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This article discusses the use of hormone replacement therapy (HRT) in postmenopausal women who have previously had a myocardial infarction (MI). The article explains that estrogen, the main component of HRT, has benefits for arterial health, including improving vascular function and reducing atheroma formation. Studies have shown that when HRT is initiated in women below the age of 60 or within 10 years of menopause, it can reduce the progression of atherosclerosis and coronary events. The article also addresses the use of HRT in women with existing arterial disease and suggests that low-dose estrogen, preferably non-oral, combined with a non-androgenic progestogen, may be safe for women who have had an MI. The article concludes by providing practice points for clinicians, including the importance of appropriate dosing, the choice of progestogen, the route of administration, and the potential benefits of co-administering a statin. [Extracted from the article]

Abstract: Objectives: Guidelines recommend using the lowest effective dose of oestrogen for the management of vasomotor symptoms in postmenopausal women. The primary aim of this double-blind, multi-centre, randomised study was to assess the efficacy of oral ultra-low dose continuous combined hormone replacement therapy with 17β-oestradiol and dydrogesterone. Study design: 313 women with ≥50 moderate to severe hot flushes during the previous week were randomised to 0.5mg 17β-oestradiol/2.5mg dydrogesterone (E 0.5mg/D 2.5mg), 1mg 17β-oestradiol/5mg dydrogesterone (E 1mg/D 5mg) or placebo for 13 weeks. The placebo group then switched to E 0.5mg/D 2.5mg for a further 39 weeks, whilst the other groups continued on the same treatment. Results: After 13 weeks, the reduction in the number of moderate to severe hot flushes/day in the E 0.5mg/D 2.5mg group was greater than in the placebo group (−6.4 vs. −4.9, p <0.001) and comparable to that in the 1/5mg group (−6.3). E 0.5mg/D 2.5mg and E 1mg/D 5mg significantly improved the total Menopause Rating Scale score. The number of bleeding/spotting days was lower with E 0.5mg/D 2.5mg than with E 1mg/D 5mg. The overall amenorrhoea rate with E 0.5mg/D 2.5mg was 81%; this increased to 91% in months 10–12. Conclusions: Continuous combined 0.5mg 17β-oestradiol and 2.5mg dydrogesterone was effective in alleviating vasomotor symptoms and improving quality of life, and was associated with a high amenorrhoea rate and a good tolerability profile. [ABSTRACT FROM AUTHOR]

The article provides information on the British National Institute for Health and Care Excellence (NICE) guidelines for the diagnosis and management of menopause, focusing on the long-term benefits and risks of hormone therapy (HRT) and its association with increased risks of osteoporosis.

The article provides information on the British National Institute for Health and Care Excellence (NICE) guidelines for the diagnosis and management of menopause, focusing on the long-term benefits and risks of hormone therapy (HRT) and its association with increased risks of cardiovascular disease (CVD).

Abstract: Osteoporosis is a common condition in postmenopausal women and is associated with significant healthcare costs, morbidity and mortality. It is clear that long-term hormone replacement therapy (HRT) has a role to play in preventing osteoporosis by increasing bone mineral density and reducing fracture rate. It is important that these benefits, as well as those on climacteric symptoms, quality of life, colorectal carcinoma and cognition, are not underestimated in the face of the postulated risks with regard to breast cancer and cardiovascular disease. In conclusion, HRT should currently be used only for women with climacteric symptoms or an increased risk of osteoporosis, and it is important that there is an individualised approach to treatment based on each woman''s risk profile. [Copyright &y& Elsevier]

