Association Between Hormone Therapy and Weight Gain in the Menopause Transition and After Menopause: A Systematic Review and Meta-Analysis

Objectives: to conduct a systematic review and meta-analysis in order to assess whether hormone therapy (HT) increases weight in women in the menopausal transition and after menopause. Method: this article proposes an update to the systematic review published in 2005 by the Cochrane Library (Kongnyuy EJ et al 2005) with reference to studies assessing weight changes in women receiving HT from 1986 to 2005. Following PRISMA recommendations, we included randomized controlled trials (RCTs) ) from May 2005 onwards from Medline, Embase, and the Cochrane CENTRAL databases. Standardized mean differences (SMD) and 95% confidence intervals (CI) were calculated. Two authors independently assessed the risk of biases in the selected studies. Results: ten RCTs were included, totaling 2,588 HT users and 764 non-users. Different regimens, dosages, and routes of administration in HT users were analyzed and compared to non-users. The results did not show statistically significant differences for most of the HT regimens evaluated. There was significant weight gain only in patients using EEC alone at dosages of 0.45 mg/day and 0.3 mg/day when compared to placebo (p 0.01); as well as in patients receiving esto-progestative combinations of 0.5 mg/day 17-beta-estradiol (E2) + 100 mg/day progesterone, with a 0.7 kg weight increase (p 0.032). On the other hand, the combinations of 1 mg/day estradiol valerate + 3 mg/day drospirenone showed a -1.0 kg reduction (p = 0.04), whereas a -0.2 kg reduction (p = 0.001) was identified in patients using 1 mg /day estradiol (E) + 0.5 mg norethisterone acetate (NETA). Tibolone therapy showed no statistically significant changes in weight. After performing a meta-analysis, the comparative results between users and non-users showed that there was a slight weight increase (+0.279 kg ; CI -1.71 to 2.27) in patients using 0.625 mg/day conjugated equine estrogen (CEE) + 2.5 mg/day medroxyprogesterone acetate (MPA). As for the patients receiving 2.5 mg/day Tibolone, weight gain (+0.670 kg; CI from -1.14 to 2.48) was also observed in them. However, these increases were not significant when compared to non-HT users. Conclusions: most regimens studied showed that patients using HT in the menopausal transition and after menopause did not show significant weight gain. The only combination that showed weight gain was 0.5 mg/day 17-beta-estradiol (E2) + 100 mg/day progesterone observed, while there was weight reduction in patients using 1 mg/day estradiol valerate + 3 mg/day drospirenone and 1 mg/day estradiol (E) + norethisterone acetate.

Objetivo: realizar uma revisão sistemática e meta-análise para avaliar se a terapia hormonal (TH) aumenta o peso em mulheres na transição menopausal e após a menopausa. Métodos: este artigo propõe uma atualização da revisão sistemática publicada em 2005 pela Cochrane Library (Kongnyuy EJ et al., 2005) com referência a estudos avaliando mudanças de peso em mulheres recebendo TH de 1986 a 2005. Seguindo as recomendações do PRISMA, incluímos ensaios clínicos randomizados (RCTs) de maio de 2005 em diante do Medline, Embase e dos bancos de dados Cochrane CENTRAL. Diferenças médias padronizadas (SMD) e intervalos de confiança de 95% (IC) foram calculados. Dois autores avaliaram independentemente o risco de vieses nos estudos selecionados. Resultados: foram incluídos dez ECRs, totalizando 2.588 usuários de HT e 764 não usuários. Diferentes esquemas, dosagens e vias de administração em usuários de HT foram analisados e comparados a não usuários. Os resultados não mostraram diferenças estatisticamente significativas para a maioria dos esquemas de TH avaliados. Houve ganho de peso significativo apenas nos pacientes que usaram apenas EEC nas doses de 0,45 mg/dia e 0,3 mg/dia quando comparados ao placebo (p 0,01); assim como em pacientes recebendo combinações estoprogestativas de 0,5 mg/dia de 17-beta-estradiol (E2) + 100 mg/dia de progesterona, com aumento de peso de 0,7 kg (p 0,032). Por outro lado, as combinações de 1 mg/dia de valerato de estradiol + 3 mg/dia de drospirenona apresentaram redução de -1,0 kg (p = 0,04), enquanto foi identificada redução de -0,2 kg (p = 0,001) nas pacientes que usaram 1 mg /dia estradiol (E) + 0,5 mg de acetato de noretisterona (NETA). A terapia com tibolona não mostrou alterações estatisticamente significativas no peso. Após realizar uma meta-análise, os resultados comparativos entre usuárias e não usuárias mostraram que houve um leve aumento de peso (+0,279 kg ; IC -1,71 a 2,27) em pacientes em uso de 0,625 mg/dia de estrogênio equino conjugado (CEE) + 2,5 mg/dia de acetato de medroxiprogesterona (MPA). Quanto aos pacientes que receberam Tibolona 2,5 mg/dia, também foi observado ganho de peso (+0,670 kg; IC de -1,14 a 2,48). No entanto, esses aumentos não foram significativos quando comparados aos não usuários de HT. Conclusões: a maioria dos esquemas estudados mostrou que as pacientes em uso de TH na transição menopausal e após a menopausa não apresentaram ganho de peso significativo. A única combinação que apresentou ganho de peso foi 0,5 mg/dia de 17-beta-estradiol (E2) + 100 mg/dia de progesterona, enquanto houve redução de peso nas pacientes que usaram 1 mg/dia de valerato de estradiol + 3 mg/dia de drospirenona e 1 mg/dia estradiol (E) + acetato de noretisterona.

