Use of hormone replacement therapy. Hormone replacement therapy may not always be right choice to prevent cardiovascular disease.
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Current perspectives on benefits and risks of hormone replacement therapy.
Hormone replacement therapy with estrogen alone or with added progestin relieves menopausal symptoms and physical changes associated with depleted endogenous estrogen levels. Estrogen replacement has also demonstrated a clear benefit in the prevention of osteoporosis. Hormone replacement therapy with added progestin maintains spinal bone density, protects against postmenopausal hip fractures, and provides these benefits even when therapy is started after age 60. More recently, additional benefits have emerged. Current estrogen and hormone replacement therapy users have a 34% reduction in the risk of colorectal cancer and a 20% to 60% reduction in the risk of Alzheimer's disease. Until recently, the body of evidence indicated that hormone replacement therapy with estrogen only reduced cardiovascular disease risk by 40% to 50% in healthy patients; whether the findings of 3 ongoing trials will change this conclusion is pending availability of the final results. The many benefits of estrogen and hormone replacement therapy must be weighed against a slight increase in the risk of breast cancer diagnosis with use for 5 or more years, but which disappears following cessation of therapy. Overall, estrogen and hormone replacement therapy improves the quality of life and increases life expectancy for most menopausal women.
Alzheimer Disease↗
Update: the latest on hormone replacement therapy.
Hormone replacement therapy in menopausal women offers many potential health benefits. Only 15% of patients who are eligible for therapy continue treatment past 3 months. Fear and misinformation prevent them from initiating therapy, and side effects prompt them to discontinue taking their medication. This article reviews menopause and hormone replacement with emphasis on the risks, benefits, and hazards of therapy. New options for treatment are explored.
Cardiovascular Diseases↗
Compliance to hormone replacement therapy.
Hormone replacement therapy (HRT) after menopause can effectively reduce climacteric-related symptoms and therefore increase quality of life. A large number of studies have also demonstrated that with a sufficient dosage bone loss can be prevented and fracture frequency reduced. Epidemiological and experimental studies also suggest a decrease in cardiovascular mortality and morbidity among HRT users compared to nonusers. From an epidemiological perspective, in order to obtain optimal prevention of osteoporosis and of cardiovascular diseases, a high proportion of postmenopausal women should be treated using long-term therapy. Surveys generally show that only a small proportion of postmenopausal women use hormone replacement therapy (in Belgium, around 14%) and that the long-term compliance to treatment, which is mandatory in the prevention due to low compliance remains unknown. The reasons why patients patients do not pursue their treatment in the long run remain unclear. Fear of cancer and drug-related side effects, such as unacceptable bleeding, have been among the most frequently mentioned causes. Thus, individual information on patients regarding HRT seems to be crucial issue. A few recent studies have suggested a favorable role of osteoporosis prevention and bone mass measurements to increase compliance, but this is not well established and will depend on the physician's attitude toward HTR and osteoporosis prevention. At present, very little is known about the physician's decision to treat postmenopausal women with HRT. Sometimes, the physician's attitude has been reported was very negative toward HRT-apparently, many physicians think HRT increases cardiovascular risk, even though most data suggest a reduction of cardiovascular risk among HRT users. Very little research has actually been performed on how to improve compliance. Education and behavioral strategies may be of use. Improved communication between patients and physicians, establishing a confidential relationship with patients, and the involvement of nursing counseling are all strategies which may improve compliance. The use of easy-to-take medication that induces no bleeding, supported by calendar devices or reminders, may facilitate chronic use of medication. Future research needs to investigate the physician's and patient's decision-making processes and the reasons for those decisions.
Estrogen Replacement Therapy↗
Menopausal depression: comparison of hormone replacement therapy and hormone replacement therapy plus fluoxetine.
