Effects of estradiol alone and combined with norethisterone acetate on pulse-wave velocity in hypertensive postmenopausal women.

BACKGROUND: Arterial hypertension and postmenopausal reduction of estrogen levels may be involved in modifications of the stiffness of large arteries. OBJECTIVES: To evaluate the pulse-wave velocity (PWV) and indirectly the arterial stiffness in hypertensive postmenopausal women submitted to hormone therapy with estradiol alone or combined with norethisterone acetate. SUBJECTS: Forty-five hypertensive postmenopausal women were double-blindly, randomly assigned to three arms of treatment: placebo (group I); estradiol 2 mg/day (group II); or estradiol 2 mg/day and norethisterone acetate 1 mg/day (group III). METHODS: Arterial stiffness was assessed from PWV measurements of the common carotid and femoral arteries (CF-PWV) and the common carotid and radial arteries (CR-PWV) obtained using the automatic Complior(R) device, taken at baseline and after 12 weeks of treatment. RESULTS: After the 12-week treatment, values of CF-PWV and CR-PWV were not significantly different (p = 0.910 and p = 0.736, respectively) among the groups. Systolic blood pressure showed a positive correlation with CF-PWV in groups II and III (p = 0.02 and p < 0.001, respectively). CONCLUSIONS: PWV and arterial stiffness in postmenopausal hypertensive women did not reduce over a 12-week treatment with estradiol alone compared with the same period of treatment with estradiol combined with norethisterone acetate.

Systemic sclerosis and bone loss: the role of the disease and body composition.

OBJECTIVES: Studies on body composition are not available in systemic sclerosis (SSc). As this variable may play an important role in bone loss we have analysed bone mineral density (BMD) and body composition in SSc patients and healthy controls. METHODS: Forty-three postmenopausal SSc patients and 47 healthy postmenopausal women were studied. Patients with intestinal malabsorption, renal failure, current or past history of smoking or using osteopenic drugs were excluded. BMD and body composition was evaluated by dual X-ray absorptiometry (DXA). RESULTS: A higher frequency of osteoporosis in the lumbar spine (32.5%) and femoral neck (51.1%) was observed in SSc patients when compared to controls (14.8% vs. 19.1%; p<0.01). Multiple linear regression analysis revealed an association between the presence of SSc and low BMD. Body composition showed a reduced lean mass (33.15 vs. 39.99 g; p<0.01) and fat mass (21.05 vs. 26.82 g; p<0.01) in SSc when compared to controls. Lean mass was an important factor related to BMD in the lumbar spine and femoral neck. CONCLUSION: SSc may be an independent factor for low BMD. The low lean mass in these patients emphasizes the need for appropriate additional therapeutic measures to reduce bone loss in SSc patients.

Effect of sexual steroids on the calcium content of aortic atherosclerotic plaque of oophorectomized rabbits.

We determined the effect of conjugated equine estrogen plus medroxyprogesterone acetate on calcium content of aortic atherosclerotic lesions in oophorectomized adult New Zealand rabbits submitted to a cholesterol rich diet. Five groups of 10 animals each were studied: G1 = control, G2 = cholesterol diet only, G3 = diet plus conjugated equine estrogen (0.625 mg/day); G4 and G5 = diet, conjugated equine estrogen (0.625 mg/day) plus medroxyprogesterone acetate (5 and 10 mg/day, respectively). Mean weight varied from 2.7 +/- 0.27 to 3.1 +/- 0.20 kg (P = 0.38) between groups at the beginning and 3.1 +/- 0.27 to 3.5 +/- 0.20 kg (P = 0.35) at the end of the experiment. Cholesterol and triglyceride levels were determined at the time of oophorectomy, 21 days after surgery (time 0), and at the end of follow-up of 90 days. The planimetric method was used to measure plaque and caryometric method for histopathologic examination of the aorta. Calcium content was determined by the method of von Kossa. A similar increase in cholesterol occurred in all treated groups without differences between them at the end of the study. Groups G4 and G5 had smaller areas of atherosclerotic lesions (2.33 +/- 2.8 and 2.45 +/- 2.1 cm(2), respectively) than the groups receiving no progestogens (G2: 5.6 +/- 4 and G3: 4.6 +/- 2.8 cm(2); P = 0.02). The relation between lesion area and total aorta area was smaller in groups treated with combined drugs compared to the groups receiving no progesterone (G4: 14.9 +/- 13 and G5: 14.2 +/- 13.4 vs G2: 35.8 +/- 26 and G3: 25 +/- 8 cm(2), respectively; P = 0.017). Oral conjugated equine estrogen (0.625 mg/day) plus medroxyprogesterone acetate (5 or 10 mg/day) provoked a greater reduction in atherosclerotic plaque area and calcium content in treated groups, suggesting a dose-dependent effect.