Effects of Insulin Resistance on Myocardial Blood Flow and Arterial Peripheral Circulation in Patients with Polycystic Ovary Syndrome.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is associated with increased risk for cardiovascular disease. We sought to evaluate the effects of insulin resistance (IR) on myocardial microcirculation and peripheral artery function in patients with PCOS. METHODS: We studied 55 women (28 with PCOS without IR, 18 with PCOS and IR and 11 normal controls) who underwent laboratorial analysis, high-resolution vascular ultrasound and real time myocardial contrast echocardiography (RTMCE). Intima-media thickness (IMT) and brachial artery flow-mediated dilation (FMD) were evaluated by vascular ultrasound. The replenishment velocity (ß), plateau of acoustic intensity (A) and myocardial blood flow reserve (MBFR) were determined by quantitative dipyridamole stress RTMCE. RESULTS: ß reserve in group PCOS + IR was lower than control (2.34 ± 0.55 vs. 3.60 ± 0.6; P < 0.001) and than PCOS without IR (2.34 ± 0.55 vs. 3.17 ± 0.65; P < 0.001). MBFR in patients with PCOS without IR did not differ from those of control (4.59 ± 1.59 vs. 5.30 ± 1.64; P = 0.22) or from patients with PCOS + IR (4.59 ± 1.59 vs. 3.70 ± 1.47; P = 0.07). When comparing with control group, patients with PCOS + IR had lower MBFR (5.30 ± 1.64 vs. 3.70 ± 1.47; P = 0.01). No significant differences were found between control, PCOS without IR and PCOS + IR for FMD (0.18 ± 0.05, 0.15 ± 0.04 and 0.13 ± 0.07; P =NS) or IMT (0.48 ± 0.05, 0.47 ± 0.05 and 0.49 ± 0.07; P = NS). CONCLUSION: Women with PCOS and IR had depressed ß and MBFR as demonstrated by quantitative RTMCE, but no alteration in endothelial dysfunction or IMT. PCOS without IR showed isolated depression in ß reserve, probably an earlier marker of myocardial flow abnormality.

Oncological repercussions of polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a highly prevalent endocrine disorder that has been associated with insulin resistance and metabolic syndrome. Evidence has suggested that PCOS may be associated with the appearance of certain types of cancer, particularly endometrial, ovarian and breast cancer. The objective of this review was to collect further evidence of these correlations and to identify their possible mechanisms.

Consumption of a flaxseed-rich food is not more effective than a placebo in alleviating the climacteric symptoms of postmenopausal women.