BACKGROUND: To compare the efficacy and safety of hormone replacement therapy (HRT) combined with fluoxetine, with HRT alone, in post-menopausal women suffering from depression. METHODS: A randomized, open-label, parallel trial was applied. HRT was administered to all patients for 2 cycles, with 14 days of estrogen therapy and 14 days of estrogen plus progesterone. Patients who were randomly assigned to the HRT plus fluoxetine group were given fluoxetine in combination with HRT. Hamilton Depression Rating Scale (HAMD), Kupperman Menopausal Index (KMI), and Clinical Global Impressions scale were used to measure the efficacy. RESULTS: One hundred and twenty-three post-menopausal patients with depression were enrolled in the study. Among them, 120 had at least one post-treatment visit and entered into the statistical analysis. The mean total HAMD scores were significantly lower, and the percentages of HAMD score reductions were higher in the HRT plus fluoxetine Group compared with the HRT Group, after at least 3 weeks of treatment, with an average difference of 5 points at the endpoint. The Clinical Global Impression-Severity and Clinical Global Impression-Improvement scores were significantly different in the 2 groups, in favor of the combination therapy. The mean total KMI was significantly lower in the Combination Group compared with the HRT Group, after at least 6 weeks of treatment, with an average 4.5-point difference between the groups. No statistically significant differences were found in most of the adverse events reported in the Combination Group compared with the HRT group, with the exception of 3 symptoms, i.e., dry mouth, loss of appetite, and abdominal distention. They were mild to moderate in severity. Two patients in the HRT group, but none in the combination group, dropped out due to adverse events. CONCLUSION: HRT plus fluoxetine therapy was effective in the treatment of menopausal depression with a satisfactory safety profile.
Adult↗
[Osteoporosis and hormone replacement therapy].
Hormone replacement therapy prevents bone loss and the increase in bone resorption due to the hormone deficiency in oestrogen in postmenopausal women. The WHI (Women's Health Initiative) randomised, double-blind study against placebo, demonstrated that which all the epidemiological trials had already suggested: replacement therapy can reducing by around 30% the risk of fractures in postmenopausal women. Administration of hormone replacement therapy requires account being taken of (in view of the uncertainties regarding the anti-fracture effect of low dose therapy): the duration (in view of the absence of remnant effect of the product on bone loss and on the risk of fracture) and the benefit/risk ration (in view of the benefits demonstrated on climacteric disorders, but the increase in risk of breast cancer). The menopause is the occasion to assess individual risks, notably vascular and of fractures, taking into account the clinical risk factors and measurement of bone density.
Bone Density↗
How progestins influence the cardiovascular effect of hormone replacement therapy.
Hormone replacement therapy aims to protect against osteoporosis and alleviate fastidious menopausal symptoms such as hot flushes, depression, sleep disturbances and vaginal dryness. In view of the acknowledgement of estrogen deficiency as a major trigger for the acceleration of cardiovascular risk after menopause, hormone replacement therapy may also be proposed as a substantial beneficial cardioprotective agent. The effects of progestins on lipoprotein profile and vasomotor tone are dependent on the chemical structure and the scheme of administration of progestins, with androgenic progestins and cyclical therapy having a potential detrimental effect. Prospective primary and secondary prevention studies, however, suggest that the adjunct of non-androgenic progestins to estrogen therapy is at least as effective as estrogen replacement therapy in reducing cardiovascular mortality and morbidity. Data from recent randomized secondary prevention studies have to be viewed with caution.
Animals↗
Clinical evidence supporting the rationale for constant oestrogen, intermittent progestogen hormone replacement therapy.
Hormone replacement therapy (HRT) effectively relieves vasomotor and other symptoms associated with menopause, yet is underutilised by the majority of menopausal women. Current HRT regimens combine continuous oestrogen with continuous or sequential progestogen in order to achieve the beneficial effects of oestrogen while avoiding the potential for increased risk of endometrial cancer. Uterine bleeding and other adverse progestogenic effects are major reasons for patient noncompliance and early discontinuation of combination HRT, which can ultimately limit the achievement of long-term oestrogenic benefits. A novel constant 17beta-oestradiol, intermittent norgestimate regimen has been developed based on theoretical hormone receptor dynamics in an attempt to minimise the hormonal doses needed, thereby potentially reducing the occurrence of adverse effects associated with higher oestrogen and progestogen doses. Clinical trial data with this novel low-dose HRT regimen demonstrate effective relief of vasomotor symptoms in postmenopausal women, acceptable bleeding rates, no endometrial hyperplasia, beneficial effects on lipids, and excellent tolerability. This regimen has the potential to increase long-term use resulting in important clinical benefits.
