Evista..... Wellness for Women?

On Dec. 10, 1997, the Food and Drug Administration (FDA) granted permission for Eli Lilly and Company to market raloxifene for the prevention of osteoporosis in postmenopausal women. Evista, Eli Lily's brand name for raloxifene, landed in U.S. pharmacies a month or two later.

The news about Evista had been, as MedicineNet's Chief Editor commented, "all over the press." So why deal with it here? Does the world need yet one more article about this drug?

Estrogen has been used for years for the prevention of both osteoporosis and coronary heart disease in postmenopausal women. Now, Evista is being highly heralded as an important alternative to estrogen replacement therapy.

The crowning of Evista, a custom-designed estrogen, as the next wonder drug is well underway. For example, the respected health writer Jane E. Brody did a piece about Evista entitled "Study Finds a New Estrogen Offers Benefit Without Risk" in The New York Times (Dec. 4).

Benefit without risk? That is the issue MedicineNet wishes to consider here for our viewers. Is it true or false? Is Evista a Fountain of Youth or, at least, a Fountain of Wellness for women?

First, a little background. As a woman enters menopause, her ovaries stop producing estrogen. Low levels of estrogen can cause a number of health problems. These include thinning and weakening of bones (osteoporosis), and increased blood levels of total and LDL cholesterol (the "bad cholesterol") with increased risks of atherosclerosis and heart attacks.

With life expectancy continuing to increase, women will soon spend fully one third of their lives after their menopause being deficient in estrogen. "The human and economic costs of this increased longevity in an estrogen- deficient state are substantial," as Dr. G. El-Hajj Fuleihan noted in an editorial in The New England Journal of Medicine (Dec. 4). These projected costs include an increase in cardiovascular problems, a leading cause of disease and death among postmenopausal women, and a marked rise in fractures due to osteoporosis that account for much morbidity and mortality after the menopause.

Osteoporosis affects millions of Americans. Some sources say "19 million" while others say "more than 28 million." In any case, a multitude of people in the U.S. (and many other countries) have osteoporosis, and the large majority of them are women. There are men with osteoporosis but far fewer. For that reason, we are going to focus here exclusively on women.

A woman can lose a quarter of her bone mass in the five years after her menopause. This loss weakens bones and sets the stage for painful fractures. These fractures can occur with minimal stress or trauma. According to the National Osteoporosis Foundation, the excess mortality rate during the year following a hip fracture is 20%. And a woman's risk of a hip fracture (a risk largely attributable to osteoporosis) is equal to her combined risk of breast, uterine, and ovarian cancer.

Estrogen replacement prevents osteoporosis in postmenopausal women by maintaining or rebuilding bone mass and thus lowers the chance of fractures related to osteoporosis. Long-term estrogen replacement also lowers the "bad" LDL cholesterol and raises the "good" HDL cholesterol, reducing atherosclerosis and decreasing the risks of heart attacks. And in addition, estrogen also alleviates hot flashes and other menopausal symptoms and may even help prevent Alzheimer's disease. All of these truly remarkable benefits of estrogen are reflected in the annual sales of $1 billion worth of Premarin (an estrogen therapy made by Wyeth-Ayerst) which is the #1 selling drug in the U.S.

Unfortunately, estrogen's benefits cannot be separated from its undesirable effects on the breasts and uterus. Estrogen replacement, as Dr. Pierre Delmas and his colleagues state in The New England Journal (Dec. 4), is "associated with an increased risk of endometrial cancer, which may persist despite the addition of a progestin, and perhaps also with an increased risk of breast cancer." In other words, replacement of the female hormone estrogen raises the risk of cancer of the uterus. Taking another female hormone, progesterone, in combination with the estrogen, lessens that risk but has not been found to eliminate it. Further, estrogen may increase the risk of breast cancer and progesterone does nothing to lower this risk.