Our objective in this work was to test the effects of daily intake of bread produced with partially defatted ground flaxseed on the climacteric symptoms and endometrial thickness of postmenopausal women. A double-blind, placebo-controlled, randomized clinical trial was performed with 38 women who had been postmenopausal for 1-10 y and consumed 2 slices of bread containing 25 g of flaxseed (46 mg lignans) or wheat bran (<1 mg lignans; control) every day for 12 consecutive weeks. The outcome variables were the daily number of hot flashes, the Kupperman Menopausal Index (KMI), and endometrial thickness. The plasma lipid profile (total cholesterol and HDL, LDL, and VLDL cholesterol fractions and triglycerides) and the hormones estradiol, follicle-stimulating hormone, thyroid-stimulating hormone, and free thyroxine also were measured. Food intake was evaluated by means of 2 24-h recalls, before and after the treatment. Twenty patients in the study group and 18 in the control group completed the study. The general characteristics did not differ between the 2 groups at the start of the study. Both had significant, but similar, reductions in hot flashes and KMI after 3 mo of treatment. Moreover, endometrial thickness was not affected in either group. Our findings clearly show that although flaxseed is safe, its consumption at this level (46 mg lignans/d) is no more effective than placebo for reducing hot flashes and KMI.

Highlights from the I international symposium of thrombosis and anticoagulation in internal medicine, October 23-25, 2008, Sao Paulo, Brazil.

The importance of thrombosis and anticoagulation in clinical practice is rooted firmly in several fundamental constructs that can be applied both broadly and globally. Awareness and the appropriate use of anticoagulant therapy remain the keys to prevention and treatment. However, to assure maximal efficacy and safety, the clinician must, according to the available evidence, choose the right drug, at the right dose, for the right patient, under the right indication, and for the right duration of time. The first International Symposium of Thrombosis and Anticoagulation in Internal Medicine was a scientific program developed by clinicians for clinicians. The primary objective of the meeting was to educate, motivate and inspire internists, cardiologists and hematologists by convening national and international visionaries, thought-leaders and dedicated clinician-scientists in Sao Paulo, Brazil. This article is a focused summary of the symposium proceedings.

Prevalence of endometrial cancer and hyperplasia in non-symptomatic overweight and obese women.

BACKGROUND: Obesity is a public health problem and it is necessary to identify if non-symptomatic obese women must be submitted to endometrial evaluation. AIMS: To determine the prevalence of endometrial hyperplasia and cancer in non-symptomatic overweight or obese women. METHODS: A cross-sectional study was carried out in 193 women submitted to an endometrial biopsy using a Pipelle de Cornier. The findings were classified as normal, hyperplasia or cancer, and the results were compared to body mass index (BMI; kg/m(2)). For the purpose of statistical analysis, women were divided into two groups: women of reproductive age and postmenopausal women, and according to BMI as overweight or obese. RESULTS: The prevalence of endometrial cancer and hyperplasia was 1.0% and 5.8% in women of reproductive age and 3.0% and 12.1% in postmenopausal women, respectively. According to logistic regression, being in the postmenopause increased the risk of endometrial hyperplasia and cancer to 1.19 (95% confidence interval (CI): 0.36-3.90), while being postmenopausal and severely obese increased the odds ratio (OR) to 1.58 (95%CI: 0.30-8.23) and being postmenopausal and morbidly obese increased the OR to 2.72 (95%CI: 0.65-11.5). No increase in risk was found in women of reproductive age who were either overweight or obese. DISCUSSION: Our results show that non-symptomatic, severe or morbidly obese postmenopausal women have a high risk of developing endometrial hyperplasia or cancer; however, no such risk was found for women of reproductive age.

Acute administration of 17beta-estradiol reduces endothelin-1 release during pacing-induced ischemia.