Effect of sexual steroids on the calcium content of aortic atherosclerotic plaque of oophorectomized rabbits

We determined the effect of conjugated equine estrogen plus medroxyprogesterone acetate on calcium content of aortic atherosclerotic lesions in oophorectomized adult New Zealand rabbits submitted to a cholesterol rich diet. Five groups of 10 animals each were studied: G1 = control, G2 = cholesterol diet only, G3 = diet plus conjugated equine estrogen (0.625 mg/day); G4 and G5 = diet, conjugated equine estrogen (0.625 mg/day) plus medroxyprogesterone acetate (5 and 10 mg/day, respectively). Mean weight varied from 2.7 ± 0.27 to 3.1 ± 0.20 kg (P = 0.38) between groups at the beginning and 3.1 ± 0.27 to 3.5 ± 0.20 kg (P = 0.35) at the end of the experiment. Cholesterol and triglyceride levels were determined at the time of oophorectomy, 21 days after surgery (time 0), and at the end of follow-up of 90 days. The planimetric method was used to measure plaque and caryometric method for histopathologic examination of the aorta. Calcium content was determined by the method of von Kossa. A similar increase in cholesterol occurred in all treated groups without differences between them at the end of the study. Groups G4 and G5 had smaller areas of atherosclerotic lesions (2.33 ± 2.8 and 2.45 ± 2.1 cm², respectively) than the groups receiving no progestogens (G2: 5.6 ± 4 and G3: 4.6 ± 2.8 cm²; P = 0.02). The relation between lesion area and total aorta area was smaller in groups treated with combined drugs compared to the groups receiving no progesterone (G4: 14.9 ± 13 and G5: 14.2 ± 13.4 vs G2: 35.8 ± 26 and G3: 25 ± 8 cm², respectively; P = 0.017). Oral conjugated equine estrogen (0.625 mg/day) plus medroxyprogesterone acetate (5 or 10 mg/day) provoked a greater reduction in atherosclerotic plaque area and calcium content in treated groups, suggesting a dose-dependent effect.

A prospective open-label study to evaluate the effects of the oral contraceptive Harmonet (gestodene75/EE20) on body fat.

This open-label study evaluated the effects on body fat of the use of a low-dose oral contraceptive (gestodene75/EE20) in a group of 61 women (OC-U group) as compared to a nonuser group (OC-N group) of 51 women who did not receive an oral contraceptive. Weight, body mass index (BMI), waist-over-hip ratio and body composition data, obtained by bioelectrical impedance [percentages of body fat (%FAT), water (%TBW) and lean mass (%FFM)], were assessed before and after six treatment cycles. Baseline OC-U group weight, BMI, %FAT, %TBW and %FFM did not differ from the OC-N group, either at baseline or at the end of the study, and did not significantly change within each group during the study. Also, there was no modification of fat distribution in either group. Among women in the OC-U group, there was a slight increase in total cholesterol levels and a trend towards higher triglycerides levels. No changes were detected in blood pressure. In conclusion, this low-dose oral contraceptive did not affect weight or body composition. Thus, our data suggest that gestodene75/EE20 represents an appropriate OC choice and may enhance compliance of women who mistakenly believe that the use of oral contraceptives always leads to weight gain.