Whether hormone replacement therapy (HRT) is beneficial for coronary heart disease (CHD) is controversial. We hypothesized that continuous combined transdermal HRT may have benefits on CHD risk markers without the potential adverse effects seen with certain other HRT regimens. Sixty apparently healthy postmenopausal women, aged 40–65 years, entered a prospective, double-blind, randomized, placebo-controlled clinical trial; 55 women completed the 6-month study. Women received either transdermal oestradiol 17 β 0·05 mg and norethisterone acetate 0·125 mg daily, or identical placebo. Circulating markers of vascular function and remodelling, forearm blood flow, lipids and lipoproteins, glucose and insulin, and haemostatic safety parameters were measured at baseline and after treatment. Compared with placebo after 6 months, HRT administration resulted in decreased E-selectin ( P < 0·01), and angiotensin-converting-enzyme (ACE; P = 0·05). Cholesterol ( P < 0·05), low-density lipoproteins (LDL; P < 0·05), high-density lipoprotein3 (HDL3; P < 0·05) and apolipoproteins AII ( P < 0·05) and B ( P < 0·05), and fasting insulin ( P < 0·05) also decreased in the HRT group. Factor VII coagulation activity decreased ( P < 0·01) and plasminogen activator inhibitor-1 and fibrin D-dimer increased ( P < 0·05) in the HRT group, whilst prothrombin fragment 1 + 2 ( P < 0·05) decreased, more so in the placebo group. There were no changes in matrix metalloproteinase (MMP)-2, or in LDL particle size. This transdermal HRT had beneficial effects on vascular function and CHD risk markers. [ABSTRACT FROM AUTHOR]

Presents correspondence between medical practitioners as of January 18, 2003. Open letter to World Health Organization Executive Board and candidates for Director General; Long-term effects of hormone replacement therapy; Assessing biomedical science; Angiogenesis with recombinant fibroblast growth factor-2 for claudication; Others.

Controversy still rages about whether hormone replacement therapy (HRT) confers cardiovascular benefit or harm. There is a wealth of biological evidence that estrogen has a beneficial effect, supporting a large body of epidemiological evidence demonstrating reduction in coronary events with HRT. A large randomized placebo-controlled clinical trial of preventive strategies for coronary heart disease (CHD) in postmenopausal women, the Women's Health Initiative (WHI), included HRT arms. The published preliminary findings of this trial showed a significant increase in coronary events, stroke, venous thromboembolism and breast cancer with estrogen--progestogen, leading to the conclusion that HRT was unsafe to use other than for short-term relief of menopausal symptoms. But subsequent publications of the more complete data from WHI have shown no significant increase in CHD, and a tendency to a reduction in those initiating HRT below age 60 years. This is important because other therapeutic strategies for the primary prevention of CHD, such as aspirin and statins, are not of proven benefit in women, in contrast to men. Subsequent WHI findings have not shown a clear increase in breast cancer, and any potential increase from HRT is similar to that seen with many lifestyle factors and other commonly used medications. The preliminary WHI results do not reflect accurately true benefits and risks, and HRT should remain a potential preventive treatment for CHD. [ABSTRACT FROM AUTHOR]

Hormone therapy use has undergone dramatic changes over the past 20 years. Widespread use of hormone therapy in the 1980s and 1990s came to an abrupt halt in the early 2000s after initial findings of the Women's Health Initiative trial were published and the study was terminated. Since then, much has been learned about the characteristics of women most likely to benefit from hormone therapy. There is general agreement that women younger than 60 years or who initiate hormone therapy within 10 years of menopause onset gain short-term benefit in terms of symptomatic relief and long-term benefit in terms of protection from chronic diseases that affect postmenopausal women. Despite accumulating evidence in support of hormone therapy for symptomatic menopausal women, the slow response by the medical community has led to a 'large and unnecessary burden of suffering' by women worldwide. Greater efforts are clearly needed to educate physicians and medical students about the pathophysiology of menopause and the role of hormone therapy in supporting women through the transition. This article provides a brief historical perspective of events that led to the backlash against hormone therapy, explores the current position of guideline groups, and provides practical recommendations to guide first-line management of symptomatic menopausal women. [ABSTRACT FROM AUTHOR]

The article determines the role of hormone replacement therapy (HRT) in addressing coronary heart disease (CHD) in postmenopausal women. Unlike randomized trials that used only one dose of HRT regimen, observational population studies suggest that HRT benefits CHD in women who are at their menopausal stage. The age of initiation of HRT is considered important with the biggest benefit manifested in women undergoing treatment below 60 years of age and within 10 years of onset of menopause. Also noted is a study of low-dose HRT in older women that did not show any cardiovascular harm.