OBJECTIVES: To assess whether acute administration of 17beta-estradiol reduces pacing-induced cardiac release of endothelin-1 in female menopausal patients with coronary artery disease. BACKGROUND: Endothelin-1 is a potent vasoactive peptide which plays a pathogenetic role in myocardial ischemia and adverse clinical events in patients with coronary artery disease. Estrogens decrease plasma levels of endothelin-1 and improve stress-induced myocardial ischemia in menopausal women with coronary artery disease. METHODS: Twenty-two postmenopausal women with angiographically proven coronary artery entered a randomized, double blinded, placebo-controlled study. Patients were sampled into the coronary sinus and aorta for endothelin-1 at baseline and after incremental pacing. After baseline study, patients were randomized to receive either sublingual 17beta-estradiol (1 mg) or placebo and underwent the sampling protocol 20 min thereafter. RESULTS: 17Beta-estradiol but not placebo improved the time of onset of myocardial ischemia during pacing. The coronary sinus plasma levels of endothelin-1 were significantly reduced by estradiol administration but not by placebo, at each step of pacing protocol. The maximum reduction of endothelin-1 was noted at peak pacing (-0.18 ng/l; -0.09, -0.3; 95% CI). No changes in endothelin-1 were noted in patients allocated to placebo (-0.002 ng/l; -0.06, -0.01; 95% CI). Similarly, aorto-coronary sinus difference of endothelin-1 was significantly influenced by 17beta-estradiol administration but not by placebo. CONCLUSION: Acute administration of 17beta-estradiol reduces pacing-induced cardiac release of endothelin-1 in postmenopausal women with coronary artery disease. This result may be related to the anti-ischemic or to a primary direct effect of the hormone upon myocyte release of the peptide, and may contribute to its anti-ischemic effect. CONDENSED ABSTRACT: To assess effect of acute 17beta-estradiol administration on pacing-induced cardiac release of endothelin-1, we studied 22 female menopausal patients with coronary artery diseases. In a randomized, double-blinded, placebo-controlled study, patients were randomized to receive either sublingual 17beta-estradiol (1 mg) or placebo. Aortic and coronary sinus plasma endothelin-1 levels were evaluated at baseline, during incremental atrial pacing, and at peak pacing before and after the sublingual administration of either 17beta-estradiol or placebo. The time to the onset of myocardial ischemia during pacing was significantly increased by 17beta-estradiol vs. placebo. Moreover, coronary sinus endothelin-1 levels at peak pacing and aortic-coronary sinus changes were significantly improved by the administration of 17beta-estradiol but not by placebo. Acute administration of 17beta-estradiol reduces pacing-induced cardiac release of endothelin-1 in postmenopausal women with coronary artery disease.

Effect of a combination of ethinylestradiol 30 microg and drospirenone 3 mg on tolerance, cycle control, general well-being and fluid-related symptoms in women with premenstrual disorders requesting contraception.

PURPOSE: Positive effects on premenstrual symptoms have been observed with low-dose oral contraceptives. Drospirenone is a synthetic progestogen with antiandrogenic and antimineralocorticoid effects. This open-label, multicenter study evaluated the effects of a combination of ethinylestradiol 30 microg and drospirenone 3 mg on safety, cycle control, general well-being and fluid-related symptoms in women with premenstrual disorders requesting contraception. MATERIALS AND METHODS: A total of 241 healthy volunteers with symptoms of premenstrual disorder was enrolled in the study. Of the final sample, 203 completed the six-cycle treatment and were included in the efficacy analysis whereas 236 were included in the tolerability analysis. The subjects recruited to the study were required to fill up the Psychological General Well-Being Index (PGWBI). RESULTS: There was no significant change in body weight or blood pressure throughout the treatment. Adverse events reported by patients during treatment consisted of those already known to be associated with oral contraceptive use. PGWBI scores were significantly higher after six cycles of treatment compared with baseline values (p<.0001). A total of 198 (84.2%) subjects reported a great improvement in premenstrual symptoms. CONCLUSIONS: The results of this study confirm that oral use of a combination of ethinylestradiol 30 microg and drospirenone 3 mg provides good cycle control, is well tolerated and has a positive impact on symptoms of premenstrual disorder.

Subfascial transaxillary breast augmentation without endoscopic assistance: technical aspects and outcome.

