Effect of hormone therapy, tibolone and raloxifene on circulating vascular endothelial growth factor in Greek postmenopausal women

OBJECTIVE: To evaluate the effect of continuous combined hormone therapy (HT), tibolone and raloxifene on circulating vascular endothelial growth factor (VEGF) in postmenopausal women. DESIGN: One-year prospective intervention study. METHODS: One hundred and forty-six postmenopausal women with a mean age of 51.8+/-4.1 (s.d.) years received 0.625 mg conjugated equine estrogen (CEE) plus 5 mg medroxyprogesterone acetate (MPA) (CEE/MPA, n=34), 2.5 mg tibolone (n=37), 60 mg raloxifene (n=40) or no active treatment (control group, n=35). Plasma VEGF was estimated at baseline and at 6 and 12 months. RESULTS: In both the CEE/MPA-treated and the tibolone-treated groups plasma VEGF increased significantly at month 6 and remained elevated at month 12 (CEE/MPA baseline: 268.1+/-187.8 pg/ml, month 6: 320.0+/-175.3 pg/ml, month 12: 321.1+/-181.8 pg/ml, P=0.01; tibolone baseline: 240.6+/-165.8 pg/ml, month 6: 271.4+/-172.7 pg/ml, month 12: 274.8+/-183.1 pg/ml, P=0.03). These changes were significantly different from the respective changes in the control group after adjusting for T-score in bone densitometry (CEE/MPA: P=0.02, tibolone: P=0.04). The effect of HT or tibolone on plasma VEGF was mainly evident in women with low baseline VEGF levels (<243.2 pg/ml, median for whole sample). On the contrary, VEGF levels in the raloxifene-treated or the control group did not change throughout the study. CONCLUSION: Both continuous combined HT and tibolone increased circulating VEGF in postmenopausal women, while raloxifene had no effect. Further research is needed to clarify the clinical relevance of these findings with respect to cardiovascular risk in postmenopausal women.     

Combined hormone replacement therapy improves endothelial function in healthy postmenopausal women

OBJECTIVES: Large scale epidemiological studies suggest that hormone replacement therapy (HRT) reduces cardiovascular events in postmenopausal women. Improvement in endothelial function may contribute to this protective effect. DESIGN: In a prospective, double blind study, 61 healthy postmenopausal women were randomized to receive either oral continuous combined HRT [oestradiol 2 mg and norethisterone acetate (NETA) 1 mg per day] or placebo. Endothelial function, assessed by flow-mediated vasodilation (FMD) of the brachial artery and expression of soluble endothelial cell adhesion molecules (CAM) were determined before, after 3 and 6 months of therapy. RESULTS: The FMD was significantly improved in women on combined HRT (from 5.97% to 10.94% after 3 months and to 10.58% after 6 months; both P < 0.01 versus baseline values) and did not change in the placebo group (6.92% at baseline, 5.86% after 3 and 6.26% after 6 months). After 3 months of combined HRT, significant decreases of 24.6% for E-selectin and 13.9% for intercellular adhesion molecule-1 (ICAM-1) were observed (both P < 0.01 versus baseline values) and were sustained after 6 months of therapy, whilst no differences emerged in the placebo group. CONCLUSIONS: Oestradiol and norethisterone acetate improve endothelial function by both enhancing FMD and reducing the levels of soluble E-selectin and ICAM-1 in healthy postmenopausal women.     

Efficacy of sequential hormone replacement therapy in the treatment of hypercholesterolemia among postmenopausal women

Abstract. Objectives. To test the efficacy of hormone replacement therapy (HRT) and dietary therapy, compared to dietary therapy, in lowering LDL cholesterol levels among postmenopausal women. Design. A prospective parallel randomized study of sequential 17β-oestradiol and norethisterone acetate or placebo for 48 weeks. Setting. A University outpatient lipid clinic. Subjects. A total of 76 postmenopausal women, aged 43–60 years, with LDL cholesterol level ≥ 4.2 mmol I^?1 treated with a lipid-lowering diet. Main outcome measures. Levels of lipids, lipoproteins, apolipoproteins, fibrinogen and glucose tolerance. Results. Adherence to the diet was similar in both groups. Total and LDL cholesterol levels were reduced by 14% (95% CI, 11–17%) and 19% (95% CI, 14–23%), respectively, in the HRT group vs. 3% (95% CI. 0–7%) and 5% (95% CI, 0–11%) in the diet group. HRT reduced the levels of apolipoprotein B and lipoprotein(a). Levels of HDL cholesterol, HDL₂, HDL₃, triglycerides, lipoprotein populations and apolipoproteins. AI and AII remained unchanged. No adverse effects on glucose tolerance or on fibrinogen levels were observed. The reduction in LDL cholesterol was positively correlated with initial levels of LDL cholesterol and negatively correlated with body mass index. Conclusions. HRT is effective in reducing elevated LDL cholesterol levels, and should be considered in the treatment of hyperlipidaemic postmenopausal women, in addition to dietary therapy.     

