The observational studies of hormone users are compromised by systematic biases that lead to an overestimation of benefit and an underestimation of risk. Studies of mechanism could support either benefit or harm. The results of clinical trials of oral hormone therapy in women with existing coronary heart disease (CHD) have been uniformly disappointing. The largest trial found an early increased risk for CHD and for venous thromboembolism. Postmenopausal hormone therapy should not be considered for CHD prevention until methods for excluding high-risk women have been established, and until the results of the long-term trials have shown benefit. There is a need for clinical trials of nonoral estrogens.

Postmenopausal hormone replacement therapy (HRT) with oral oestrogen was predicted to reduce coronary heart disease (CHD) risk by 50%. Randomized controlled trials show no such benefit, however, pointing instead to an initial increase in CHD events. Although the cardiovascular effects of transdermal HRT are largely unknown, improvements in arterial function are maintained when oestrogen is administered transdermally. Transdermal HRT also avoids the increased plasma levels of C-reactive protein (CRP) that are seen with oral HRT. However, the clinical significance of this general reduction in hepatic over-synthesis of plasma proteins is difficult to assess. Nevertheless, the available evidence on transdermal HRT appears to justify a formal clinical trial.

Background It is known that use of hormone replacement therapy (HRT) by postmenopausal women increases the risk of breast cancer. Method In this study, oestrogen receptor (ER)-α expression is examined using standard immunoperoxidase technique. Results Normal breast samples of 11 Australian postmenopausal women have been included in the ER-α study; the result showed a strong correlation (r2 = 0.80) between ER-α expression in normal breast epithelial cells and body mass index (BMI) in normal women who currently use HRT. Conclusion This finding confirms that the possibility of increased risk of breast cancer associated with increased ER-α expression in normal breast epithelial cells, in turn associated with high BMI and the use of HRT.

Background Hormone replacement therapy (HRT) is often seen as the treatment of choice for preventing fractures in women. We undertook a recent meta-analysis of randomised trials which suggested that HRT reduced non-vertebral fractures by 30%. In this analysis we extend that analysis to vertebral fractures. Methods We searched the main electronic databases until the end of August 2001. We sought all randomised controlled trials (RCTs) of HRT where women had been randomised to at least 12 months of HRT or to no HRT. Results We found 13 RCTs. Overall there was a 33% reduction in vertebral factures (95% confidence interval (CI) 45% to 98%). Conclusions This review and meta-analysis showed a significant reduction in vertebral fractures associated with HRT use.

Background The objective of this study was to study the association of early age at menopause with pulse pressure (PP), a marker of arterial stiffness, and PP change. Methods The effect of natural menopause was studied in 2484 women from the Atherosclerosis Risk in Communities (ARIC) Study who had not used hormone replacement therapy and who had not had a hysterectomy. The cross-sectional association of age with PP was evaluated in the entire cohort. The cross-sectional association of recalled age at menopause was evaluated in the 1688 women who were postmenopausal at baseline. PP change over 6 years was assessed in relation to menopausal age separately in women who were postmenopausal at baseline and in those whose menopause occurred during the 6-year interval. Results Chronological age was strongly and positively associated with PP in cross-sectional analyses, but not independently associated with PP change. While menopausal age was not associated cross-sectionally with PP, early age at menopause (age<45) was significantly and independently associated with a slightly larger increase in PP (8.4, 95% CI 7.0–9.8) than later menopause (6.5, 95% CI 5.8;7.2). However, among normotensive women the difference was not statistically significant (p = 0.07, 6.1 vs 4.7). Conclusions Early age at menopause may be related to a greater increase in arterial stiffness, but the effect appears to be small and further evidence is needed.

Background Differences in the management of coronary artery disease between men and women have been reported in the literature. There are few studies of potential inequalities of treatment that arise from a primary care context. This study investigated the existence of such inequalities in the medical management of post myocardial infarction in older patients. Methods A comprehensive chart audit was conducted of 142 men and 81 women in an academic primary care practice. Variables were extracted on demographic variables, cardiovascular risk factors, medical and non-medical management of myocardial infarction. Results Women were older than men. The groups were comparable in terms of cardiac risk factors. A statistically significant difference (14.6%: 95% CI 0.048–28.7 p = 0.047) was found between men and women for the prescription of lipid lowering medications. 25.3% (p = 0.0005, CI 11.45, 39.65) more men than women had undergone angiography, and 14.4 % (p = 0.029, CI 2.2, 26.6) more men than women had undergone coronary artery bypass graft surgery. Conclusion Women are less likely than men to receive lipid-lowering medication which may indicate less aggressive secondary prevention in the primary care setting.

During the second part of the twentieth century, research advances caused a substantial decline in the rate of coronary heart disease. The decline lasted from the mid-1960s until the early 1990s and occurred primarily in Western countries. However, an unfavourable trend in coronary heart disease related mortality has gradually developed during the 1990s, with cardiovascular diseases anticipated to remain the main cause of overall mortality for the foreseeable future. The present paper aims at analyzing the current status of the main determinants of population-wide coronary heart disease prevention.

Surrogate outcomes are frequently used in cardiovascular disease research. A concern is that changes in surrogate markers may not reflect changes in disease outcomes. Two recent clinical trials (Heart and Estrogen/Progestin Replacement Study [HERS], and the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial [ALLHAT]) underscore this problem since their results contradicted what was expected based on the surrogate outcomes. The current regulatory policy to allow new therapies to be introduced onto the market based solely on surrogate outcomes may need to be reviewed.