TWO NEW BOOKS THAT TAKE A CRITICAL LOOK AT HORMONE THERAPY
By Maryann Napoli
(July 2003)

The bad news about postmenopausal hormones came in increments. In July 2002, the Women's Health Initiative trial was stopped prematurely because the estrogen/progestin combination drug called Prempro was-over a five-year period-causing more diseases than it was preventing. Then eight months later, the WHI produced another unexpected finding: hormone drugs aren't all that helpful to women taking them to alleviate hot flashes.

In time, widely advertised hopes that estrogen could prevent Alzheimer's disease were dashed when the WHI showed that the women taking Prempro had a higher rate of this much-feared disorder. And if that weren't bad enough, last month a study involving one million British women found a substantially higher rate of breast cancer deaths among those had taken combination hormones than those who did not or those who took estrogen alone (The Lancet, 8/9/03).

So many questions remain. Why were gynecologists unanimously convinced that long-term hormone "replacement" therapy would prevent heart disease? Why were the adverse effects shown only for combination hormones and not estrogen alone? Are there any safe and effective alternatives for women who were taking hormones to alleviate menopausal symptoms? Two new books provide some answers.

For Susan M. Love, MD, the much admired breast surgeon, the underlying question that the WHI raises for her is why women need to replace hormones in the long term. Women require high levels of hormones to reproduce, she says, then they shift down to lower levels for the second half of life. In her latest book, Dr. Susan Love's Menopause & Hormone Book, written with Karen Lindsey (New York: Three Rivers Press, 2003), Dr. Love notes that the marketing of hormone "replacement" therapy went hand in hand with the idea that once menopause begins, a heart attack or hip fracture will soon follow. Diseases of aging, like heart disease and osteoporosis, were reclassified as diseases caused by menopause. Both were portrayed as estrogen-deficiency diseases.

In The Greatest Experiment Every Performed on Women: Exploding the Estrogen Myth (NewYork: Hyperion, 2003), journalist Barbara Seaman writes that many women injured by hormones were bullied by their doctors into taking estrogen that they didn't want or need; now many of them are being bullied by lawyers who also may not know what they are doing. In her 1969 ground-breaking book The Doctors' Case Against the Pill, Seaman almost single-handedly started the women's health movement when she brought public attention to the serious, sometimes fatal, health risks associated with oral contraceptives because the products sold in the 1960s had more than ten times the amount of hormones needed to prevent pregnancy.

The Greatest Experiment starts 65 years ago when a British biochemist published his formula for a cheap and powerful oral estrogen. Within months, writes Seaman, thousands of doctors and scores of drug companies around the world were working with this formula, prescribing it to slow and prevent aging, to stop hot flashes, to avoid pregnancy or miscarriage, and as a morning-after contraceptive. The risks of these drugs were known and documented from the start, according to Seaman, whose research shows that the British doctor who published his estrogen formula in 1938 spent many years warning that, though these drugs had great promise, they also put women at serious peril. He would become the first of several doctors to warn about giving hormones to healthy women.

Seaman, whose aunt died of estrogen drug-induced endometrial cancer, takes us through the subsequent decades of early failed attempts to study estrogen's safety and efficacy as a contraceptive; the widespread prescription of the synthetic estrogen called DES to prevent miscarriage (it couldn't, but that didn't stop its use); the marketing of estrogen as an anti-aging panacea; and then brings the reader right up to recent years when healthy women were told to take estrogen to prevent heart disease and hip fractures. The injuries and deaths that occurred along the way did not seem to deter doctors and drug companies, nor did the lack of evidence to support the broad range of health claims. (Research has proven estrogen to be safe and effective only for alleviating symptoms of natural and surgical menopause.)

Seaman provides a behind-the-scenes view of the effectiveness of the women's health activists who can be credited for-among many other things-getting written information about side effects, warnings, etc. mandated for all hormone drugs. When Wyeth-Ayerst asked the FDA to approve its estrogen drug Premarin for the prevention of heart disease, no professional medical society objected to the request. It was Cindy Pearson of the National Women's Health Network who was the most vigorous dissenter. She successfully pressured the FDA to have the written information include the fact that estrogen has never been proven to prevent heart disease.

At a 1996 FDA meeting about the perennial fight to have written information with all prescription drugs, Seaman managed to get the then head of the AMA to admit publicly why his organization has been so adamantly against the idea. Dr. Roy Schwartz conceded Seaman's points-that the provision of written information for hormone drugs had saved lives and reduced malpractice suits. Almost half of all prescriptions are written for conditions that are unproven, he explained. Doctors don't want their patients to know they are getting a drug for [what is called] an off-label use, continued Dr. Schwartz, adding that people might sue their doctors for an injury incurred by a drug prescribed off-label.

While Seaman's book provides the historical perspective that should make any reader into an educated skeptic once the next "miracle" drug comes along, Love's book takes on the question of what menopausal women can do now that the all-purpose menopausal drug has been knocked from its pedestal. There are lots of options for women who want to prevent diseases of aging without resorting to estrogen, she writes, offering five chapters on non-drug approaches to symptom relief, as well as lifestyle changes. Some women suffer so severely from night sweats and hot flashes that they are willing to risk taking the drug for a year or so. Love provides easy-to-understand ways of weighing risks, not only of taking the combination hormones but also of developing the diseases of aging. In the WHI, taking estrogen alone, a choice available only to women without a uterus, appears to be safe-for now. This is the only group of participants allowed to continue to the trial's originally intended end in 2006. As new research becomes available, Love advises women to be prepared to reevaluate their decisions.

One way for drug companies to sell mid-life women on the idea of lifelong hormone therapy was to sell fear of a potentially fatal hip fracture. Never mind that the odds of this occurring before age 70 are pretty slim. (Ironically, the WHI provided the first scientific evidence that combination hormones actually can reduce the rate of hip fracture.) Osteoporosis moved into the female collective consciousness in the 1980s. The chief culprit was purportedly loss of estrogen. What was once a risk factor (bone loss) has been turned into a disease, writes Love. Not so long ago, a woman did not have osteoporosis unless she had a fracture. A panel of international experts redefined osteoporosis as "a disease characterized by low bone mass and microarchitectural deterioration of bone tissue, which lead to increased bone fragility and a consequent increase in fracture risk."

This greatly expands the number of people who now have a disease, writes Love, who observed that doctors and drug companies have focused women solely on the first half of that definition-low bone density. However, some researchers have found that bone architecture, or bone strength, is a far better determinant of who will suffer a hip fracture. No test can accurately measure bone strength so doctors test what they can-bone density-and continue to rely on dual-energy X-ray absorptiometry (DEXA). This test, suggested for all women over age 60 in osteoporosis ads by Merck, the maker of an osteoporosis drug, has caused many women to be diagnosed with what Love thinks is a made up condition. Osteopenia (reduced bone mass) is not a disease and not even a risk factor, she writes, and should not be treated. However, a DEXA-produced diagnosis of osteopenia led many a woman to an estrogen prescription.

Both books are written by women who have been at the vortex of the estrogen controversy for many years. Both authors are high-profile activists long known to have women's best interests at heart.