BACKGROUND: Although transaxillary breast augmentation (TBA) is a well-studied procedure, few previous reports exist concerning the subfascial technique, especially without endoscopic assistance. This study aimed to analyze the feasibility of the technique after breast augmentation in terms of its indication, surgical technique, limitations, and clinical outcome. METHODS: For this study, 42 patients underwent TBA without endoscopic assistance. The technique was indicated for patients with breasts of small or moderate volume without ptosis, patients who wanted no breast scars, and patients who had a poorly defined inframammary fold. The mean follow-up period was 16 months. Implant and incision approach complications were evaluated. Information on patient satisfaction was collected. RESULTS: A total of 14 complications occurred in 42 patients, all of them minor. Axillary incision-related complications occurred in 26% of the patients, as represented by a late axillary subcutaneous band (119%), sensory loss in the inner aspect of the arm (71%), and a hypertrophic scar and small wound dehiscence (71%). No patient presented with capsular contracture, visible rippling, or infection. Most of the patients (93%) were either very satisfied or satisfied with their result, and none regretted the surgery. CONCLUSION: The TBA procedure without endoscopic assistance is a simple and reliable technique for breast augmentation. Most of the complications in this study were minor and predictable. They did not interfere with the aesthetic outcome nor the normal postoperative recovery. With TBA, success depends on patient selection as well as careful intra- and postoperative management.

Platelet activation status decreases after menopause.

OBJECTIVE: The aim of the study was to investigate the impact of the climacterium (before and after menopause) on platelet activation. BACKGROUND: Platelet activation has been associated to the risk of cardiovascular disease. There is much speculation about the relationship between platelet function and sex steroids, due to peculiarities of platelet action between the genders, including concerns about the influence of low estradiol status in menopausal women. METHODS: By means of a cross-sectional study design, 37 female patients divided into two groups were compared. Group A consisted of ten women, mean age 43.9 years, in the premenopausal period, with normal estrogen levels; and Group B comprised 27 patients, mean age 53.0 years, who had all reached menopause. Platelet activation markers, namely P-selectin and glycoprotein IIb-IIIa complex (GPIIb-IIIa), were evaluated by flow cytometry with monoclonal antibodies. A binding index was calculated for both parameters (percentage of positive platelets x mean fluorescence of positive platelets). Also, thromboxane A2 was quantified by means of its main plasma metabolite, thromboxane B2, by enzyme immunoassay. RESULTS: P-selectin and GPIIb-IIIa expression results revealed lower platelet activation status after menopause, as there was a decrease in both the percentage of P-selectin+ platelets and of GPIIb-IIIa mean fluorescence of positive platelets, lowering both binding indices. P-selectin binding index differed significantly between Group A (12.3 +/- 3, n = 10) and Group B (6.2 +/- 2.9, n = 27; mean +/- standard deviation (SD), p < 0.001). GPIIb-IIIa binding index also differed significantly between both groups (Group A: 18.8 +/- 2.3, n = 10 vs. Group B: 16.2 +/- 3.1, n = 27; mean +/- SD, p < 0.0018). Plasma concentration of thromboxane B2 was 1.07 +/- 0.5 pg/well before menopause (Group A, n = 10) and 1.9 +/- 4.1 pg/well after menopause (Group B, n = 27), not significantly different (mean +/- SD, baseline x therapy, p = 0.85). CONCLUSIONS: After the menopause, climacteric women--whose estradiol status is low--have a decreased activation platelet status compared with premenopausal women. Nevertheless, further studies on a larger sample are necessary for conclusive data regarding cardiovascular disease.

[Quality of life in users and non-users of hormone replacement therapy]. / Qualidade de vida em usuárias e não usuárias de terapia de reposição hormonal.

