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hormone replacement therapy

Hormone Replacement Therapy in the Older Adult

Hormone Replacement Therapy in the Older Adult

Teaser: 


Karin H. Humphries, MBA, DSC, Division of Cardiology, Department of Medicine, University of British Columbia, Vancouver, BC.
Janet McElhaney, MD, Department of Geriatrics, University of British Columbia, Vancouver, BC.

The growth in information about hormone replacement therapy (HRT) over the past few years has been impressive. This review summarizes the latest information on HRT and cardiovascular disease, osteoporotic fractures, and cognitive function. The risks of HRT (e.g., stroke, breast cancer, and venous thromboembolism) clearly outweigh the benefits (e.g., reduction in osteoporotic fractures). The use of HRT for primary or secondary prevention of coronary heart disease or to decrease the risk of cognitive dysfunction is also not supported. While the evidence in older adults is substantial, there is some controversy regarding the effectiveness of HRT initiated in women at the start of menopause.
Key words: hormone replacement therapy, cardiovascular disease, osteoporosis, cognitive function, dementia.

Menopause: Current Controversies in Hormone Replacement Treatment

Menopause: Current Controversies in Hormone Replacement Treatment

Teaser: 

Marla Shapiro, CCFP, MHSc, FRCPC, FCFP, Assistant Professor, University of Toronto, Department of Family Medicine; Medical Consultant, CTV, Toronto, ON.

Whether women are taking hormone replacement therapy for the prevention of heart disease, osteoporosis or the symptoms of menopause, results from the Women's Health Initiative (WHI) study have brought to the forefront many concerns. Results from this as well as the HOPE study are reviewed, followed by the ensuing responses and recommendations from medical societies. Assessing and tailoring hormone replacement therapy for every woman individually is what can be recommended clearly until further studies are published.
Key words: menopause, hormone replacement therapy, current controversies

With a life expectancy of 81.

HRT: Illusions of a Magic Pill Shattered

HRT: Illusions of a Magic Pill Shattered

Teaser: 

Joanna Goldberg, MSc, Associate Editor, Geriatrics & Aging.

As a woman ages and approaches her menopause, one of the most important health decisions she will be faced with is whether to take hormone replacement therapy (HRT). The age-defying effects of HRT touted in the past by both the popular press and the medical establishment ranged from sustaining supple skin, youthful libido and a cheerful demeanor, to staving off osteoporosis, heart disease and dementia. Although contradicting evidence weighing these benefits against its associated risks have been trickling in for years, the recent results of a major NIH study will now dramatically change the way women and their general practitioners view HRT.

These results, released in May from the large U.S.-federally funded trial--part of a larger group of studies from the NIH-sponsored Women's Health Initiative--definitively showed for the first time that the risks associated with HRT exceed its benefits in healthy menopausal women. In fact, these conclusions were so striking that the trial involving over 16,000 women was stopped after a follow-up period of 5.2 years--three years short of its scheduled duration.

Back in the fall of 1997, approximately half of these participants, aged 50 to 79 years and all with an intact uterus, were randomized to receive either one daily tablet of the estrogen-progestin combination pill, Prempro (0.625mg conjugated equine estrogen and 2.5mg medroxyprogesterone acetate) or a placebo. The plan was to follow the women for an average of eight years and record how many heart attacks, strokes, blood clots, hip fractures and instances of colon cancer occurred. The first hint that all was not well came late in 1999, when the independent Data and Safety Monitoring Board unexpectedly observed a small but consistent increase in the risk of blood clots and heart attacks in the cohort of women taking HRT. Since then, the monitoring board has had similar inklings that HRT may render certain risks, and it was recommended that trial participants be informed of small increases in myocardial infarction, stroke and blood clots. However, the trial continued because the balance of risks and benefits remained uncertain.

The latest results, published in the July 19 issue of The Journal of the American Medical Association, differed from these previous observations in that the risk of invasive breast cancer crossed the pre-determined boundary established as a sign of risk. The alarm bells rang clear when the data were released: there were increases in the risk of breast cancer (26% higher among HRT-users), heart disease (29% higher) and stroke (41% higher), although the risks of colon and rectal cancer (37% lower) and hip fracture (33% lower) declined among women randomized to HRT.1

To all but those who for years remained skeptical, these results came as quite a surprise, and to millions of women taking HRT for various reasons, they were quite a nasty shock. But what exactly do the numbers mean for the individual woman who has been taking HRT for years or is considering it as she reaches menopause? Although the WHI trial results were reported in terms of relative risk, in order to apply them to clinical practice they must be translated into absolute risk. The absolute risk of harm to an individual woman is actually very small: among 10,000 women taking the studied combination of HRT for one year, there will be eight more invasive breast cancers compared to a group of 10,000 women taking placebo for one year (Table 1). There will also be seven more coronary heart disease events, eight more strokes and eight more pulmonary emboli among these women compared to their placebo-taking counterparts, but six fewer colorectal cancers and five fewer hip fractures. When the total number of events is considered, the excess number of events over the 5.2 years of the trial was one in 100 for women taking HRT, a finding that demonstrates how the risk adds up over time.