Acute and chronic effects of oestradiol on left ventricular diastolic function in hypertensive postmenopausal women with left ventricular diastolic dysfunction.

BACKGROUND: Left ventricular function changes in the postmenopausal state. However, there are conflicting reports about the effects of oestrogen on left ventricular diastolic function in postmenopausal women. OBJECTIVE: To evaluate the acute and chronic effects of oestradiol in physiological doses on diastolic heart function in hypertensive postmenopausal women with left ventricular diastolic dysfunction. METHODS: A prospective, randomised, double blind, placebo controlled study was used to evaluate the effects of oestradiol in 34 hypertensive women with left ventricular dysfunction. The acute effects of a single 1 mg oral dose of oestradiol or placebo were determined after 90 minutes. The chronic effects of 1 mg oestradiol orally/day or placebo were determined after 12 weeks. Diastolic functional indices (mitral flow and pulmonary venous flow) were assessed by Doppler echocardiography. RESULTS: Though an appropriate serum concentration was achieved, no acute effect of oestradiol administration on left ventricular diastolic function was identified. After 12 weeks of treatment the following changes (mean (SD)) were identified in the oestradiol group: a decrease in isovolumic relaxation time from 127 (23) to 106 (16) ms (p < 0.001), and in the deceleration time of the mitral E wave from 260 (42) to 238 (20) ms (p < 0.05); and an increase in the E/A ratio from 0.8 (0.2) (basal) to 1.0 (0.2) after 12 weeks (p < 0.001). CONCLUSIONS: Hypertensive postmenopausal women who had hormone replacement therapy over a period of 12 weeks had significant improvement in left ventricular diastolic function. No changes were identified following acute administration.

Effects of estradiol on myocardial global performance index in hypertensive postmenopausal women.

The objective of this study was to assess the acute and chronic effects of estradiol on the myocardial performance index (MPI) in hypertensive postmenopausal women. There are conflicting reports on the effects of estrogen on left ventricular function in postmenopausal women, and we are unaware of any study on the myocardial performance index in the postmenopausal state. We undertook a prospective, randomized, double-blind, placebo-controlled study in 34 women, distributed into an estradiol group or a placebo group. After 90 min and at 12 weeks of administration of 1 mg of oral estradiol we evaluated, by Doppler echocardiography, its effects on the MPI. The estradiol group showed no alteration in the MPI after 90 min of the administration of estradiol. On the other hand, after 12 weeks of treatment we observed a statistically significant decrease of isovolumic relaxation time, from 127+/-23 ms to 106+/-16 ms (p < 0.001 and of the MPI from 0.63+/-0.13 to 0.48+/-0.09 (p < 0.01) and an increase in ejection time, from 297+/-32 ms to 330+/-31 ms (p < 0.01). In conclusion, estrogen replacement therapy over a period of 12 weeks showed a significant improvement in the MPI in hypertensive postmenopausal women, whereas the acute administration did not have any effect.

Histological classification of endometriosis as a predictor of response to treatment.

OBJECTIVES: To evaluate the usefulness of the histological classification of endometriosis in predicting responses to treatment. METHODS: We evaluated 412 biopsy specimens from 241 patients with pelvic endometriosis. Pain and infertility were evaluated before surgery. Disease location and stage of development were analyzed according to the 1985 American Society of Reproductive Medicine (ASRM) classification. Histological findings were classified as stromal, well-differentiated, undifferentiated, and mixed endometriosis. Clinical response to pain or infertility was evaluated. RESULTS: Histological findings, disease location and stage of development, and response to treatment were compared. Undifferentiated endometriosis was more frequently associated with stages III/IV than the well-differentiated and stromal histological types. Pure or mixed undifferentiated patterns were more frequently associated with rectovaginal endometriosis. When considering pain symptoms, patients presenting well-differentiated or stromal histological patterns responded better to therapeutic treatment than those who presented undifferentiated histological patterns. There were no significant differences in cases related to sterility. CONCLUSIONS: The histological categorization of endometriosis can help predict the behavioral patterns of the disease.

