Hormone replacement therapy and cardiovascular risk in menopausal women

The incidence of cardiovascular disease (CVD) differs markedly with regard to gender and age. Women have CVD 10 years later than men. Estrogen seems to play a key role in mediating the risk of CVD in women. The relative risk of CVD is lower in women before menopause and equals that of men between the 6th and 7th decade. However the effects of hormone replacement therapy (HRT) on cardiovascular morbidity and/or mortality in postmenopausal women remain controversial. The results of observational studies and randomized trials in post menopausal women are reviewed in this article. They point out the absolute need of large scale prospective randomized clinical studies to quantify the effects of HRT for primary and secondary prevention of cardiovascular disease in particular in non American countries.     

Hormone replacement therapy and cardiovascular risk: the cardiovascular physicians' viewpoint

Abstract. Sufficient evidence has accumulated showing that hormone replacement therapy (HRT) does protect against cardiovascular disease in women, although data regarding the true magnitude of that protection remains incomplete. There is no evidence that HRT increases the risk of hypertension or thromboembolism, and beneficial effects have been found for plasma lipids, clotting factors and cardiovascular haemodynamics. However, the evidence is not convincing of any beneficial effect of HRT in preventing strokes, and concerns about the risk of cancer with HRT remain. Despite this, considerable uncertainty continues to exist amongst clinicians as to the balance of beneficial and harmful effects from administering HRT. Overall, HRT seems to do no harm and may be protective. A much greater awareness of the long-term consequences of the menopause and the potential benefits of HRT should be encouraged so that women (and their doctors) can make informed decisions about their requirements.     

Hormone replacement therapy and inflammation: interactions in cardiovascular disease

Inflammation plays a central role in the pathogenesis of many forms of vascular disease, including atherosclerosis. Atherogenesis begins with endothelial damage, and the damaged endothelium expresses adhesion molecules, chemokines, and proinflammatory cytokines that direct atherosclerotic plaque formation and spill into the circulation as biomarkers of atherosclerotic disease risk. Menopausal hormone therapy, including a variety of estrogen preparations with or without a progestin, has negative modulatory effects on most of these soluble inflammatory markers, including E-selectin, vascular cell adhesion molecule-1, intercellular adhesion molecule-1, monocyte chemoattractant protein-1, and tumor necrosis factor-alpha, inconsistent effects on interleukin-6, and stimulatory effects on transforming growth factor-beta, a vasoprotective cytokine. In contrast, C-reactive protein, a circulating proinflammatory cytokine produced in both liver and atherosclerotic arteries, increases in response to oral conjugated estrogens but not to transdermal estrogen. Although C-reactive protein is clearly linked to increased cardiovascular disease risk in women, the hormone-induced rise in this biomarker is not associated with increased risk and may be related to a first-pass effect of C-reactive protein production in the liver after oral estrogen absorption. Many important questions about the effects of ovarian hormones on vascular inflammation and the pathogenesis of vascular disease cannot be answered in human subjects. Insights from fundamental mechanistic studies in animal models are needed to delineate the cellular/molecular events that determine whether these hormones protect or injure blood vessels.     

Hormone replacement therapy and cardiovascular disease: an evidence based approach

The recently reported results of one of the arms of the Women's Health Initiative (WHI) (the Estrogen + Progestin arm) have sparked a substantial amount of debate and controversy over the interpretation of the study findings and their implications for the practice of medicine, in particular in reference to the role that hormone therapy (HT) has in the prevention of coronary heart disease (CHD). The WHI study is the only large randomized clinical trial that, to date, has addressed the issue of HT in the primary prevention of CHD and has provided evidence that the formulation used in the study does not provide CHD benefits and increases the overall risk for cardiovascular disease. The WHI findings, together with the findings from other clinical trials that have been published since the initiation of WHI, provide no support for HT in cardiovascular disease prevention. Questions regarding different formulations and administration routes still remain, however, the prudent and sensible approach, while we collect the evidence on these important issues, is to refrain from considering HT a viable solution to the prevention of CHD in post-menopausal women.     