BACKGROUND Previous studies have indicated that there is a trend toward a lower incidence of cardiovascular events in younger menopausal women (aged 50-59 years) who receiving estrogen therapy than in those not who do not receive such therapy. Whether this treatment has an effect on coronary calcification is not known. OBJECTIVES To examine the effect of long-term estrogen therapy on coronary artery calcification in younger postmenopausal women. DESIGN AND INTERVENTION This was a substudy of the randomized, controlled Women's Health Initiative (WHI) trial. The WHI, which commenced in 1993, was conducted at 40 US treatment centers and enrolled postmenopausal women aged 50-79 years at randomization who had undergone a hysterectomy. Patients with a life expectancy of less than 3 years, and those with a malignancy in the previous 10 years, alcoholism, or dementia were excluded. Women enrolled in the WHI study were randomly assigned to receive either 0.625 mg/day oral conjugated equine estrogens or placebo. The trial was scheduled to continue until March 2005, but was terminated early because of concerns over an increased risk of stroke in the estrogen group. Following closure of the main trial, women aged 50-59 years at randomization were invited to participate in the ancillary WHI-Coronary Artery Calcification Study (WHI-CACS). Additional exclusion criteria for this substudy were weight of 300 lbs (136 kg) or more and patient request for no further clinical visits. Women who agreed to participate in WHI-CACS then underwent electron-beam or multidetectorrow CT of the coronary arteries to assess the extent of vessel calcification. OUTCOME MEASURE Coronary artery calcium (Agatston) score, classified as 0 (no calcification), 1-9 (minimal calcification), 10-100 (mild calcification), 101-300 (moderate calcification), and >300 (extensive calcification). RESULTS Of the 2,271 women enrolled in the main WHI study, 1,742 were invited and 1,079 agreed to participate in the substudy. Fifteen women were excluded after CT because of poor-quality scans or previous coronary revascularization procedures. The final study population numbered 1,064 patients, of whom 537 were assigned to receive estrogens and 527 to placebo. The mean treatment period was 7.4 years and CT was performed, on average, 1.3 years after the main WHI trial was closed. Baseline patient characteristics were well matched between the two study groups. The intention-to-treat analysis revealed that women who had received estrogens had significantly lower coronary artery calcification scores than those on placebo (mean 83.1 vs 123.1; P=0.02). This difference was even more significant when the analysis was restricted to women who had 80% adherence to the study drug over 5 years (P<0.002). In the high-adherence group, the multivariate odds ratios for coronary artery calcium scores of >0, ≥10, ≥100 and >300 in women receiving estrogens compared with those on placebo were 0.64 (P=0.01), 0.55 (P<0.001), 0.46 (P=0.001), and 0.39 (P=0.004), respectively. CONCLUSION In the WHI study, postmenopausal women aged 50-59 years treated with long-term estrogen therapy had lower levels of coronary artery calcification than those who received placebo. [ABSTRACT FROM AUTHOR]

Comments on a finding of a clinical trial concerning potential side effects of hormone replacement therapy (HRT). Suggestion that post-menopausal HRT may have benefits, including reductions in coronary heart disease (CHD); Increase in risks for breast cancer, CHD, and stroke which were linked to HRT; Belief that long-term HRT should be given only on an individual basis.

Objectives: Various combinations of estrogens and progestogens are available for menopausal hormone therapy that differ in their efficacy and safety profile. We evaluated the efficacy and long-term safety of low-dose estradiol (0.5 mg) / dydrogesterone (2.5 mg) in subgroups of postmenopausal women with vasomotor symptoms.Analysis: Efficacy analysis was performed on data from 2 previously published studies for subgroups defined by age, duration of menopause, and body mass index at baseline. The primary efficacy variable was the number of moderate to severe hot flushes from baseline to week 13. Long-term safety was evaluated in relation to age and duration of menopause. Safety variables included adverse events to week 52 and change from baseline to endpoint in laboratory and vital sign values.Results: The treatment difference seen in the overall population in favour of low-dose estradiol/dydrogesterone was also observed in the subgroups of patients aged 45 to < 55 years (p < 0.01) and ≥55 years (p < 0.05), with menopause duration of >12 months to <60 months (p < 0.05) and ≥ 60 months (p < 0.005), and with a BMI at baseline of <25 kg/m2 (p < 0.05) and 25 to <30 kg/m2 (p < 0.01). Low-dose estradilol/dydrogesterone was well tolerated across the different subgroups. The incidence of breast-related adverse events was very low. No breast malignancy was reported. Only one adverse endometrial outcome of simple hyperplasia was observed.Conclusion: The results of our analyses confirmed the consistent treatment effect on vasomotor symptoms and the favourable safety profile of 0.5 mg 17β estradiol and 2.5 mg dydrogesterone in different patient subgroups. [ABSTRACT FROM AUTHOR]