Clustering of traditional risk factors and precocity of coronary disease in women.

BACKGROUND: Women usually develop coronary artery disease (CAD) 10 years later than men do. CAD in women is associated with menopausal status and the number and intensity of risk factors. But, when the age gap between men and women narrows, less is known about the influence of risk factors on CAD. METHODS: We assessed the prevalence of traditional risk factors in 850 men and 468 women with stable CAD who had mean age, 58.3+/-8.6 and 58.8+/-10.3 years (P=NS), respectively. RESULTS: Univariate analysis of risk factors showed that body mass index (BMI), hypertension (all three stages), diabetes, triglycerides (> or =2.8 mmol/l), cholesterol (> or =6.2 mmol/l) and family history were more prevalent in women. Smoking and previous myocardial infarction (MI) were more prevalent in men. Multivariable analysis disclosed hypertension, diabetes, dyslipidemia and family history as independent risk factors for women with stable CAD and smoking and previous MI as independent risk factors for men. CONCLUSION: Clustering of traditional risk factors may explain the precocity of CAD in women who are near in age to men.

A mulher coronariopata no climatério após a menopausa: implicaçöes na qualidade de vida / The post menopausal climacteric woman with coronary artery disease: implications to quality of life

OBJETIVOS: Avaliar a qualidade de vida em mulheres com doença isquêmica do coraçäo no climatério após a menopausa. MÉTODOS: O estudo incluiu 100 mulheres após a menopausa, sendo 50 portadoras de doença arterial coronária (DAC) em seguimento no Instituto do Coraçäo (InCor) HC-FMUSP e 50 que näo apresentavam doenças associadas (grupo controle) atendidas no Centro de Saúde Escola Geraldo de Paula Souza da FSP - USP. A qualidade de vida foi avaliada mediante a utilizaçäo de dois instrumentos: uma entrevista estruturada e a aplicaçäo do questionário genérico de avaliaçäo de qualidade de vida ( SF - 36 ). RESULTADOS: Os grupos eram homogêneos em relaçäo à idade da última menstruaçäo: 49 ±3,9 anos na DAC e 49,2±3 anos no grupo controle. Os grupos também eram similares quanto à escolaridade: 84 por cento possuíam primeiro grau (completo ou incompleto); estado civil: casadas 64 por cento das DAC e 45 por cento do grupo controle e viúvas 18 por cento da DAC e 24 por cento das controle. A atividade profissional fora do lar foi significativamente mais freqüente no grupo controle (52 por cento) e 14 por cento nas DAC (p=0,0001). Ambos os grupos demonstraram percepçöes semelhantes no que se refere à sexualidade. A avaliaçäo da qualidade de vida pelo SF - 36 mostrou melhores resultados no grupo controle em relaçäo a: capacidade física (84 vs 50,5 na DAC); aspectos físicos (84 vs 45,5); estado geral de saúde (87,2 vs 59,1); vitalidade (69,7 vs 51,4) e escore total dos componentes mentais (70,4 vs 58,6). CONCLUSÄO: A coronariopatia interfere na qualidade de vida das mulheres após a menopausa, limitando a capacidade física e o desempenho das atividades da vida diária, além de intensificar as dificuldades emocionais desse período

Triglyceride and lipoprotein (a) are markers of coronary artery disease severity among postmenopausal women.