Hormone replacement therapy

Hormone Replacement Therapy (HRT) is replacement of depleted endogenous estrogen for postmenopausal women. Usually progestin is used in combination to avoid endometrial proliferation. As for bone metabolism, estrogens exert bone protective effect through inhibition of bone absorption. HRT has been shown to improve bone mineral density and to lower the risk of osteoporotic bone fracture. However, the results of recent large scale clinical studies in the U.S. indicate that HRT not only raise the risk of breast cancer, but also increase the incidence of atherosclerotic cardiovascular diseases. According to these studies, the benefit of HRT does not outweigh its risk except the treatment of postmenopausal vasomotor symptoms. To resolve this problem, low dose HRT and SERM (selective estrogen receptor modulator) regimens are under investigation.     

Hormone replacement therapy and vascular risk disorders in adult hypopituitarism

Adult patients with hypopituitarism are treated by the replacement of deficient hormones, although GH has not been substituted until March 2006 in Japan except for clinical trial. This study examines which hormonal status influences the prevalence of vascular risk disorders in hypopituitary adults. A sample of 263 adult patients with hypopituitarism was studied, among whom there were various hormonal status such as no deficiency, treated or untreated deficiency of each pituitary hormone. Analysis of adult patients with hypopituitarism showed that hypertension was more prevalent in the older than in younger patients and in male than in female patients. Hypercholesterolemia and hypertriglyceridemia were more prevalent in patients with TSH deficiency even with thyroxine substitution than those without TSH deficiency. Both obesity and hypertension were less prevalent in patients with treated ACTH deficiency than those without ACTH deficiency. Obesity was more prevalent in patients with treated vasopressin deficiency than those without vasopressin deficiency. These results provide evidence that glucocorticoid substitution in ACTH deficient adults was favorable to prevent obesity and hypertension but that the thyroxine substitution in TSH deficient adults appeared rather insufficient to prevent hyperlipidemia.     

Hormone replacement therapy and the cardiovascular system lessons learned and unanswered questions

Cardiovascular disease is the leading cause of death among women in the U.S., exceeding breast cancer mortality in women of all ages. Women present with cardiovascular disease a decade after men, and this has been attributed to the protective effect of female ovarian sex hormones that is lost after menopause. Animal and observational studies have shown beneficial effects of hormone therapy when it is initiated early in the perimenopausal period or before the development of significant atherosclerosis. However, randomized, placebo-controlled trials in older women have not shown any benefit in either primary prevention or secondary prevention of cardiovascular events, with a concerning trend toward harm. This review outlines the lessons learned from the basic science, animal, observational, and randomized trials, and then summarizes yet-unanswered questions of hormone therapy and cardiovascular risk.     

Hormone replacement therapy and risk of cardiovascular disease: implications of the results of the Women's Health Initiative

The higher rates of coronary heart disease (CHD), stroke, and venous thrombosis among women taking estrogen and progesterone (E+P) compared with placebo in the Women's Health Initiative clinical trial have important implications for women's health. Previous studies in both men and women have shown that estrogen therapy lowers low-density lipoprotein cholesterol and raises high-density lipoprotein cholesterol. The changes in these lipoproteins should be associated with at least a 30% decline in CHD risk. Estrogens increased very-low-density lipoprotein (VLDL) triglyceride levels and C-reactive protein. There is evidence that estrogens increase thrombin generation and fibrinolysis. The increase in VLDL triglycerides may enhance thrombotic risk as well as higher levels of atherogenic lipoproteins, such as dense low-density lipoprotein. Genetic variations in estrogen receptors and thrombosis or fibrinolysis may also be important in risks associated with E+P therapy. The increased risk of CHD and stroke with E+P therapy may be attributable to rise in VLDL triglycerides and thrombosis.     

Hormone replacement therapy and hypertension

For many years, Hormone Replacement Therapy (HRT) was considered to be contraindicated in postmenopausal women with hypertension and many such women were excluded from HRT because of concerns that HRT may have an adverse effect on blood pressure. This perception was mainly due to the effects of oral contraceptive drugs, especially the oestrogen component, in increasing blood pressure. Differences exist between the formulation and doses of oestrogen preparations used, either as oral contraceptives in premenopausal women (in whom high-dose synthetic oestrogens are used) or as HRT in postmenopausal women (in whom low “replacement” doses of natural oestrogens are used). This is not inconsequential, as postmenopausal women represent the largest category of women at risk for hypertension. The aim of this review is to give a balanced view on the effects of HRT on blood pressure in postmenopausal women.     

