Reclaiming menopause: another look at hormone replacement therapy and the medicalization of women's bodies.

A media frenzy erupted when the news broke in July 2002 that an U.S. government study of hormone replacement therapy (HRT) was halted midway because study participants were at a significantly increased risk for breast cancer, heart attack, stroke and blood clots. The Women's Health Initiative (WHI), funded by the National Heart, Lung and Blood Institute of the National Institutes of Health, did something rare in the scientific world: they stopped their clinical trial for HRT three years before the scheduled study conclusion because their preliminary findings demonstrated that the serious health risks associated with the long-term use of combined estrogen plus progestin greatly outweigh any health benefits.

But the study results were no surprise to the many women's health organizations who have been following the questionable methods used to promote the prescription of HRT to healthy midlife women. Short-term use of HRT has been documented in a variety of studies as a useful treatment for alleviating the temporary symptoms associated with the onset of menopause, such as hot flashes, night sweats and vaginal dryness. However, long-term use of HRT (more than five years), and the practice of prescribing HRT to healthy women--those not experiencing severe menopausal symptoms--is another matter. The WHI results are only the latest in a long series of studies demonstrating that long-term use of HRT should be considered only with extreme caution.

Yet for more than a decade, healthy women have been advised by medical practitioners and medical advisory bodies to take HRT when they reach menopause as a means to prevent heart disease and osteoporosis. Some of the more dubious pharmaceutical marketing and advertisements for HRT insinuate even more sensationalistic claims, leading women to believe that HRT reduces the signs of aging, cures depression and incontinence, prevents the onset of Alzheimer's disease, and much more. In other words, HRT has been touted as the miraculous "wonder drug" for midlife women. But somehow the science got lost along the way.

The last decade has seen an accumulated medicalization of menopause from a natural stage of a woman's life to an "ailment" or "disease" requiring a pharmaceutical "fix." Not incidentally, this occurred at precisely the moment when millions of baby-boom women across North America began entering midlife. The direct beneficiaries of the HRT-craze have been the pharmaceutical companies who have turned HRT into a multi-billion dollar industry. Wyeth, the makers of Premarin, the largest selling HRT formula in the US, sold US$2.07 billion in Premarin prescriptions last year alone, making it the company's best-selling drug.

But the losers of the HRT craze have been precisely those midlife women who were supposed to benefit from the health claims associated with HRT. The latest WHI study results are clear: the relative risks for long-term HRT (combined estrogen plus progestin for more than five years) constitutes a whopping 41% increased risk for strokes; 29% increased risk for heart attacks; a doubled risk for blood clots; a 22% increased risk for cardiovascular disease; and a 26% increased risk for breast cancer (cited from the WHI study site: www. nhlbi.nih.gov/new/press/02-07-09.htm).

Some media reports have downplayed the relative risks by citing the actual number of women at increased risk. At first glance, these numbers do appear meager; according to the WHI study, only eight more women in 10,000 will have breast cancer, seven more a heart attack, eight more a stroke, and 18 blood clots because of long-term HRT use. But when these numbers are evaluated with respect to the millions of women in North America currently on HRT, the result is in the range of tens of thousands of women at increased risk. No wonder women are sitting up and taking notice. The question that is on everyone's mind is: how could healthy women have been encouraged to take HRT for so long?

The confusion surrounding HRT comes from a combination of millions of dollars being spent on marketing hype and a poor evaluation of the scientific data. For many years observational studies were used to tout the benefits of HRT and were employed as part of the pharmaceutical push to market long-term HRT use for preventive measures (and not simply as a temporary relief for menopausal symptoms). But observational studies and clinical experience are known as "soft data" in the world of science--they are interesting, but too open to bias to constitute the necessary "proof" for the efficacy and safety of a medication required before it is put into widespread use. For this, only randomized, double-blind controlled clinical trials--the gold standard for health research--can produce credible results.