Different circulatory response to melatonin in postmenopausal women without and with hormone replacement therapy

In young men and women, melatonin influences vascular reactivity and reduces blood pressure and norepinephrine levels. Herein, we investigated whether these effects are conserved in postmenopausal women without and with hormone replacement therapy (HRT). Oral melatonin (1 mg) or placebo was randomly and in double blind fashion administered to 18 untreated and 13 postmenopausal women who were treated continuously with transdermal estradiol (50 microg/day) plus cyclic medroxyprogesterone acetate (5 mg/day x 12 days every 28 days). Internal carotid artery pulsatility index (PI), an index of downstream resistance to blood flow, blood pressure and catecholamine levels were evaluated. In untreated postmenopausal women, melatonin was ineffective, while in HRT-treated women, studied during the only estrogenic phase, melatonin reduced, within 90 min, systolic (-8.1 +/- 9.9 mmHg; P = 0.054), diastolic (-5.0 +/- 7.0 mmHg; P = 0.049) and mean (- 6.0 +/- 6.6 mmHg; P = 0.037) blood pressure. Norepinephrine (-50.1 +/- 66.7 pg/mL; P = 0.019), but not epinephrine levels, were also significantly reduced. Similarly, resistance to blood flow in the internal carotid artery, as evaluated by the PI, decreased (-0.190 +/- 0.15; P = 0.0006) in a way that was linearly related to pre-existing PI values (r2 = 0.5; P = 0.0059). These data show that the circulatory response to melatonin is conserved in postmenopausal women on HRT but not in untreated postmenopausal women. Possible physiological and pharmacological implications of these data on the cardiovascular risk of postmenopausal women can be envisioned.     

Use of hormone replacement therapy by postmenopausal women in the United States

BACKGROUND: The benefits and risks of hormone replacement therapy (HRT) in postmenopausal women are not fully defined, and individual characteristics and preferences may influence decisions to use this therapy. Previous studies of postmenopausal women who use HRT have been conducted in local or highly selected cohorts or have not focused on current use. OBJECTIVE: To examine sociodemographic, clinical, and psychological factors associated with current use of HRT in a national population-based cohort. DESIGN: Random-digit telephone survey. SETTING: Probability sample of U.S. households with a telephone. PARTICIPANTS: 495 postmenopausal women 50 to 74 years of age in 1995. MEASUREMENTS: Current use of HRT. RESULTS: Current use of HRT was reported by 37.6% of women (58.7% of those who underwent hysterectomy and 19.6% of those who did not undergo hysterectomy; P = 0.001). In multivariable analyses, use of HRT was more common among women in the South (adjusted odds ratio, 2.67 [95% CI, 1.08 to 6.59]) and West (odds ratio, 2.76 [CI, 1.01 to 7.53]) than the Northeast. Use was more common among college graduates (odds ratio, 3.72 [CI, 1.29 to 10.71]) and less common among women with diabetes mellitus (odds ratio, 0.17 [CI, 0.05 to 0.51]). Other cardiac risk factors and most psychological characteristics were not associated with HRT use. CONCLUSIONS: Sociodemographic factors, such as region and education, may be more strongly associated with use of HRT than clinical factors, such as risk for cardiovascular disease. Future efforts should focus on understanding sociodemographic variations, defining which women are most likely to benefit, and targeting therapy to them.     

