Menopausa, estrogênios e disfunção endotelial: aspectos atuais

Menopause is defined as the permanent cessation of menses. Cardiovascular disease is the leading cause of death among postmenopausal women in developed countries. The disparity between the incidence of cardiovascular disease among women in pre- and postmenopause has been ascribed to the actions of endogenous estrogen on the cardiovascular system and, particularly, on the vascular endothelium. The endothelium plays an important role in cardiovascular homeostasis, either through the vascular tonus and its regulation, or through coagulation and the inflammatory response. Endothelial dysfunction is implicated in the genesis of atherosclerosis and other chronic disorders, such as diabetes mellitus and hypertension. The pharmacological use of estrogen exerts influence on the circulating levels of markers of vascular tonus, and inflammation, as well as prothrombotic, and fibrinolytic markers, but the impact of these changes on the atherosclerotic disease is still uncertain.A menopausa é definida como a cessação permanente das menstruações. A doença cardiovascular é a principal causa de mortalidade em mulheres na pós- menopausa, em países desenvolvidos. A disparidade entre a incidência de doença cardiovascular entre mulheres na pré e pós menopausa tem sido atribuída a ações do estrogênio endógeno sobre o sistema cardiovascular e, em especial, sobre a função do endotélio vascular. O endotélio tem importante papel na homestase cardiovascular, seja no controle do tônus e permeabilidade vascular, ou da coagulação e resposta inflamatória. A disfunção endotelial está implicada na gênese da aterosclerose e de outras doenças crônicas, como diabete melito e hipertensão arterial. O uso farmacológico de estrogênio exerce influência sobre concentrações circulantes de marcadores do tônus vascular, inflamatórios, pró-trombóticos e fibrinolíticos, porém o impacto destas alterações sobre a doença aterosclerótica ainda não está determinado

Association between hyperinsulinemia and endogenous androgen levels in peri and postmenopausal women

We evaluated the relationship between hyperinsulinemia and anthropometric, metabolic, and hormonal parameters that might contribute to risk for coronary heart disease in 104 peri and postmenopausal women. Plasma glucose, insulin, LH, FSH, sex hormone binding globulin (SHBG), and total testosterone (TT) were determined. Free androgen index (FAI) and fasting insulin to glucose ratio (IGR) were calculated. The cut-off point to define hyperinsulinemia was established at 23 mIU/mg. Mean age was 54.8 years. Mean age at menopause was 47.7 years. Body mass index (BMI) was >25 in 46 patients, and 28 (26.9%) were hyperinsulinemic. BMI, waist circumference, triglycerides, and 2-hour post-glucose insulin levels were significantly higher in hyperinsulinemic patients. Hyperinsulinemic patients had higher TT levels (p=0.02), FAI (p=0.0001), and lower SHBG levels (p=0.003). Positive correlations were observed between IGR and BMI, waist to hip ratio, waist circumference, and triglycerides. IGR and HDL-C were negatively correlated. IGR presented a positive association with TT and FAI, and a negative association with SHBG. FAI contributed positively to IGR, independently of BMI, age, or time since menopause. In conclusion, androgen levels may be important determinants of cardiovascular risk in peri and postmenopausal women. However, this observation should be confirmed by longitudinal studies

ASSOCIAÇÃO ENTRE HIPERINSULINEMIA E NÍVEIS DE ANDROGÊNIOS ENDÓGENOS EM MULHERES NA PERI E PÓS-MENOPAUSA

We evaluated the relationship between hyperinsulinemia and anthropometric, metabolic, and hormonal parameters that might contribute to risk for coronary heart disease in 104 peri and postmenopausal women. Plasma glucose, insulin, LH, FSH, sex hormone binding globulin (SHBG), and total testosterone (TT) were determined. Free androgen index (FAI) and fasting insulin to glucose ratio (IGR) were calculated. The cut-off point to define hyperinsulinemia was established at 23 mIU/mg. Mean age was 54.8 years. Mean age at menopause was 47.7 years. Body mass index (BMI) was >25 in 46 patients, and 28 (26.9%) were hyperinsulinemic.BMI, waist circumference, triglycerides, and 2-hour post-glucose insulin levels were significantly higher in hyperinsulinemic patients. Hyperinsulinemic patients had higher TT levels (p=0.02), FAI (p=0.0001), and lower SHBG levels (p=0.003). Positive correlations were observed between IGR and BMI, waist to hip ratio, waist circumference, and triglycerides. IGR and HDL-C were negatively correlated. IGR presented a positive association with TT and FAI, and a negative association with SHBG. FAI contributed positively to IGR, independently of BMI, age, or time since menopause. In conclusion, androgen levels may be important determinants of cardiovascular risk in peri and postmenopausal women. However, this observation should be confirmed by longitudinal studies.We evaluated the relationship between hyperinsulinemia and anthropometric, metabolic, and hormonal parameters that might contribute to risk for coronary heart disease in 104 peri and postmenopausal women. Plasma glucose, insulin, LH, FSH, sex hormone binding globulin (SHBG), and total testosterone (TT) were determined. Free androgen index (FAI) and fasting insulin to glucose ratio (IGR) were calculated. The cut-off point to define hyperinsulinemia was established at 23 mIU/mg. Mean age was 54.8 years. Mean age at menopause was 47.7 years. Body mass index (BMI) was >25 in 46 patients, and 28 (26.9%) were hyperinsulinemic.BMI, waist circumference, triglycerides, and 2-hour post-glucose insulin levels were significantly higher in hyperinsulinemic patients. Hyperinsulinemic patients had higher TT levels (p=0.02), FAI (p=0.0001), and lower SHBG levels (p=0.003). Positive correlations were observed between IGR and BMI, waist to hip ratio, waist circumference, and triglycerides. IGR and HDL-C were negatively correlated. IGR presented a positive association with TT and FAI, and a negative association with SHBG. FAI contributed positively to IGR, independently of BMI, age, or time since menopause. In conclusion, androgen levels may be important determinants of cardiovascular risk in peri and postmenopausal women. However, this observation should be confirmed by longitudinal studies

