Toremifene

After decades of selling American women and doctors on the idea that menopause is an illness that must be treated with lifelong estrogen therapy, the pharmaceutical industry is poised to unleash yet another class of hormone drugs that, not surprisingly, should be taken indefinitely. For over a year, these so-called designer estrogens have been touted at professional conferences as the answer to a middle-aged womans prayers because they have the heart- and bone-protective benefits of estrogen without the risks of uterine and breast cancers. These selective effects are the reasons why the new drugs are called selective estrogen-receptor modulators (SERM). A new study verified two modest benefits of raloxifene (brand name: Evista), the first designer estrogen to be approved by the FDA. It will become available this month; other versions, including toremifene and clomiphene, are on their way. They are expected to make a major dent in the $1 billion-a-year sales of Wyeth Ayersts Premarin, the top-selling brand of estrogen.

The new study, financed by raloxifenes manufacturer Eli Lilly, randomly assigned 601 healthy, white postmenopausal women to receive either a placebo, or a 30-, 60-, or 150-mg dose of raloxifene for two years (New England Journal of Medicine, 4 December 1997). All participants had the bone density of the lumbar spine, hip, and total body measured before and after the study, as well as blood levels of cholesterol. The investigators, Pierre D. Delmas, M.D., Ph.D., from the Hpital Edouard Herriot in Lyons, France, and colleagues, found that the women given raloxifene did better at any dose than the women given placebos. But the investigators measured bone density, not fracture, and improvements in blood lipids, not reductions in the rate of heart attack and stroke.

The higher the dose of raloxifene, the greater the increase in bone density. For example, the women taking 150-mg doses daily showed a slightly more than 1% increase in bone density in the lumbar spine and the hip, whereas, the placebo group lost about that amount. Investigators call this a significant improvement, but to the individual women deciding whether to take raloxifene, the benefit is modest. Similarly, ralox-ifene lowered total chole-sterol levels by 6.4%. The drug did nothing to increase levels of good cholesterol called high-density lipoprotein, but it did reduce by 10% the bad cholesterol levels.

The main reason women currently take estrogen is to alleviate the hot flashes associated with menopause, yet raloxifene did nothing to reduce this symptom. Moreover, the rate of vaginal bleeding was identical in the placebo and the raloxifene groups. As for raloxifenes purported lack of cancer-causing effects, a two-year follow-up does not provide definitive answers, but researchers point to promising signs. For example, the drug does not have estrogens stimulatory effects on the endometrium, or lining of the uterus. (An increase in endometrial cancer was one of the early adverse effects noted for estrogen therapy.) So too, animal studies indicate that raloxifene has little estrogenic action on breast or uterine tissue. Raloxifene appears to be less potent than estrogen at preserving the bones and improving cholesterol levels, but the woman who must decide between the two drugs will have little to guide her. The only trial to compare estrogen, raloxifene, and a placebo lasted only eight weeks,suggesting that estrogen is superior to raloxifene in increasing levels of good cholesterol.

In an editorial that accompanied the new raloxifene study, Ghada El-Hajj Fuleihan, M.D., rightly observes that raloxifenes ability to prevent fractures and cardiovascular events is yet to be determined. But he espouses a common misperception on the part of gynecologists that the current generation of middle-age women is the first to live one-third of their lives beyond menopause. In fact, many gynecologists have publicly expressed the belief that this is the first generation to live beyond menopause. This is not only absurd but also dangerous, for it conveys the idea that women, once they cross the threshold of age 50, are entering uncharted territory fraught with hip fracture and heart attacks.

Countering this standard medical point-of-view is Dutch gynecologist Eylard V. Van Hall, M.D., who observes, Over the past 150 years, the average life expectancy of women has doubled from 40 to 80 years. These data relate to life expectancy at birth; interestingly enough, life expectancy at the age of 65 has only increased four years for women and has remained unchanged for men over the same period. The only new development, Dr. Van Hall explains, is that the total proportion of women reaching old age has substantially increased (International Journal of Risk & Safety in Medicine 10, 1997, 71-74).

Gynecologists have long regarded menopause as a hormone deficiency disease and have thus provided a willing audience for a pharmaceutical industry intent on portraying menopause as an illness requiring drug treatment. Wyeth Ayersts TV ad is one of the more outrageous examples. Though its estrogen drug goes unmentioned in the ad, Wyeth Ayerst is clearly selling the message that menopause is an illness. Menopause is more than hot flashes is the theme of the ad, which falsely claims that after menopause a womans risk of heart disease nearly equals that of a mans. In fact, women are consistently about ten years older than men at the initial manifestation of heart disease and about 20 years older at first heart attack (Coronary Heart Disease in Women, Cardiovascular Review & Reports, December 1993).

Interestingly, longevity, the universally accepted measure of good health, appears to have little relevance to medical care. Women outlive men in virtually all countries, whether the per person expenditure on medical care is $4,000 (U.S.), $704 (Greece), or $1,581 (Japan, where women have the highest rate of longevity). This important point is invariably lost in the medical discussion of older womens health.

COPYRIGHT 1998 Center for Medical Consumers, Inc.
COPYRIGHT 2000 Gale Group