绝经妇女激素替代治疗观点的历史演变

随着妇女平均寿命的延长 ,绝经后的问题日益受到全社会的广泛关注 ,旨在改善妇女生活质量的激素替代治疗(ＨＲＴ)所引发的问题也不断涌现 ,ＨＲＴ对绝经后妇女的生活质量究竟是否有总体益处已成为目前关注的焦点。 2 0 0 2年 7月 9日 ,美国国立卫生研究院 (ＮＩＨ)心脏、肺和血液研究所 (ＮＨＬＢＩ)宣布妇女健康初始行动 (ＷＨＩ)中雌激素加孕激素预防健康绝经后妇女的临床试验由于乳腺癌发病相对风险增加 2 6% ,且并无总体益处予以提前终止 ,这是一项按循证医学进行的重要研究结果 ,将对今后绝经后妇女ＨＲＴ产生重大影响。自从 1963年Ｗ…     

激素替代治疗与绝经后妇女心血管疾病的关系

在绝经前,女性发生心血管疾病的危险性较低,然而,伴随着更年期的到来,女性心血管疾病的发病率明显升高,激素替代治疗随之成为临床上预防心血管疾病的热点话题.激素替代治疗在预防绝经妇女心血管疾病方面的研究.结果 并不一致,其预防效果在一定程度上取决于接受治疗者个体情况的差异.因此,激素替代治疗应当注意用药的时间、用药的个体化...     

行激素补充疗法的绝经后妇女子宫内膜安全性监测

目的　探讨应用激素补充疗法(HRT)的绝经后妇女子宫内膜安全性的监测方法。　方法　对60例绝经后行HRT妇女进行血清雌二醇(E2)测定;阴道B超(TVS)监测子宫体积和子宫内膜厚度;对部分患者行子宫内膜的病理学检查和雌激素受体(ER)、孕激素受体(PR)半定量检测。　结果　应用HRT后,子宫内膜明显增厚,均值从2.8mm升至3.9mm(P＜0.05);E2显著上升,由(20.6±6.9)ng/L升至(33.8±11.7)ng/L（P＜0.01）;子宫内膜厚度与E2呈正相关关系(r=0.94,P＜0.01);20例送检内膜中,2例简单型增生过长,1例复杂型增生过长,余为萎缩型;ER(+)19例,ER(++)1例;PR均为(+)。　结论　根据临床表现,并结合血清E2和TVS检测子宫内膜厚度,可对子宫内膜安全性进行初步评估;当E2＞45ng/L,子宫内膜厚度≥5mm时,则需进一步行子宫内膜病理学检查和ER测定。     

Effects of hormone replacement therapy on coagulation and fibrinolysis in postmenopausal women

It has been speculated that hormone replacement therapy (HRT) containing relatively low dose of estrogen would be different from oral contraceptive pills in causing thromboembolism because activation of coagulation depends on the amount of estrogen. In contrast to this knowledge, activation of coagulation pathways has been detected in postmenopausal women treated with HRT in the observational and clinical studies. In this regard, recent studies have reported a 2 to approximately 4 fold risk of venous thromboembolism or pulmonary embolism in postmenopausal women receiving HRT than in non-users of estrogen. On the other hands, HRT has shown to enhance systemic fibrinolysis with decreased plasma plasminogen activator inhibitor-1 (PAI-1) levels. In addition, levels of D-dimer exhibited a significant inverse correlation with PAI-1 levels, suggesting enhanced fibrinolysis potential. However, small doses of estrogen/progestogen induce increases in fibrinolytic capacity via a marked reduction of PAI-1. In other words, HRT at conventional dosages may affect fibrinolytic activity to a greater extent than coagulation activity, whereas the converse trend holds at higher estrogen doses. The increase in fibrinolytic potential was independent of any effect on coagulation of CEE at conventional dosages. However, in contrast to healthy postmenopausal women, we recently reported that HRT did not significantly decrease PAI-1 antigen levels and rather, increased tissue factor activity and prothrombin fragment F(1+2) levels from baseline in hypertensive and/or overweight postmenopausal women. Activation of coagulation following HRT may not be balanced by activation of fibrinolysis in some postmenopausal women. Thrombogenic events are considered more likely in patients with certain heritable conditions, such as platelet antigen-2 (PIA-2) polymorphisms. Further, Factor V Leiden mutation increases the risk of primary and recurrent venous thromboembolic events by three to sixfold and the risk of myocardial infarction. Indeed, HRT may decrease or increase atherothrombosis risk depending on the presence of Factor V Leiden mutation. Thus, HRT should not be initiated in women with established coronary artery disease or the coexistence of other risk factors for hypercoagulability-malignancy, immobility, obesity, diabetes, advanced age, or inherited traits. However, HRT at conventional dosages improves fibrinolysis potential in healthy postmenopausal women.     

