Attitudes of women toward hormone therapy and prevention of heart disease

Menopausal hormone therapy informed consent

Breast cancer, menopause, and long-term survivorship: critical issues for the 21st century

Menopausal hormone therapy: summary of a scientific workshop.

Background In an integrated overview of the benefits and risks of menopausal hormone therapy (HT), the Women's Health Initiative (WHI) investigators have claimed that their ‘findings … do not support use of this therapy for chronic disease prevention’. In an accompanying editorial, it was claimed that ‘the WHI overturned medical dogma regarding menopausal [HT]‘.Objectives To evaluate those claims.Methods Epidemiological criteria of causation were applied to the evidence.Results A ‘global index’ purporting to summarize the overall benefit versus the risk of HT was not valid, and it was biased. For coronary heart disease, an increased risk in users of estrogen plus progestogen (E + P), previously reported by the WHI, was not confirmed. The WHI study did not establish that E+ P increases the risk of breast cancer; the findings suggest that unopposed estrogen therapy (ET) does not increase the risk, and may even reduce it. The findings for stroke and pulmonary embolism were compatible with an increased risk, and among E+ P users there were credible reductions in the risk of colorectal and endometrial cancer. For E+ P and ET users, there were credible reductions in the risk of hip fracture. Under ‘worst case’ and ‘best case’ assumptions, the changes in the incidence of the outcomes attributable to HT were minor.Conclusions Over-interpretation and misrepresentation of the WHI findings have damaged the health and well-being of menopausal women by convincing them and their health professionals that the risks of HT outweigh the benefits.

Current recommendations: what is the clinician to do?

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Menopausal hormone therapy—Benefits, adverse reactions, concerns and information sources in 2009

Understanding physicians’ attitudes towards hormone therapy

The Women's Health Initiative (WHI) trial was a major contribution to the understanding of the risks and benefits of hormone therapy (HT) in postmenopausal women. Further analyses of the results of the WHI trial and a seminal review by Kuhl and Stevenson have put a new perspective on the benefits and risks of HT.1 It is suggested that (A) Breast cancer (i) Body mass and prior HT are important factors in determining the risk of breast cancer associated with HT. (ii) The increased risk of breast cancer with CEE+MPA in the WHI trial is an artefact due to the low incidence of breast cancer in the placebo group of women. (iii) The, so far, unexplained reduction in risk of breast cancer with CEE only in women age 50-59 could be due to the estrogen-induced reduction in insulin levels in the women who were overweight or obese, the majority of whom probably had the “metabolic syndrome” and hyperinsulinaemia. (B) Coronary Heart Disease (CHD) (i) CEE only in younger healthy postmenopausal women decreases the incidence of CHD but CEE+MPA in older women increases the incidence of CHD. (ii) Addition of MPA to CEE in postmenopausal women increases the risk of CHD possibly due to an MPAinduced upregulation of thrombin receptors in the coronary arteries. (iii) The effect of HT on the incidence of CHD is determined by age and by time since menopause on initiating HT. It is hypothesised that “HT in younger postmenopausal women prevents atherosclerosis and reduces the risk of cardiovascular disease BUT in older postmenopausal women increases the risk of thrombosis and inflammation and of cardiovascular disease in women with atherosclerotic plaques”. (C)Stroke and Total Mortality (i) The increased incidence of stroke in women over age 60 with both the CEE+MPA and CEE only arms of theWHI trial is the main reason for caution in the use of HT in older postmenopausal women (ii) The reduction in total mortality in women under 60 with both CEE+MPA and CEE only is an important new finding and requires further investigation. (iii) The significant reduction in total mortality provides reassurance, if any is needed, of the safety and benefits of HT in younger postmenopausal womenO & G Forum Vol. 17 (4) 2007: pp. 105-110

ER+/PR+/HER2‐ breast cancers are frequently associated with good outcomes, but some patients experience disease progression/recurrence. We examined disease relapse and relapse‐free survival (RFS) as measures of response to chemotherapy (Chemo), hormone therapy (HT), and Chemo+HT among 182 ER+/PR+/HER2‐ breast cancers (with known molecular subtype) that differentially express a 583‐gene estrogen response signature (ERS). 25 patients received Chemo, 13 received HT, 20 received Chemo+HT, and 124 patients received no adjuvant therapy (surgery only). Overall, ERS+ ER+/PR+/HER2‐ breast cancers have better RFS (62/142, 43% relapse irrespective of therapy) versus ERS‐ ER+/PR+/HER2‐ breast cancers (26/39, 67% relapse irrespective of therapy). Regardless of ERS status, 29/58 (50%) treated patients relapse and 60/124 (48%) untreated patients relapse. However, response to therapy varies according to ERS status among treated patients. ERS+ ER+/PR+/HER2‐ breast cancers show benefit of HT or Chemo+HT – 45/96 (47%) untreated relapse and 10/19 (52%) Chemo relapse versus 3/9 (33%) HT relapse and 4/18 (22%) Chemo+HT relapse. ERS‐ ER+/PR+/HER2‐ breast cancers do not show benefit of Chemo, HT, or Chemo+HT – 15/28 (54%) untreated relapse and 11/11 (100%) treated relapse (irrespective of adjuvant modality). These results suggest that there is value in knowing ERS when treating ER+/PR+/HER2‐ breast cancers.