OBJECTIVE: After menopause, some women manifest coronary artery disease (CAD) with highly variable angiographic severity. For these women, postmenopausal appearing of some CAD risk factors may have differently influenced the CAD risk and severity. In this study, we attempt to unravel differences in the frequency or intensity of CAD risk factors among postmenopausal women with different angiographic severity. METHODS: We studied 182 postmenopausal women (64+/-6 years) who underwent coronary angiography to investigate thoracic pain. Subjects with no detectable coronary lesions at angiography were recruited to the non-obstructive group and patients with CAD were grouped in one-vessel or multi-vessel groups. We compared clinical variables as the body mass index (BMI), age at menopause, age, hypertension, diabetes and cigarette smoking, and lipid measurements as plasma levels of total cholesterol, triglyceride, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, apolipoprotein (apo) A1, apo B and lipoprotein(a) (Lp(a)). RESULTS: Comparing to the non-obstructive group, Lp(a) was twofold higher in the one-vessel group and threefold higher in the multi-vessel group and triglycerides were 34% higher in the one-vessel group and 50% higher in the multi-vessel group. No further difference was found among the three groups. After multivariate logistic regression analysis, triglyceride (odds ratio: 1.01; P=0.0013) and Lp(a) (odds ratio: 1.006; P<0.0001) were independently indicative of the presence of obstructive CAD. CONCLUSIONS: We found that both Lp(a) and triglycerides constitute useful markers of CAD severity among postmenopausal women.

Trends in death from circulatory diseases in Brazil between 1979 and 1996.

OBJECTIVE: To analyze the trends in mortality due to circulatory diseases in men and women aged > or =30 years in Brazil from 1979 to 1996. METHODS: We analyzed population count data obtained from the IBGE Foundation and mortality data obtained from the System of Information on Mortality of the DATASUS of the Ministry of Health. RESULTS: Circulatory diseases, ischemic heart disease, and cerebrovascular disease were the major causes of death in men and women in Brazil. The standardized age coefficient for circulatory disease in men aged > or =30 years ranged from 620 to 506 deaths/100,000 inhabitants and in women from 483 to 383 deaths/100,000 inhabitants for the years 1979 and 1996, respectively. In men, the mean coefficient for the period was 586.25 deaths with a significant trend towards a decrease (P<0.001) and a decline of 8.25 deaths/year. In women, the mean coefficient for the period was 439.58 deaths, a significant trend towards a decrease (P<0.001) and a rate of decline of 7.53 deaths/year. The same significant trend towards a decrease in death (P<0.001) was observed for ischemic heart disease and cerebrovascular disease. Risk of death from these causes was always higher for men of any age group (P<0.001). Cerebrovascular disease was the primary cause of death in women. CONCLUSION: Although circulatory diseases have been the major cause of mortality in men and women in the Brazilian population, with a greater participation by cerebrovascular diseases, a trend towards a decrease in the risk of death from these causes is being observed.

[The post menopausal climacteric woman with coronary artery disease: implications to quality of life]. / A mulher coronariopata no climatério após a menopausa: implicações na qualidade de vida.

PURPOSE: To analyse the quality of life of post menopausal women with coronary artery disease. METHODS: The population consisted of 100 women, divided into 2 groups. The first group made up of 50 women whose average age was 58 +/- 4,2 years with > stable coronary artery disease (CAD) proved by angiography undergoing treatment at The Heart Institute (InCor) - University of São Paulo Medical School, Brazil (CAD group). This group was compared with 50 women (55.1 +/- 5.4 years old) without clinical evidence of coronary artery disease (control group) from a primary health care center, Centro de Saúde Escola Geraldo de Paula Souza, São Paulo - FSP- USP. The quality of life was assessed by a structured interview and by Medical outcomes study 36-item short-form health survey (SF-36) validated to the Brazilian population. RESULTS: They were homogenous regarding age of the last menstruation period: 49 +/- 3.9 years old in CAD and 49.2 +/- 3 years old in controls. The groups were also similar in education level, marital status (64% of CAD and 45% of controls were married; and 18% of CAD and 24% of controls were widowhood). The active working status was more frequent in controls than in CAD (52% vs. 14%; p= 0.0001). Both groups showed similar perceptions in their sexual experience. The evaluation of quality of life by SF-36 showed better scores for the control group in: physical functioning (84 vs. 50.5), role physical (84 vs. 45,5), general health (87.2 vs. 59.1), vitality (69.7 vs. 51,4), p<0.0001; and total score of mental components (70.4 vs. 58.6), p = 0.028. CONCLUSION: Coronary artery disease alters the quality of life of climacteric women by limiting the physical capacity to perform ordinary daily activities and by intensifying emotional conflicts usually present in this phase of life.