Introduction: While the associations of genetic, reproductive and environmental factors with the timing of natural menopause have been extensively investigated, few epidemiological studies have specifically examined their association with premature (<40 years) or early natural menopause (40-45 years).Aim: The aim of this position statement is to provide evidence on the predictors of premature and early natural menopause, as well as recommendations for the management of premature and early menopause and future research.Materials and Methods: Literature review and consensus of expert opinion.Results and Conclusions: Strong genetic predictors of premature and early menopause include a family history of premature or early menopause, being a child of a multiple pregnancy and some specific genetic variants. Women with early menarche and nulliparity or low parity are also at a higher risk of experiencing premature or early menopause. Cigarette smoking (with a strong dose-response effect) and being underweight have been consistently associated with premature and early menopause. Current guidelines for the management of premature and early menopause mainly focus on early initiation of hormone therapy (HT) and continued treatment until the woman reaches the average age at menopause (50-52 years). We suggest that clinicians and health professionals consider the age at menopause of the relevant region or ethnic group as part of the assessment for the timing of HT cessation. In addition, there should be early monitoring of women with a family history of early menopause, who are a child of a multiple pregnancy, or who have had early menarche (especially those who have had no children). As part of preventive health strategies, women should be encouraged to quit smoking (preferably before the age of 30 years) and maintain optimal weight in order to reduce their risk of premature or early menopause. [ABSTRACT FROM AUTHOR]

This position statement from the European Menopause and Andropause Society (EMAS) provides a care pathway for the maintenance of women's health during and after the menopause. It is designed for use by all those involved in women's health. It covers assessment, screening for diseases in later life, treatment and follow-up. Strategies need to be optimised to maintain postreproductive health, in part because of increased longevity. They encompass optimising diet and lifestyle, menopausal hormone therapy and non-estrogen-based treatment options for climacteric symptoms and skeletal conservation, personalised to individual needs. [ABSTRACT FROM AUTHOR]

Abstract: In women experiencing distressing climacteric symptoms during the peri- and postmenopause there is conclusive evidence from abundant randomised controlled trials that systemic hormone replacement therapy (HRT) of any type affords symptom relief, with no alternative treatment producing similar effect. Though this evidence is accumulating, the question of how to provide best clinical practice in an attempt to both alleviate the menopausal symptoms and prevent the more long-term postmenopausal degenerative diseases is still under debate. When providing climacteric medicine, the dose and regimen of HRT needs to be individualised based on the principle of choosing the lowest appropriate dose in relation to severity of symptoms and on the menopausal age. However, few long-term data on different HRT formulations exist in symptomatic women, which also account for baseline risk of cardiovascular disease (CVD), breast cancer and osteoporosis. In most cases, an individualized prescription together with life-style management will sustain possibilities for net beneficial effects on climacteric symptoms, quality of life (QoL), sexuality and osteoporosis, with only rare risk of severe adverse effects. With the perspective provided by recent epidemiological findings, not least from the estrogen only arm of the Women''s Health Initiative Study (WHI), European Menopause and Andropause Society (EMAS) supports research activities in symptomatic women with new HRT formulations in order to affect positively the balance of clinical benefit and risk, including specific information on QoL and also account for the traditional differences in treatment modalities between the US and Europe, and the difference in BMI, life-style and diet. In women experiencing an early menopause (&#60;45 year) current data support a specific overall benefit of HRT. At present, more long-term systemic HRT may be considered in women at high risk of osteoporotic fractures, in particular when alternate therapies are either inappropriate or insufficiently effective, as benefits will outweigh any risks. In contrast, urogenital symptoms may be addressed efficiently and safely with long-term local estrogen therapy. [Copyright &y& Elsevier]