Hormone Replacement Therapy for Cardiovascular Prevention: Hope or Hype?

Estrogen replacement therapy in patients with early breast cancer

To use magnetic resonance (MR) imaging to evaluate tissue perfusion in the normal breast parenchyma of postmenopausal women with current or recent hormone replacement therapy (HRT). The study was approved by the institutional subcommittee on human studies, and informed consent was obtained from all patients prior to MR imaging. Sixty postmenopausal women (age range, 44-77 years) were grouped according to HRT received: estrogen replacement therapy (ERT) (n = 13), combined (estrogen and progesterone) replacement therapy (CRT) (n = 16), selective estrogen receptor modulator (SERM) therapy (n = 8), and no (hormone replacement) therapy (NT) (n = 23). MR imaging with a 1.5-T magnet was performed by using gradient-echo and dynamic contrast material-enhanced echo-planar pulse sequences before and after gadopentetate dimeglumine injection. Precontrast T1 relaxation times were measured, after which extraction-flow product (EFP) maps were calculated with a multicompartmental model. Analysis of variance was performed. Age did not significantly differ between the groups (P > .3). Women receiving ERT or CRT at the time of MR imaging had higher EFP values (7.3 mL . 100 g(-1) . min(-1)+/- 2.6 and 7.1 mL . 100 g(-1) . min(-1)+/- 3.8, respectively) than did women receiving NT (4.4 mL . 100 g(-1) . min(-1)+/- 2.1) (P = .012 and P = .008, respectively) or SERM therapy (3.9 mL . 100 g(-1) . min(-1)+/- 1.1) (P = .015 and P = .013, respectively). Women who ended ERT or CRT 1-47 months before MR examination had lower EFP values than did women with current ERT or CRT and had higher EFP values than did women receiving NT or SERM therapy (6.2 mL . 100 g(-1) . min(-1)+/- 2.4 and 5.9 mL . 100 g(-1) . min(-1)+/- 3.8, respectively), but the observed differences were not significant (P > .1). Differences in T1 between all groups were not significant (P > .5). Higher breast tissue perfusion is observed in postmenopausal women receiving HRT.

A quality assessment and systematic review of clinical practice guidelines on hormone replacement therapy for menopause using the AGREE II instrument

In 1993, individuals with a hereditary predisposition to venous thromboembolism whose plasmas exhibited a poor response to activated protein C (APC) in an activated partial thromboplastin time assay were identified.1 The molecular basis for this laboratory phenotype of resistance to APC was a guanine to adenine mutation at nucleotide 1691 in the factor V gene.2 This results in the replacement of arginine (R) at position 506 by glutamine in the resulting protein, a defect which has been termed factor V Leiden. R506 is the first of three sites at which APC normally cleaves and inactivates procoagulant factor Va. The Q506 substitution causes factor Va to be inactivated approximately l0-fold more slowly than normal, thereby making the cofactor relatively resistant to the anticoagulant action of APC.3 This allows for increased factor Va availability within the prothrombinase complex, thereby enhancing thrombin generation and the development of a hypercoagulable state. See page 1012 Factor V Leiden is the most common inherited risk factor for venous thromboembolism, increasing the risk of venous thrombosis by 4- to 10-fold in heterozygotes and 50- to 100-fold in homozygotes.4,5⇓ Heterozygosity can be identified in 12% to 20% of unselected white patients presenting with venous thrombosis and 40% to 50% of patients with a strong positive family history. Approximately 3% to 7% of normal white patients are heterozygous carriers of factor V Leiden, but the mutation is rare in …