Evaluating the benefits and risks of postmenopausal hormone therapy

The profound disparities between the largely positive basic science findings of gonadal steroid action in brain and the adverse outcomes of recent hormone therapy clinical trials in women who are either aged postmenopausal or postmenopausal with Alzheimer's disease have led to an intense reassessment of gonadal hormone action and the model systems used in basic and clinical science. The power of model systems is their predictive validity for a target population--in this case, menopausal women considering the health benefits and risks of hormone therapy. Analysis of the model systems used across the basic to clinical research continuum separate into two broad classes: those that use prevention interventions in healthy organisms and those that use hormone interventions in organisms with compromised neurological function. Basic science analyses that led to elucidation of the neurotrophic and neuroprotective effects of estrogen and the underlying mechanisms of action typically used a prevention-based experimental paradigm. This paradigm relies on healthy neurons/brains/animals/humans as the starting foundation followed by exposure to estrogen/hormone followed by exposure to neurodegenerative insult. The prevention paradigm in basic science analyses parallels the analyses of Sherwin and colleagues (Psychoneuroendocrinology 13: 345-357, 1988), who investigated the cognitive impact of estrogen therapy in women with surgical- or pharmacological-induced menopause. Observational retrospective and prospective studies are also consistent with the healthy cell bias of estrogen action and a prevention paradigm of estrogen or hormone therapy intervention. For the most part, the epidemiological observational data indicate reduction in the risk of Alzheimer's disease in women who began estrogen or hormone therapy at the time of the menopause. In contrast, studies that fall within the second class, hormone intervention in organisms with compromised neurological function--that is, a treatment paradigm--exhibit a mixed profile. In a randomized double-blind clinical trial of estrogen therapy in a cohort of women aged 72 or more years and diagnosed with Alzheimer's disease, estrogen therapy resulted in a modest benefit in the short term (2 months) and adverse progression of disease in the long term (12 months). In the Women's Health Initiative Memory Study (WHIMS) cohort of women 65 or more years of age, with no indicators of neurological disease but with variable health status, estrogen and hormone therapy for 5 years increased the risk of developing Alzheimer's disease. These data would suggest that as the continuum of neurological health progresses from healthy to unhealthy, so too do the benefits of estrogen or hormone therapy. If neurons are healthy at the time of estrogen exposure, their response to estrogen is beneficial for both neurological function and survival. In contrast, if neurological health is compromised, estrogen exposure over time exacerbates neurological demise. Based on these and other data, a hypothesis of a healthy cell bias of gonadal hormone action is put forth. The healthy cell bias of estrogen action hypothesis provides a lens through which to assess the disparities in outcomes across the domains of scientific inquiry and to access future applications of estrogen and hormone therapeutic interventions.

The objective was to develop an individualized risk-benefit model quantifying the impact of combined use of estrogen and progestogen on chronic diseases. The study population consisted of women, aged 40+, prescribed postmenopausal hormone therapy (HT) in the UK General Practice Research Database (N > 200,000). Individualized risks of fracture, colorectal cancer, diabetes mellitus, myocardial infarction, deep venous thrombosis/pulmonary embolism, breast cancer, and stroke were estimated using Cox regression. Relative rates from the Women's Health Initiative trial were used to estimate attributable risks (ie, excess risks) in a risk-benefit simulation model. Risks and benefits increased with age and length of HT use. HT use for 5 years initiated at age 45 increased the absolute risk of myocardial infarction by 0.04% and breast cancer by 0.3% and reduced the risk of hip fracture by 0.03%. Comparably, 5-year HT use started at age 75 led to increases in the risks of myocardial infarction and breast cancer (+0.4% and +0.2%, respectively) and reduced that of hip fracture (-0.9%). There was considerable heterogeneity in the risks and benefits of HT. In most of the younger HT users, the frequency of risks exceeded that of the benefits, although the absolute excess risks were small. In HT users aged 70+, 62.4% experienced more benefits than risks, whereas 37.6% experienced more risks than benefits. The frequency of beneficial and adverse effects of HT on chronic diseases was low in younger women, whereas the ratio of these risks and benefits varied substantially among the older users. However, the study could not asses the effects of HT on menopausal symptoms and quality of life, benefits more likely to be observed among younger women.

Breast cancer is the most common invasive cancer diagnosed in women. Of every 8 women, 1 woman is diagnosed with breast cancer in her lifetime. In 2013, more than 230 000 women were diagnosed with breast cancer in the United States alone, resulting in nearly 40 000 deaths. Breast cancer can also occur in men, although the incidence is much lower, with a total of 2240 men diagnosed in 2013 (accounting for less than 1% of all breast cancers). Over the past 2 decades, death resulting from breast cancer has been declining each year. This decrease in mortality is due in part to improvements in cancer treatment. These treatments have come about as a result of collaborations among physicians in various specialties. These physicians include medical oncologists (who give systemic treatments like chemotherapy and hormonal therapy), surgeons (who perform surgery such as mastectomy and lumpectomy), and radiation oncologists (who treat patients with radiation therapy). Radiation therapy, in particular, has increasingly become an important part of management of most patients with breast cancer. Radiation therapy has been demonstrated not only to prevent recurrence of cancer in the breast or chest wall area but also to improve long-term survival in women. In addition, radiation therapy allows women to undergo a less radical form of surgery in which the breast tissue is conserved, thus improving body image for breast cancer survivors without compromising survival. As a result of this progress in treatment and improved detection of early breast cancer, in 2012, there were nearly 3 million breast cancer survivors in the United States alone, a number that will increase in the coming years. Women who survive breast cancer may face many health challenges, but the number 1 cause of death in breast cancer survivors (and, in fact, all women) remains heart disease. Unfortunately, although systemic …

A decision aid for women considering hormone therapy after menopause: decision support framework and evaluation