Associations between body composition and lifestyle factors with bone mineral density according to time since menopause in women from Southern Brazil : a cross-sectional study

Background: The aim of this study was to investigate whether body composition, dietary pattern and habitual physical activity are associated with BMD according to time since menopause in women from Southern Brazil with no clinical evidence of disease. Methods: 99 participants were enrolled and anthropometry, body composition and BMD by dual energy x-ray absorptiometry, rest metabolic rate by indirect calorimetry, dietary pattern by semi quantitative food frequency questionnaire and habitual physical activity by pedometer were performed. Results: Mean age was 55.2 ± 4.9 years and mean time since menopause was 6.8 ± 1.0 years. Weight, BMI, lean and fat mass and RMR were higher in women with less than 5 years since menopause with normal versus low bone mass. No differences were found in the studied variables between participants with normal or low bone mass and more than 5 years of menopause. Women with > 5 years since menopause had higher prevalence of osteoporosis, as well as lower BMD in all sites when compared to those with less time since menopause. Calories, carbohydrate, protein, fat and micronutrients intake were similar between groups. When the sample was adjusted for time since menopause, the odds ratio (OR) for low bone mass was 5.21 (95 % CI 1.57–17.25, P = 0.004) for BMI <25 kg/m², for lean mass <37.5 Kg an OR of 4.4 (95 % CI 1.64–11.80, P = 0.004, for fat mass <26.0 Kg an OR of 3.39 (95 % CI 1.29–8.85, P = 0.010) and for the intake of vitamin A < 700 mcg/day an OR of 3.00 (95 % CI 1.13–7.94, P = 0.012). Low meat and eggs intake or low protein intake did not influence the odds ratio for low bone mass. Conclusion: In this cross-sectional study with postmenopausal women with no clinical evidence of disease, time since menopause, low lean and fat mass were associated with low bone mass. Calories and macronutrients intake as well as habitual physical activity did not interfere with BMD, but participants were mostly sedentary. Further studies are needed in order to determine whether the adequate intake of specific food groups and the type of physical activity could attenuate the time since menopause impact on BMD

Association between global leukocyte DNA methylation and cardiovascular risk in postmenopausal women

BACKGROUND: Genetic studies to date have not provided satisfactory evidence regarding risk polymorphisms for cardiovascular disease (CVD). Conversely, epigenetic mechanisms, including DNA methylation, seem to influence the risk of CVD and related conditions. Because postmenopausal women experience an increase in CVD, we set out to determine whether global DNA methylation was associated with cardiovascular risk in this population. METHODS: In this cross sectional study carried out in a university hospital, 90 postmenopausal women without prior CVD diagnosis (55.5 ± 4.9 years, 5.8 [3.0–10.0] years since menopause) were enrolled. DNA was extracted from peripheral leukocytes and global DNA methylation levels were obtained with an ELISA kit. Cardiovascular risk was estimated by the Framingham General Cardiovascular Risk Score (10-year risk) (FRS). Clinical and laboratory variables were assessed. Patients were stratified into two CVD risk groups: low (FRS: <10 %, n = 69) and intermediate/high risk (FRS ≥10 %, n = 21). RESULTS: Age, time since menopause, blood pressure, total cholesterol, and LDL-c levels were higher in FRS ≥10 % group vs. FRS <10 % group. BMI, triglycerides, HDL-c, HOMA-IR, glucose and hsC-reactive protein levels were similar in the two groups. Global DNA methylation (% 5mC) in the overall sample was 26.5 % (23.6–36.9). The FRS ≥10 % group presented lower global methylation levels compared with the FRS <10 % group: 23.9 % (20.6–29.1) vs. 28.8 % (24.3–39.6), p = 0.02. This analysis remained significant even after adjustment for time since menopause (p = 0.02). CONCLUSIONS: Our results indicate that lower global DNA methylation is associated with higher cardiovascular risk in postmenopausal women