OBJECTIVE: To compare the quality of life in postmenopausal women who were users and non-users of hormone replacement therapy (HRT). METHODS: A cross-sectional study was conducted on postmenopausal women aged between 40 and 65 years, who had been menopausal for up to 15 years. Women considered HRT users were those who had undergone this type of treatment for at least six months. Non-users of HRT were those who had not received this type of treatment during the last six months. Two hundred and seven women were included in the study: 106 users and 101 non-users of HRT. Sociodemographic, clinical and behavioral characteristics were assessed. The Kupperman Menopausal Index was applied to rate the intensity of climacteric symptoms and the Medical Outcomes Study 36-item Short-Form Health Survey (SF-36) was applied to assess women's quality of life. For data analysis, a Student's t test, a chi-square analysis, a Fisher's exact test and a Mann-Whitney test were used. RESULTS: The mean age of HRT users was 52.6 +/- 4.9 years and the mean age of non-users of HRT was 54.3 +/- 4.7 years (p=0.01). There was a statistically significant difference regarding marital status (p=0.04). HRT users reported a lower frequency of moderate and severe climacteric symptoms (p=0.001). Of the eight quality of life domains evaluated, only vitality scored below 50 (45) in both groups. There were no differences between groups regarding the SF-36 components. CONCLUSIONS: Postmenopausal women who were users and non-users of HRT presented a good quality of life. There were no differences between users and non-users of hormone therapy.

Qualidade de vida em usuárias e não usuárias de terapia de reposição hormonal / Quality of life in users and non-users of hormone replacement therapy

OBJETIVO: Comparar a qualidade de vida de mulheres após a menopausa usuárias e não usuárias de terapia de reposição hormonal (TRH). MÉTODOS: Realizou-se um estudo de corte transversal com mulheres na pós-menopausa, com idade entre 40 e 65 anos, menopausadas há no máximo 15 anos. Consideraram-se como usuárias de TRH aquelas que faziam uso dessa terapia há pelo menos seis meses, e não usuárias aquelas que não fizeram uso dessa terapia nos últimos seis meses. Foram incluídas no estudo 207 mulheres: 106 usuárias e 101 não usuárias de TRH. Avaliaram-se as características sociodemográficas, clínicas e comportamentais. Aplicou-se o índice de Kupperman para avaliar a intensidade dos sintomas climatéricos, e o questionário Medical Outcomes Study 36-item Short-Form Health Survey (SF-36) para avaliação da qualidade de vida. Na análise dos dados utilizaram-se os testes t de student, Qui-quadrado, exato de Fisher e Mann-Whitney. RESULTADOS: As usuárias de TRH apresentaram média etária de 52,6±4,9 anos e as não usuárias de 54,3±4,7 anos (p=0,01). Houve diferença estatisticamente significativa em relação ao estado marital (p=0,04). As usuárias relataram menor freqüência de sintomas climatéricos de intensidade moderada e acentuada (p=0,001). Dos oito domínios de qualidade de vida avaliados, apenas a vitalidade apresentou escore abaixo de 50 (45) para os dois grupos. Não houve diferenças entre os grupos em relação aos componentes do SF-36. CONCLUSÕES: As mulheres na pós-menopausa usuárias e não usuárias de TRH apresentaram boa qualidade de vida. Não houve diferenças entre usuárias e não usuárias de terapia hormonal.

Postmenopausal hormone replacement therapy increases plasmatic thromboxane beta 2.

OBJECTIVE: This study shows the effect of hormone replacement therapy (HRT), using oral estrogen exclusively or in combination with progestin, on platelet activation in healthy menopaused women. BACKGROUND: Recent evidence from studies of postmenopausal HRT in healthy women demonstrated a short-time increased risk of coronary heart disease. Platelet activation, which generates vasoconstrictory thromboxane A(2) (TxA(2)), has been related to the risk of cardiovascular diseases. METHODS: By means of a placebo-controlled study twenty-seven postmenopausal patients were continuously orally administered estrogen in combination with progestin or estrogen exclusively for an 8-week period. Platelet activation was evaluated by flow cytometric P-selectin expression and by enzyme immunoassay plasmatic TxA(2) (TxB(2)) concentrations. RESULTS: P-selectin binding index changed from 6.3+/-3.6 to 7.0+/-3 in the placebo group (n=10); from 5.9+2.2 to 7.9+/-3.3 in the E+P group (n=8) and from 6.4+2.7 to 7.1+/-1.9 in the E group (n=9). Plasma concentrations of TxB(2) before and after intervention, changed from 1.2+1.2 to 1.5+1.4 (pg/well) in the placebo group; significantly (p=0.005) in the E+P group (n=8), from 0.9+0.3 to 6.1+6.5 (pg/well), and from 1.3+1.5 to 0.8+0.4 (pg/well) in the E group (n=8; mean+standard deviation, basal x therapy, p<0.05). CONCLUSIONS: Healthy menopaused women who were administered estradiol in association with norethisterone continuously had an increase of plasmatic thromboxane, possibly determined by platelet activation, which indicates a higher short-term thrombotic risk. P-selectin expression analyses failed to demonstrate the impact of HRT on platelets.