WHI constitutes the first mass-scale controlled trial to address the long-term risks and benefits associated with HRT use for healthy women. In other words, the practice of prescribing HRT to healthy women came before the medical evidence that should have underpinned HRT prescription guidelines. Other large clinical trials examining long-term HRT use have examined the practice of prescribing HRT to women with heart disease, such as the Heart and Estrogen/Progestin Replacement Study (HERS) and the Estrogen Replacement in Atherosclerosis (ERA) trial. These studies found that HRT does not reduce the risk of heart disease for midlife women but, as in the case of the HERS study, actually increases the risk for heart disease.

Over the years, these studies and a large number of other, smaller trials have shown long-term, constant HRT to be good for preserving bone mass but have also linked HRT to a long list of possible health risks, including breast cancer, gall bladder disease, cardiovascular disease, venous thromboembolism, biliary disease and more. Yet despite the troubling results from these shorter-term trials and the trials conducted on women with heart disease, HRT has continued to be routinely prescribed and recommended as a method of health preservation.

It would simply be too easy to lay the blame solely at the feet of the big pharmaceutical companies which, while performing an important function in our health services, are also in the business of turning a "healthy" profit. Rather, what needs to be addressed in this current HRT crisis is the logic of prescribing medications that have not yet been tested thoroughly in extensive clinical trials to otherwise healthy women.

Who will stand up and take the blame for letting "soft science" and marketing triumph over sound medical research? Where were our independent medical organizations and governing bodies to sound the alarm? There have been more than enough warnings that long-term HRT has serious health consequences for midlife women and that any benefits from HRT are more than outweighed by the risks. We can only hope for a revision of the medical and pharmaceutical guidelines that have perpetuated the promotion of HRT to healthy women in light of this new study. But one question remains: why has it taken so long?

At A Glance: The Women's Health Initiative Study

When did the study take place?

The study began in the fall of 1997 and was scheduled to be completed in 2005. However, researchers halted the study midway on May 31, 2002 after deciding that the health risks for participants taking HRT outweighed the possible benefits of HRT.

Who took part in the study?

More than 16,000 healthy postmenopausal American women with a uterus between the ages of 50 and 79.

What form of HRT was evaluated?

Participants were given either a placebo or 0.625 mg of conjugated equine estrogen and 2.5 mg of medroxyprogesterone acetate (HRT, estrogen plus progestin) in one tablet daily for an average of 5.2 years. The study was designed to evaluate the use of HRT by healthy women for disease prevention.

Why was the study halted?

The researchers halted the study prematurely because participants on HRT exceeded the boundary for breast cancer risk that was established at the beginning of the study. There was also an increased risk for heart disease for participants on HRT compared to the placebo group.

What are the relevant findings from this study?

The study suggests that long-term use of HRT (more than four years) increases a woman's risk for heart disease and breast cancer. The study demonstrated no significant increased risk of breast cancer for women taking HRT for less than four years.

Who needs to be concerned?

Researchers suggest that women who have been on combined HRT (estrogen plus a progestin) for more than four years should consult their doctors about whether they need to continue on HRT and address their increased risks for breast cancer and heart disease. Researchers also suggest that women taking HRT solely for heart disease prevention should stop taking HRT and consider other options.

While the study found that HRT does reduce the risk for fractures, researchers neverthless suggest that women taking HRT to prevent osteoporosis should weigh the risks of HRT against the possible benefits with their doctors and consider other, non-hormonal options for the treatment of osteoporosis.

What happens next?

The Women's Health Initiative study of unopposed estrogen (estrogen alone) therapy for women without a uterus will continue as planned since them is currently no sign of an increased risk of breast cancer for participants. Study results will be released after the trial ends in March 2005:

Sources: www.nhlbi.nih.gov/new/press/ 02-07-09.htm; JAMA 288(3), 321-333; A Friend Indeed May-June 2002; www. afriendindeed.ca; Canadian Women's Health Network: www.cwhn.ca

For more detailed information on the Pros and Cons of HRT, visit: www.cwhn.ca/resources/hrt/index.html

The author is the Director of Communications for the Canadian Women's Health Network. For more information about CWHN, visit their website: www.cwhn.ca. Kathleen is also the Editor of A Friend Indeed newsletter for women in menopause and midlife where this article first appeared (July-August 2002). To subscribe or view other articles, go to: www.afriendindeed.ca or contact Kathleen O'Grady, e-mail: [e-mail]