We recently highlighted the current uncertainty surrounding the use of hormone replacement therapy (HRT) in relation to coronary heart disease (CHD).1 As we pointed out in our paper, recent large prospective randomised studies have failed to confirm observations from several large epidemiological surveys suggesting a beneficial effect of HRT in preventing CHD.3 Few arguments had been raised to try to explain the discrepancy, but one was the possible bias in patient selection in that women on HRT might have been healthier, received more health monitoring and taken a greater interest in modifying cardiovascular risks. However, the observations we recently reported did not support such a ‘healthy cohort’ hypothesis, because HRT users appeared to be less likely to undergo investigations such as cervical smears and mammograms.1 As most of the HRT given to patients in epidemiological studies were mainly prescribed and managed by their general practitioners (GP), we hypothesised that this ‘healthy cohort’ effect could perhaps relate more to GPs who are actively involved in HRT/menopause care. To test this hypothesis, we extended our previous survey of HRT use to another general practice in the west of Birmingham, which had a regular menopause clinic. Using the practice computer system, we reviewed notes from 143 HRT users and 131 age-matched non-users (as controls) who were randomly selected from the 619 women aged between 40 and 60 years in the practice population of 6900. There were no significant differences in age, body mass index and the presence of each of the cardiovascular risk factors between the two groups. However, there were significantly fewer Indo-Asian women on HRT, although none of them had any known contraindications for the therapy (Table 1). The main indication for HRT use was the presence of menopausal symptoms, such as hot flushes and genitourinary discomfort (Table 2). Only 3 (2.1%) patients in our study were taking HRT specifically to prevent osteoporosis and none for the prevention of cardiovascular disease. In addition, patients with a known history of cardiovascular disease were not excluded from being prescribed HRT. On the other hand, there were no known contraindications for HRT in 90% of the non-users, although up to 45% had documented menopausal symptoms; the same number of patients had osteoporosis as had HRT users. Interestingly, none of the patients who were offered HRT by their GP but who subsequently refused had a history of CHD. Thus, as in our previous report,1 it appears that cardiovascular risk or cardiovascular prevention was not a factor to be considered by either patients or GPs on whether or not to prescribe HRT. Unlike in our previous report, HRT users in this practice made significantly more visits to their GPs and had regular blood pressure checks, mammograms and lipid profile tests, as well as more frequent cervical smear tests (apart from those who had had a hysterectomy) than non-users (Table 1). HRT users also made more visits to their GP within the previous 12 months (p<0.001). In conclusion, our results are broadly in accordance with our previous report and support the fact that women taking HRT were no healthier in terms of cardiovascular risk than non-users, nor did they seek more cardiovascular preventive care than non-users. However, proponents of the ‘healthy cohort’ hypothesis have suggested that patients on HRT were monitored more closely, so may have biased the results of previous epidemiological case controlled studies. Our extended observations in this general practice, which actively managed postmenopausal women in a menopause clinic, suggest that the ‘healthy cohort’ effect may actually exist, and be GP-initiated. Nevertheless, this does not necessarily mean that women who are monitored more closely are healthier. Pending further data from more prospective randomised controlled trials, the jury is still out regarding the use of HRT for cardiovascular prevention.2

Hormone replacement therapy in postmenopausal women with end-stage renal disease

Changes in Fertility and Hormone Replacement Therapy in Kidney Disease

Retinal Vessel Diameter

To evaluate the effect of hormone replacement therapy (HRT) for menopause on the mechanical properties of the skin in healthy women. A group of 114 women, including 43 nonmenopausal controls, 46 menopausal women with HRT and 25 menopausal women without HRT, participated in the study. Mechanical properties of the skin were measured on the volar forearm using a computerized suction device. University medical center. Research laboratory in bioengineering and biometrology. Computerized measurements of skin deformability and viscoelasticity revealed differences between the three groups of women. A steep increase in skin extensibility was evidenced during the perimenopause in untreated women. HRT appeared to limit the age-related increase in cutaneous extensibility, thereby exerting a preventive effect on skin slackness. No effect of HRT was found on other parameters of skin viscoelasticity. HRT has a beneficial effect on some mechanical properties of skin and thus may slow the progress of intrinsic cutaneous aging.

Cardiovascular News

Menopausal status and hormone replacement therapy (HRT) cause alterations in breast structure which can affect mammographic image quality. Here we present the results of a study to discover the effect of menopausal status and HRT use on breast dose. Women attending routine screening completed questionnaires which included questions regarding menopausal status and HRT use. Details of the radiographic technique factors were recorded, from which the mean glandular dose (MGD) per film for each woman was calculated. MGD values were analysed with regard to the woman's menopausal status and HRT use. The data from 516 women were analysed. Among the women who had never used HRT, women who had not undergone the menopause had a mean MGD of 2.94 mGy per film, whereas post-menopausal women had a lower mean MGD of 2.52 mGy per film: a difference which was found to be highly significant (p = 0.0045). Post-menopausal women who had never used HRT and those who had previously used HRT, but had ceased using it, had identical mean MGDs (2.54 mGy per film), whereas current HRT users had a significantly greater mean MGD (2.89 mGy per film, p = 0.003). Women currently using HRT receive a statistically significantly larger radiation dose from routine breast screening than other women. However, this effect is small and only occurs during the period of HRT use. Women who have ceased using HRT show no difference in MGD compared with women who have never taken HRT.