Estrogen replacement and exercise capacity in postmenopausal women: a randomized placebo-controlled study.

OBJECTIVE: We tested the hypothesis that estrogen replacement (2 mg estradiol/day, orally for 90 days) would improve cardiopulmonary and functional capacities in postmenopausal women. STUDY DESIGN: Twenty-three postmenopausal and sedentary women were divided into estrogen replacement (n = 13, 57 +/- 2 years) and placebo control (n = 10, 58 +/- 2 years) groups. They performed a cardiopulmonary exercise test before and after the intervention. RESULTS: Baseline measurements were similar between groups. Blood pressure and heart rate at rest and during exercise were unchanged by estrogen treatment, and estrogen did not alter pulmonary measurements at rest and during exercise. Oxygen consumption at anaerobic threshold, respiratory compensation point and peak exercise were lower after estrogen replacement, despite the unchanged workload and exercise time to exhaustion. In the placebo control group, no change in peak oxygen consumption, workload and time to exhaustion was found. CONCLUSIONS: Estrogen does not change cardiopulmonary responses to submaximal and maximal exercise in postmenopausal women. In addition, estrogen fails to improve exercise capacity in postmenopausal women.

Predictors of hot flushes in postmenopausal women who receive raloxifene therapy.

OBJECTIVE: In a previous report, we described the results of a randomized, controlled trial that evaluated the potential of raloxifene to induce or exacerbate hot flushes. Here, we provide additional analyses that were undertaken to identify potential predictors of hot flushes and to assess the clinical usefulness of various therapeutic strategies for the reduction of hot flushes in postmenopausal women who receive raloxifene therapy. STUDY DESIGN: In this randomized, double-blind, placebo-controlled study, 487 unselected postmenopausal women were assigned randomly to receive treatment for 8 months with raloxifene, which was administered either at a dose of 60 mg/d every other day for 2 months followed by 60 mg/d (slow-dose escalation) or 60 mg/d throughout (raloxifene), or placebo. Data on the number, duration, intensity, and severity of hot flushes and awakenings because of night sweats were collected. Logistic regression models were used to examine the predictive value of various demographic and menopausal factors on the development or worsening of hot flushes. RESULTS: At baseline, 40.4% of all randomly assigned patients had hot flushes. The mean number of hot flushes (3-5 per week) was low. Fewer years postmenopause, surgical menopause, and previous estrogen or estrogen/progestin therapy were significant predictors of hot flushes at baseline but were not predictive of incident hot flushes during treatment with raloxifene. Of the women who received raloxifene therapy who had pre-existing hot flushes at baseline, 36% women had none at the end point. Early postmenopause and surgical menopause were significant predictors of a biologically relevant increase in hot flushes (>/=14 flushes/week). Early postmenopause, previous estrogen/progestin therapy, high body mass index, and greater duration of hot flushes at baseline were significant predictors of the need for symptomatic treatment. After 2 months of treatment, women in early postmenopause had significantly more hot flushes with raloxifene therapy than with slow-dose escalation ( P = .042), whereas there was no significant difference between raloxifene therapy and slow-dose escalation among women in later postmenopause. In the 50 patients who requested symptomatic treatment during the study, phytohormones or veralipride did not reduce the number of hot flushes markedly. CONCLUSION: A shorter time since menopause and surgical menopause are important predictors of hot flushes both before and during treatment with raloxifene. Previous estrogen/progestin therapy also increases the risk of hot flushes at baseline. For women in early postmenopause, slow-dose escalation of raloxifene therapy may be a suitable therapeutic strategy for the reduction of the risk of hot flushes.