Animals↗
The relative effects of progesterone and progestins in hormone replacement therapy.
Hormone replacement therapy (HRT) was initially given to protect women against osteoporosis and alleviate menopausal symptoms, such as hot flashes, depression, sleep disturbances, and vaginal dryness. In view of the understanding of oestrogen deficiency as a major trigger for the acceleration of cardiovascular risk after menopause, HRT may also be proposed as a substantial beneficial cardioprotective agent. Progestins, which may be added to oestrogen in combined HRT to reduce the risk of uterine malignancy, have a number of potential adverse effects on the cardiovascular system which could even attenuate the benefit of unopposed oestrogen replacement therapy in post-menopausal women.
Animals↗
[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.
Adolescent↗
The pharmacoeconomics of hormone replacement therapy.
Hormone replacement therapy (HRT) is a highly cost-effective treatment for symptoms of the menopause such as hot flushes (flashes). A number of economic evaluations have indicated that it may also be a cost-effective therapy for the prevention of cardiovascular disease and osteoporosis. However, these evaluations are based on the premise that HRT will reduce cardiovascular disease by 30 to 50%. Recent evidence casts doubt on its effectiveness at preventing cardiovascular disease, certainly as a secondary preventive therapy. Furthermore, HRT is likely to increase the incidence of breast cancer. If the effect of HRT on the cardiovascular system is slight or nonexistent, but its effect on breast cancer is modest or strong, then HRT is unlikely to be a cost-effective treatment for asymptomatic women at low risk of osteoporosis. However, the unwanted effects of HRT on the breast may be significantly reduced by targeting therapy to those women with low bone mass and who have other risk factors for fracture. Such a strategy is likely to be more cost effective than a strategy which allows asymptomatic women with low fracture risk to take HRT in the long term. As selective estrogen receptor modulators (SERMs) aggravate menopausal symptoms they are not likely to be an alternative for most perimenopausal women. Therefore, SERMs are more likely to be a competitor to existing and forthcoming bisphosphonates rather than HRT.
Cost-Benefit Analysis↗
Thrombotic variables and risk of idiopathic venous thromboembolism in women aged 45-64 years. Relationships to hormone replacement therapy.
Hormone replacement therapy (HRT) has been shown to increase the relative risk of idiopathic venous thromboembolism (VTE) about threefold in several observational studies and one randomised controlled trial. Whether or not this relative risk is higher in women with underlying thrombophilia phenotypes, such as activated protein C (APC) resistance, is unknown. We therefore restudied the participants in a case-control study of the relationship between the use of HRT and the occurrence of idiopathic VTE in women aged 45-64 years. After protocol exclusions, 66 of the cases in the original study and 163 of the controls were studied. Twenty haematological variables relevant to risk of VTE were analysed, including thrombotic states defined from the literature. The relative risk of VTE showed significant associations with APC resistance (OR 4.06; 95% CI 1.62, 10.21); low antithrombin (3.33; 1.15, 9.65) or protein C (2.93; 1.06, 8.14); and high coagulation factor IX (2.34; 1.26, 4.35), or fibrin D-dimer (3.84; 1.99, 7.42). HRT use increased the risk of VTE in women without any of these thrombotic states (OR 4.09; 95% CI 1.26, 13.30). A similar effect of HRT use on the relative risk of VTE was also found in women with prothrombotic states. Thus for example, the combination of HRT use and APC resistance increased the risk of VTE about 13-fold compared with women of similar age without either APC resistance or HRT use (OR 13.27; 95% CI 4.30, 40.97). We conclude that the combination of HRT use and thrombophilias (especially if multiple) increases the relative risk of VTE substantially; hence women known to have thrombophilias (especially if multiple) should be counselled about this increased risk prior to prescription of HRT. However, HRT increases the risk of VTE about fourfold even in women without any thrombotic abnormalities: possible causes are discussed.