Effects of hormone replacement therapy on coagulation and fibrinolysis in postmenopausal women

It has been speculated that hormone replacement therapy (HRT) containing relatively low dose of estrogen would be different from oral contraceptive pills in causing thromboembolism because activation of coagulation depends on the amount of estrogen. In contrast to this knowledge, activation of coagulation pathways has been detected in postmenopausal women treated with HRT in the observational and clinical studies. In this regard, recent studies have reported a 2～4 fold risk of venous thromboembolism or pulmonary embolism in postmenopausal women receiving HRT than in non-users of estrogen. On the other hands, HRT has shown to enhance systemic fibrinolysis with decreased plasma plasminogen activator inhibitor-1 (PAI-1) levels. In addition, levels of D-dimer exhibited a significant inverse correlation with PAI-1 levels, suggesting enhanced fibrinolysis potential. However, small doses of estrogen/ progestogen induce increases in fibrinolytic capacity via a marked reduction of PAI-1. In other words, HRT at conventional dosages may affect fibrinolytic activity to a greater extent than coagulation activity, whereas the converse trend holds at higher estrogen doses. The increase in fibrinolytic potential was independent of any effect on coagulation of CEE at conventional dosages. However, in contrast to healthy postmenopausal women, we recently reported that HRT did not significantly decrease PAI-1 antigen levels and rather, increased tissue factor activity and prothrombin fragment F₁₊₂ levels from baseline in hypertensive and/or overweight postmenopausal women. Activation of coagulation following HRT may not be balanced by activation of fibrinolysis in some postmenopausal women. Thrombogenic events are considered more likely in patients with certain heritable conditions, such as platelet antigen-2 (PIA-2) polymorphisms. Further, Factor V Leiden mutation increases the risk of primary and recurrent venous thromboembolic events by three to sixfold and the risk of myocardial infarction. Indeed, HRT may decrease or increase atherothrombosis risk depending on the presence of Factor V Leiden mutation. Thus, HRT should not be initiated in women with established coronary artery disease or the coexistence of other risk factors for hypercoagulability-malignancy, immobility, obesity, diabetes, advanced age, or inherited traits. However, HRT at conventional dosages improves fibrinolysis potential in healthy postmenopausal women.     

Hormone replacement therapy in postmenopausal women

From the endocrine point of view, menopause is considered a deficiency state and menopausal hormone replacement therapy (HRT) regarded as restoring the premenopausal endocrine milieu. Millions of healthy postmenopausal women were taking HRT in late 1990's many in the absence of menopausal symptoms. The major benefit from HRT was considered to be cardiovascular protection and also protection against osteoporosis and Alzheimer's Disease. The Women's Health Initiative (WHI) trial and other studies published since 2002 fundamentally changed our understanding of risks and benefits associated with HRT. This review discusses the effects of HRT on menopausal symptoms, cognitive function, cardiovascular disease, osteoporosis and also breast and bowel cancer.     

The effects of hormone replacement therapy on pulmonary functions in postmenopausal women

Although the effects of hormone replacement therapy (HRT) used after the menopause on the cardiovascular system, bone tissue, mammary gland, endometrium, menopausal symptoms and sexuality has been well known, there are very few studies about the effects of HRT on the pulmonary functions. In this study, we evaluated the effects of HRT on the pulmonary functions. For this purpose the postmenopausal women were randomized into two groups, 0.625 mg conjugated equine estrogens + 5 mg medroxyprogesterone acetate as a HRT was given to the group I (n= 32), and placebo was given to the control group. Pulmonary function tests (PFT) were performed to the all cases by same technician before and three months after the treatment. FVC, FEV1, FEV1/FVC, FEF25-75 and PEF parameters of the groups were compared. There were no statistically significant differences between the two groups considering the age, duration of the menopause and body mass index (BMI) (p> 0.05). There were no statistically significant differences between the groups considering FVC, FEV1, FEV1/FVC and FEF25-75 values of initial and the 3rd months measurements (p> 0.05). But PEF levels of the HRT group were significantly different than the initial values three months after the treatment (4.42 +/- 2.6 and 4.84 +/- 1.1) (p= 0.023). There were no statistically significant differences between the other compared parameters of PFT. As a result among the PFT parameters of the postmenopausal women taking HRT, PEF that was used as on obstruction parameter was found elevated. So, we concluded that more detailed and prospective studies were needed about the effects of HRT on PFT.