激素替代疗法与卒中

激素替代疗法(hormone replacement therapy, HRT)包括给予类固醇性激素,例如雌激素单用或与孕激素联合应用,被广泛用于绝经后女性.HRT有助于缓解更年期症状,并被证实可预防骨质疏松.虽然大多数观察性研究显示HRT可降低心脑血管病风险,但随后的随机对照试验结果却与之相悖.文章从药物种类、用药途径、雌激素剂量、开始时机等方面对HRT与卒中的关系进行了综述.     

Hormone replacement therapy and osteoporosis

Estrogen deficiency is one significant cause of accelerated bone loss in women during and after menopause. Postmenopausal osteoporosis is a major health problem, primarily because of the severe morbidity and mortality associated with osteoporotic fractures. The Women's Health Initiative Study (WHI) reported that hormone replacement therapy (HRT) prevented osteoporotic fractures. The risks and benefits of HRT are complex and require the individual assessment of each woman considering taking HRT. Use of HRT can be considered as a treatment option for osteoporosis but the risks and benefits should be discussed with each individual woman before starting treatment.     

Hormone replacement therapy and associated risk of stroke in postmenopausal women

BACKGROUND: There is little information about the risk of stroke in relation to time since initiation of hormone therapy and in relation to estrogen dose. METHODS: We conducted a population-based case-control study at Group Health Cooperative (GHC), a health maintenance organization in the greater Seattle (Wash) area, to assess the association of hormone replacement therapy with the risks of incident ischemic and hemorrhagic stroke. Cases were all postmenopausal women with incident stroke at GHC during July 1989 through December 1998 (726 ischemic strokes and 213 hemorrhagic strokes). Controls were randomly selected from GHC enrollees and frequency matched to cases on age and calendar year (n = 2525). Hormone use was assessed from computerized pharmacy data. We reviewed the medical record to confirm eligibility and assess other risk factors. RESULTS: After risk factor adjustment, ischemic stroke was not associated with current use of estrogen with progestin (odds ratio [95% confidence interval]: 0.97 [0.69-1.37]) or without (0.94 [0.72-1.23]) compared with never use. Similarly, hemorrhagic stroke was not associated with current use of estrogen with progestin (0.74 [0.43-1.28]) or without (1.06 [0.71-1.56]). However, the risks of ischemic stroke and hemorrhagic stroke were increased 2-fold during the first 6 months of hormone use (ischemic stroke: 2.16 [1.04-4.49], hemorrhagic stroke: 2.20 [0.83-5.81]). Risk of ischemic stroke also increased with estrogen dose (P for trend =.03). CONCLUSION: The transitory increase in risks of ischemic stroke and hemorrhagic stroke associated with initiation of hormone replacement therapy merits further investigation.     

The menopause and HRT. Hormone replacement therapy,cardiovascular and cerebrovascular disease

Historically, research into vascular effects of hormone replacement therapy (HRT) poignantly highlights the difficulties in extrapolating from medical research into clinical practice. Original observational trials encouraged great enthusiasm that HRT was protective against coronary heart disease (CHD) in post-menopausal women. This was supported by a plethora of beneficial mechanistic effects of HRT on the vascular system. In contrast, recent controlled trials have shown that a specific combined oral HRT actually causes a small increased risk of cardiovascular and cerebrovascular events, compared to placebo. The absolute risks were small, yet were accompanied by increased venous thrombosis and breast cancer. Although many controversies still remain regarding the vascular effects of specific types of HRT, currently, in my opinion, all HRT should be considered as causing a small increased risk of vascular events, until proven otherwise. However, the apparent lack of HRT effectiveness in the prevention of vascular disease should not deter enthusiasm for the use of established preventive therapies, especially lifestyle measures.     

Hormone replacement therapy and the cardiovascular system lessons learned and unanswered questions.

Cardiovascular disease is the leading cause of death among women in the U.S., exceeding breast cancer mortality in women of all ages. Women present with cardiovascular disease a decade after men, and this has been attributed to the protective effect of female ovarian sex hormones that is lost after menopause. Animal and observational studies have shown beneficial effects of hormone therapy when it is initiated early in the perimenopausal period or before the development of significant atherosclerosis. However, randomized, placebo-controlled trials in older women have not shown any benefit in either primary prevention or secondary prevention of cardiovascular events, with a concerning trend toward harm. This review outlines the lessons learned from the basic science, animal, observational, and randomized trials, and then summarizes yet-unanswered questions of hormone therapy and cardiovascular risk.