Activated Protein C Resistance↗
A decision tree for the use of estrogen replacement therapy or hormone replacement therapy in postmenopausal women: consensus opinion of The North American Menopause Society.
OBJECTIVE: Menopause is associated with physiologic changes that may have negative effects on quality of life in some women and/or that may increase morbidity and mortality secondary to osteoporosis and/or coronary heart disease. Estrogen replacement therapy (ERT) and combined estrogen/progestogen therapy (hormone replacement therapy [HRT]) play an important role in reducing these negative effects. The North American Menopause Society (NAMS) sought to develop treatment algorithms that could assist the clinician in deciding whether to recommend ERT/HRT to postmenopausal women. DESIGN: NAMS held a closed conference of experts to develop a decision tree that outlined the rational use of ERT/HRT in postmenopausal women on the basis of risks versus benefits. The proceedings of the conference were used to assist the NAMS Board of Trustees in developing this consensus opinion of the Society. RESULTS: On the basis of the conference proceedings, NAMS developed three algorithms for the clinician to use as a tool in deciding whether to recommend ERT/HRT to a woman who is postmenopausal: (1) menopause-related symptoms, (2) cardiovascular risk, and (3) osteoporosis risk. CONCLUSIONS: The goal of ERT/HRT is to enhance women's quality of life as well as to reduce the risks of death and disability associated with osteoporosis and coronary heart disease. The decision to initiate ERT/HRT must be individualized according to each woman's needs. This decision tree for ERT/HRT presents a rational approach to decision making on the basis of the principles of care; details of specific therapeutic interventions will change as data from clinical trials are presented.
Algorithms↗
Hormone replacement therapy, hormone levels, and lipoprotein cholesterol concentrations in elderly women.
OBJECTIVE: Our purpose was to assess the relationships of lipid and lipoprotein cholesterol levels to hormone replacement therapy and hormone levels in elderly women. STUDY DESIGN: A sample of 292 postmenopausal women 55 to 99 years old (mean 76 years) was drawn from Leisure World Laguna Hills, California, an upper-middle-class, white independent-living population. We compared 84 women receiving unopposed estrogen replacement therapy and 38 women taking combination hormone replacement therapy with 170 women who had never used hormone replacement therapy. Nonparametric tests for differences in lipid and lipoprotein cholesterol levels among groups and multiple stepwise regression models were used. RESULTS: Estrogen users (with and without progestin) had lower total and low-density lipoprotein cholesterol and higher high-density lipoprotein and high-density lipoprotein subfraction types 2, 2a, and 2b cholesterol levels. High density lipoprotein type 3 subfractions were lower in combination hormone replacement therapy users but higher in unopposed estrogen users relative to nonusers. The conjugated equine estrogen dose was negatively correlated with total (p = 0.0009) and low-density lipoprotein cholesterol (p <0.0001) levels and positively correlated to high-density lipoprotein cholesterol (p = 0.002) and its subfractions. The medroxyprogesterone acetate dose showed no consistent effect on cholesterol levels. CONCLUSION: The associations found here reaffirm the significant role of estrogen replacement therapy on lipid and lipoprotein cholesterol levels and provide no evidence of a reduction in the beneficial effect of estrogen with the addition of a progestational agent to the replacement regimen.
Aged↗
Educating patients about the benefits and drawbacks of hormone replacement therapy.
