This week's headlines announcing the abrupt termination of part of the Women's Health Initiative -- the definitive long-term study of 16,000 postmenopausal women to investigate the benefits and risks of hormone replacement therapy (HRT) -- caught many medical practitioners and their patients by surprise. The portion of the study involving women taking a combination of estrogen and progesterone was halted suddenly due to substantially increased risks for an aggressive form of breast cancer, as well as notably increased odds for heart attack, stroke and blood clots in women participating in HRT as "treatment" for menopause.
For researchers who have long maintained a healthy skepticism about hormone replacement therapy, the sudden halt of part of the study was not a surprise, but rather a relief after a recent string of bad news about the medicinal use of hormones. It started last July when the Annals of Internal Medicine reported the results of two studies contradicting the long-held belief that hormone replacement therapy protected postmenopausal women's hearts. One review concluded that for women with heart disease, hormones actually increased the risk of heart attacks and death by 25 percent. A second study echoed those results, finding that women who started HRT after having a heart attack were 44 percent more likely to have another heart attack or die within a year when compared to those who never used hormones. (The one major study that ever showed estrogen could reduce heart attacks had been based on men.)
In February, the Journal of the American Medical Association (JAMA) printed the results of an extensive study showing that women who took hormone therapy for five years or more after menopause had a 60 to 85 percent increased risk of breast cancer, especially a type known as lobular tumors, which account for up to 10 percent of all breast cancers. The findings applied equally to women taking estrogen alone, or in combination with another hormone, progesterone, which had long been touted by HRT proponents as the safety additive to the hormone cocktail.
In that same issue, JAMA reported that HRT, long touted for improving the mental outlook for postmenopausal women, does not often help, and may in fact physically harm them. The study covered more than 2,700 women, whose average age was 67. The results, concluded Dr. Kathryn M. Rexrode, a Harvard Medical School instructor and coauthor of the study, "should challenge the widely held belief that hormone therapy helps women remain more youthful, active or vibrant." Rexrode went on to say that "the overall data over the last few years suggest that fewer women than we thought are benefiting from hormone replacement therapy," and concluded that "there is very much we don't know about HRT."
The bad news for HRT proponents continued into April. Conventional wisdom had long held that hormone therapy protected women against ovarian cancer. However, a Swedish study refuted that by showing some forms of hormone replacement might actually increase a woman's risk of this deadly disease. The Journal of the National Cancer Institute reported that two forms of hormone replacement therapy -- estrogen alone and estrogen with limited use of progestins, the synthetic form of progesterone -- may increase the risk of epithelial ovarian cancer, a form of the disease involving cells covering the outer surface of the ovaries. In women who still had their uterus and used estrogen alone for 10 years, there was a 43 percent increased risk of ovarian cancer compared to women who never used estrogen therapy.
The Swedish researchers also found that women who had used estrogen combined with sequential progestin were up to 54 percent more likely to develop epithelial ovarian cancer than those women who never used this therapy. This study reinforced one published in 2001 in JAMA that found that women who used estrogen therapy for more than 10 years had double the risk of ovarian cancer.
In May, British researchers who had followed 13,000 women for three years reported that those who took HRT were three to four times more likely to develop debilitating gallstones. This confirmed similar findings in the Nurses' Health Study, a large study underway in the United States.
These are devastating findings for my generation -- baby boomers -- who have been repeatedly assured that hormone replacement therapy not only offers freedom from the uncomfortable physical symptoms of menopause, but also improves heart health and bone strength, all with virtually no extra cancer risk. It turns out to be a lie -- a 50-year-old lie.
Major pharmaceutical companies have been using women -- duping women -- since the 1950s when a few doctors started classifying menopause as "estrogen deficiency disease," as if this natural passage was an affliction that needed medication for treatment. Doctors "treated" us with tranquilizers and antidepressants. By the 1960s, with an onslaught of advertising money from Wyeth, the manufacturer of the top-selling estrogen product, hormones became the "cure" of choice for menopause.
It wasn't until the 1970s that doctors discovered a problem: Estrogen greatly increased the risks of uterine cancer. Hardly discouraged, the pharmaceutical companies went back to the lab and developed a mixture of estrogen and progesterone designed to block the uterine cancer risk. A relentless bid to expand the market accompanied the new menopause "cure." After initially claiming that hormones only assisted with the symptoms of menopause such as hot flashes, the drug companies steadily added to the list of things it was supposed to help, from bone density, to heart health, to sexual vigor, to enhanced memory, to curing depression.
Every time a study has been released that has challenged the safety of hormone replacement therapy, the pharmaceutical companies have gone into high gear to minimize the results and find new reasons for women to continue swallowing the drugs. They have scared women into thinking they will fall apart when they reach menopause -- even worse, cease to be attractive -- if they don't start taking hormones. If history is any guide, researchers at Wyeth are trying even now to package a new combination of hormones to replace the tainted brew.
The payback for the last 30 years of false advertising is this week's news that millions of women have put themselves at increased risk for life-threatening illnesses because pharmaceutical companies and obliging doctors have marketed eternal youth in a dangerous hormonal cocktail disguised as a wonder drug.
Will women, embarrassed by aging and the intimacy of this discussion, continue to be silent? Are we resigned to playing the role of guinea pig for large pharmaceutical companies scrambling to develop profitable treatments? The answer is yes to both questions if we continue to approach menopause as the end of our reproductive ability and sexual attractiveness. We have become convinced that, instead of a new start, menopause signals the end of a vibrant phase of life -- and drug companies have long profited from our insecurities about this natural change. They have capitalized on women's fear, and in the process put millions of us at greater risk of serious disease. Now it is our turn to capitalize on the duplicity of drug companies to put them at risk of serious regulation.