So what do these numbers mean for the primary care physician, to whom thousands of postmenopausal women will turn for answers? Long-term hormone therapy has, for years, been endorsed by the medical community to prevent disease and preserve health in postmenopausal women. The WHI study shows that HRT may, in fact, be doing the opposite, even though the absolute risk is low. Taking estrogen and progestin long-term in the hope of preventing a heart attack or stroke can no longer be considered a valid medical strategy. Primary care practitioners should, therefore, stop prescribing this estrogen-progestin combination for long-term use in healthy postmenopausal women for the prevention of chronic disease.

It may, however, still be reasonable for women to continue taking HRT for the short-term relief of menopausal symptoms. A very slight, short-term risk of blood clots seems to emerge as soon as women begin taking the hormones, yet the increased risk for stroke and breast cancer didn't appear until one and four years later, respectively. Every woman facing the choice of HRT for the short-term alleviation of menopausal symptoms must decide, with the support of her doctor, whether her symptoms are so intolerable that she is willing to take that very small chance of a complication. Alternative options for managing menopausal symptoms should be considered more seriously, including relaxation exercises for mood swings, low-dose estrogen creams or rings for vaginal dryness (see article, The Recognition and Management of Atrophic Vaginitis) and many natural remedies for hot flashes.

Although the WHI results cannot be extrapolated to other formulations of HRT, or even different doses of the same combination, other studies have reported increases in the risk of breast cancer as well. One such study found the incidence of all histologic types of breast cancer combined was increased from 60-85% in recent long-term users of HRT, whether the women were taking estrogen alone or in combination with progestin.2

The definitive proof coming out of the WHI trial has actually made menopause management a lot more complex. Although women are not advised to abruptly dump their HRT regimens, each should have a serious talk with her primary care physician to balance the absolute risks against the severity of her menopausal symptoms and the benefits she reaps from HRT. Perhaps it is also time to more actively explore alternative medications and well-proven therapies for heart disease, cancer and osteoporosis, and to focus on lifestyle modifications such as exercise, low-fat diet, and reducing blood pressure and cholesterol levels. The newer class of estrogen-like drugs called SERMS, such as raloxifene, is showing promise in reducing fractures without raising the odds of breast cancer.3 The results from the WHI study encourage us to return back to the basics, while looking ahead to the future with the hopes of alternative preventive strategies.

Source

  1. Writing Group for the Women's Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: Principal results from the Women's Health Initiative randomized controlled trial. JAMA 2002;288:321-33.
  2. Chen CL, Weiss NS, Newcomb P, et al. Hormone replacement therapy in relation to breast cancer. JAMA 2002;287:734-41.
  3. Khovidhunkit W, Shoback DM. Clinical effects of raloxifene hydrochloride in women. Ann Intern Med 1999;130:431-9.

Combining HRT and Alendronate better than HRT alone

Combining HRT and Alendronate better than HRT alone

Teaser: 

Fifty one papers relating to osteoporosis were presented at the American College of Rheumatology meeting in November 1998. One study by Lindsay and colleagues demonstrated that adding alendronate (Fosamax) to ongoing hormone replacement therapy (HRT) in women with postmenopausal osteoporosis provides significant increases in bone mineral density at the lumbar spin, hip and femoral neck. The study also found that adverse drug reactions were not significantly different in the Alendronate HRT combination group when compared to HRT and placebo. The combination was well tolerated. The study is targeted to be published by May 1999 in the Annals of Internal Medicine. To date there are no large published randomized clinical trials of the addition of bisphosphonates to HRT or vice versa.

All abstracts from the meeting are available at http://ex2.excerptamedica.com/98acr

HRT Controversy Unresolved Until 2005

HRT Controversy Unresolved Until 2005

Teaser: 

Anna Liachenko, BSc, MSc

A large body of observational evidence suggested that estrogen replacement therapy (ERT) after menopause decreases a women's lifetime risk of death from myocardial infarction by 35 to 50 percent and increases life expectancy by 2 to 3 years. However, a recent major clinical trial concluded that estrogen plus progestin therapy did not decrease the overall risk of myocardial infarction and coronary death among postmenopausal women with previous heart disease. The main question raised by the results of the trial is whether doctors should change their prescribing patterns and which patient populations will be affected. While there is no simple answer, it is important to consider the issues involved such as, How serious were the limitations of the observational research? Did the trial look at the right group of patients? How far can we extrapolate the results? And what are the future implications?

The Heart and Estrogen/progestin Replacement Study (HERS) trial was a randomized, blinded, placebo-controlled trial designed to test the efficacy and safety of hormone replacement therapy (HRT, estrogen plus progestin) on secondary prevention of heart disease. The trial involved 2763 postmenopausal women with established coronary artery disease. In the HRT group, the rate of coronary events increased by 50% in the first year of the trial and subsequently decreased by 40% in the forth and fifth years, yielding no significant effect overall.