Oestrogen replacement therapy is associated with a marked reduction in coronary event rates in post-menopausal women. As older age is associated with progressive arterial endothelial damage, a key event in atherosclerosis, we assessed whether hormone replacement therapy (HRT) with oestrogen alone, or oestrogen and progesterone combined, is associated with improved endothelial function in healthy women after the menopause. Using high resolution external vascular ultrasound, brachial artery diameter was measured at rest and in response to reactive hyperaemia, with increased flow causing endothelium-dependent dilatation (flow-mediated dilatation). We investigated 135 healthy women; 40 were pre-menopausal (mean +/- SD age/26 +/- 6 years, group 1), 40 were post-menopausal and had never taken HRT (aged 58 +/- 3 years; group 2) and 55 were age-matched post-menopausal women who had taken HRT for > or = 2 years, from within 2 years of the menopause (aged 57 +/- 4 years; group 3). In group 3, 40 women were on combined oestrogen and progesterone and 15 on oestrogen-only HRT. In group 2, flow-mediated dilatation was significantly reduced compared with group 1 (4.4 +/- 3.4 vs 9.6 +/- 3.6%, P < 0.001), consistent with a decline in arterial endothelial function after the menopause. In group 3, however, flow-mediated dilatation was significantly better than group 2 (6.2 +/- 3.3 vs 4.4 +/- 3.4%, P = 0.01), suggesting a protective effect of HRT. Flow-mediated dilatation was similar in women taking oestrogen alone and in those on combined HRT (5.5 +/- 2.8 vs 6.5 +/- 3.4%, P = 0.40). Long-term HRT is associated with improved arterial endothelial function in healthy post-menopausal women. This benefit was observed in both the combined hormone replacement and unopposed oestrogen therapy groups. This may explain some of the apparent cardioprotective effect of HRT after the menopause.

An estimated one third of all American and United Kingdom women take hormone therapy. In sharp contrast to these numbers, as many as one half of women diagnosed with breast cancer have taken hormones. Little additional information is available regarding the risk of breast cancer and even less is known about the association between hormone therapy and fibrocystic (FCD) disease or atypia of the breast. Three hundred women between 30 and 50 years of age were enrolled in this study, including 120 taking hormone replacement (HRT) therapy and 180 women who had never taken hormone therapy. These women were divided into four categories including those with normal breast tissue, those with FCD disease, those with cellular atypia, and those with breast cancer. Another group of women were also identified who had breast implants. Using breast enhanced scintigraphy (BEST) imaging, changes in breast tissue were determined and compared according to the use of HRT. Forty percent (122 of 300) had "normal" breasts, of whom 68.8% (84 of 122) did not take HRT. This accounted for 46.7% (84 of 180) of the women not taking hormone therapy, while only 31.7% (38 of 120) of the women taking HRT had normal breasts. This difference was statistically (p.001) significant. There was a greater incidence of breast abnormality in women taking HRT and a lower incidence in pathology among women not taking HRT when cumulatively analyzed for FCD, cellular atypia, and breast cancer. This difference was statistically significant (p.001) for women with breast cancer where 62.5% (10 of 16) were women taking HRT. Although the study was relatively small, it is the first such study to compare a continuum of changes in breast tissue according to the use of HRT. The study suggests that the initial empirical observations regarding higher incidence of HRT among women with breast cancer, may have a relationship to underlying changes in breast tissue that are associated with differences in mitochondrial content and activity. Further investigation is needed.

Hormone Replacement Therapy and Decreased Lung Cancer Survival

Introduction: Cardiovascular disease (CVD) is the leading cause of death in women. Low estrogen levels during menopause are associated with an increased risk of CVD. Therefore, hormone replacement therapy (HRT) can mitigate menopause-related diseases. Vasomotor symptoms affect about 60.0 to 80.0% of postmenopausal women and may have an incidence of 90.0% in perimenopausal women. The main studies in the last 20 years have investigated the effects of estrogen therapy on symptoms and women's health during menopause. Objective: This was to conduct a systematic review to better understand the main findings and discussions of international consensus on hormonal therapies in women regarding cardiovascular events. Methods: The systematic review rules of the PRISMA Platform were followed. The research was carried out from May to June 2025 in Scopus, Embase, PubMed, Science Direct, Scielo, and Google Scholar databases. The quality of the studies was based on the GRADE instrument, and the risk of bias was analyzed according to the Cochrane instrument. Results and Conclusion: A total of 130 articles were found. A total of 39 articles were fully evaluated, and 23 were included and developed in the present systematic review study. Considering the Cochrane tool for risk of bias, the overall assessment resulted in 21 studies at high risk of bias and 25 studies that did not meet the GRADE and AMSTAR-2. It was concluded that hormone replacement therapy is a sex-specific and time-dependent primary cardiovascular disease prevention therapy that concomitantly reduces all-cause mortality as well as other aging-related diseases. Observational studies did not suggest an increased risk of myocardial infarction in postmenopausal women with diabetes prescribed HRT. Lipoprotein, LDL-C, and insulin resistance were lower with hormone therapy, and HDL-C levels were higher with hormone therapy compared to placebo. Thus, hormone therapy in women was shown to be important for improving organic functions and quality of life, as well as showing a bias in reducing cardiovascular events.