Hormone replacement therapy (HRT) influences many aspects of health: climacteric symptoms, osteoporosis, cardiovascular disease, breast and endometrial cancer, thrombosis and emboli, and Alzheimer's disease. A decision to use HRT may depend on a woman's individual views of the menopausal transition, the postmenopause and its consequences. It is therefore useful that the health provider inquiries about and discusses these issues in a cultural and family context. Health providers and patients should be thoroughly informed about the symptoms associated with hormonal deprivation, the associated risks of osteoporosis and cardiovascular disease, and the potential of HRT to prevent these afflictions. Recent studies suggest that HRT might be particularly beneficial in women who have an increased risk for cardiovascular disease (because of left ventricular hypertrophy, diabetes mellitus, hypertension or hypercholesterolaemia, or because they smoke) or osteoporosis. In women who are undecided about HRT, a low bone mineral density measurement might help convince them to start using, or to continue using, HRT. There is also a need to discuss with the patient the effect of HRT on cancer risk. In most instances, women can be reassured about the risk of endometrial cancer. The risk of breast cancer should be carefully considered and discussed with each patient before beginning HRT. In most cases, HRT should not be withheld because of fears about breast cancer, because the protective effects of HRT against cardiovascular disease and osteoporosis outweigh the possible increased risk of breast cancer. When HRT is prescribed, individual regiments should be discussed with the patient, who must be warned of the possible adverse effects. In older women, HRT can be started at half the normal dosage and tolerability assessed before increasing the dosage further.
Age Factors↗
Biochemical markers of bone turnover to monitor the bone response to postmenopausal hormone replacement therapy.
Hormone replacement therapy (HRT) prevents postmenopausal bone loss, and is therefore increasingly prescribed to prevent the development of postmenopausal osteoporosis. Because of individual differences in the response to HRT as well as problems with compliance, it has been debated how the skeletal response to HRT should be monitored. When estrogen production decreases at the menopause, a number of biochemical markers of bone turnover increase considerably in the order of 50%-100% from baseline. When HRT is instituted, the markers decrease again within the following 3-6 months. In the present prospective study we investigated whether the determination of biochemical markers of bone turnover may be useful for monitoring the skeletal effect of HRT. Seventy-six early postmenopausal women received HRT and 43 received placebo. The treatment period was 24 months and the women were followed with repeated bone mass measurements (every 3 months) which allowed calculation of the bone loss. Serum and urine samples were collected at 3, 6, 12 and 24 months. The placebo group lost a significant amount of bone mineral density in both the forearm and the spine (p < 0.001), whereas the HRT group did not. There was, however, a relatively large overlap of values between the HRT and placebo groups, especially in the spine. After 3 months' treatment the correlation between the changes in the markers and the bone loss was r = 0.59, and this value increased to r = 0.66 at 6 months and r = 0.76 and r = 0.77 at 12 and 24 months, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Biomarkers↗
Hormone replacement therapy.
Hormone replacement therapy is increasingly being used for purposes unrelated to the alleviation of menopausal symptoms, such as the prevention of osteoporosis and cardiovascular disease. Clinical trials, however, suggest that the one drug/many purposes concept may be too optimistic. The availability of new estrogen-like compounds and the discovery of a second estrogen receptor have opened new possibilities for more specific drug development.
Animals↗
Changes of hemostatic variables during hormone replacement therapy.
Hormone replacement therapy (HRT) is accompanied by many changes in the hemostatic system. Because several individual hemostatic variables have been suspected to be reasonable indicators of the hemostatic balance and because this balance is thought to play an important role in the pathogenesis of several diseases, careful examination of the changes in this system induced by HRT could be helpful, first to improve HRT and second to improve our understanding of mechanisms of cardiovascular disease. The effects of (several forms of) HRT on individual hemostatic variables are discussed in this article. The pattern that emerges is that HRT stimulates coagulation, inhibits anticoagulation, and stimulates fibrinolysis (partly by inhibition of fibrinolysis). There are, however, few data that give clear insight into the effects of HRT on hemostatic variables. Controlled randomized clinical studies are needed to evaluate further the effects of HRT on the hemostatic system, to understand the interplay between inflammation and coagulation (both pathways being affected by HRT), and to understand how HRT-associated changes are affected by differences in genetic background.
Blood Coagulation Factor Inhibitors↗