiovascular risk, with significance set at 5%. Women reporting previous menstrual irregularity were associated with increased risk for some CVRF [adjusted odds ratio (OR) 2.14; CI-95%= 1.02–4.48], when compared with those reporting regular menstrual cycles. Stratified analysis demonstrated significant associations of previous menstrual irregularity with: arterial hypertension [OR= 2.74; CI-95%= 1.39–5.41), hypercholesterolemia (OR= 2.32; CI-95%= 1.17–4.59), hypertriglyceridemia (OR= 2.09; CI-95%=1.10–4.33), and coronary angioplasty (OR= 6.82; CI-95%= 1.44–32.18). These data suggest that a prior history of menstrual irregularity, as indicative of polycystic ovary syndrome, may be related to increased risk for CVD during postmenopausal years