Avaliação da função endotelial e associação com androgênios endógenos em pacientes pós-menopáusicas

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ASSOCIAÇÃO ENTRE HIPERINSULINEMIA E NÍVEIS DE ANDROGÊNIOS ENDÓGENOS EM MULHERES NA PERI E PÓS-MENOPAUSA

We evaluated the relationship between hyperinsulinemia and anthropometric, metabolic, and hormonal parameters that might contribute to risk for coronary heart disease in 104 peri and postmenopausal women. Plasma glucose, insulin, LH, FSH, sex hormone binding globulin (SHBG), and total testosterone (TT) were determined. Free androgen index (FAI) and fasting insulin to glucose ratio (IGR) were calculated. The cut-off point to define hyperinsulinemia was established at 23 mIU/mg. Mean age was 54.8 years. Mean age at menopause was 47.7 years. Body mass index (BMI) was &gt;25 in 46 patients, and 28 (26.9%) were hyperinsulinemic.BMI, waist circumference, triglycerides, and 2-hour post-glucose insulin levels were significantly higher in hyperinsulinemic patients. Hyperinsulinemic patients had higher TT levels (p=0.02), FAI (p=0.0001), and lower SHBG levels (p=0.003). Positive correlations were observed between IGR and BMI, waist to hip ratio, waist circumference, and triglycerides. IGR and HDL-C were negatively correlated. IGR presented a positive association with TT and FAI, and a negative association with SHBG. FAI contributed positively to IGR, independently of BMI, age, or time since menopause. In conclusion, androgen levels may be important determinants of cardiovascular risk in peri and postmenopausal women. However, this observation should be confirmed by longitudinal studies.We evaluated the relationship between hyperinsulinemia and anthropometric, metabolic, and hormonal parameters that might contribute to risk for coronary heart disease in 104 peri and postmenopausal women. Plasma glucose, insulin, LH, FSH, sex hormone binding globulin (SHBG), and total testosterone (TT) were determined. Free androgen index (FAI) and fasting insulin to glucose ratio (IGR) were calculated. The cut-off point to define hyperinsulinemia was established at 23 mIU/mg. Mean age was 54.8 years. Mean age at menopause was 47.7 years. Body mass index (BMI) was &gt;25 in 46 patients, and 28 (26.9%) were hyperinsulinemic.BMI, waist circumference, triglycerides, and 2-hour post-glucose insulin levels were significantly higher in hyperinsulinemic patients. Hyperinsulinemic patients had higher TT levels (p=0.02), FAI (p=0.0001), and lower SHBG levels (p=0.003). Positive correlations were observed between IGR and BMI, waist to hip ratio, waist circumference, and triglycerides. IGR and HDL-C were negatively correlated. IGR presented a positive association with TT and FAI, and a negative association with SHBG. FAI contributed positively to IGR, independently of BMI, age, or time since menopause. In conclusion, androgen levels may be important determinants of cardiovascular risk in peri and postmenopausal women. However, this observation should be confirmed by longitudinal studies

Association between hyperinsulinemia and endogenous androgen levels in peri and postmenopausal women

We evaluated the relationship between hyperinsulinemia and anthropometric, metabolic, and hormonal parameters that might contribute to risk for coronary heart disease in 104 peri and postmenopausal women. Plasma glucose, insulin, LH, FSH, sex hormone binding globulin (SHBG), and total testosterone (TT) were determined. Free androgen index (FAI) and fasting insulin to glucose ratio (IGR) were calculated. The cut-off point to define hyperinsulinemia was established at 23 mIU/mg. Mean age was 54.8 years. Mean age at menopause was 47.7 years. Body mass index (BMI) was >25 in 46 patients, and 28 (26.9%) were hyperinsulinemic. BMI, waist circumference, triglycerides, and 2-hour post-glucose insulin levels were significantly higher in hyperinsulinemic patients. Hyperinsulinemic patients had higher TT levels (p=0.02), FAI (p=0.0001), and lower SHBG levels (p=0.003). Positive correlations were observed between IGR and BMI, waist to hip ratio, waist circumference, and triglycerides. IGR and HDL-C were negatively correlated. IGR presented a positive association with TT and FAI, and a negative association with SHBG. FAI contributed positively to IGR, independently of BMI, age, or time since menopause. In conclusion, androgen levels may be important determinants of cardiovascular risk in peri and postmenopausal women. However, this observation should be confirmed by longitudinal studies