Osteoporosis - EVISTA..... Wellness for Women?

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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 in

crease, 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 ca

nnot 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.

Evista belongs to a class of new drugs called selective estrogen receptor modulators (SERMs). SERMs work by slipping like a key in a lock into the estrogen receptors in some tissues (like bone) but not others (like the uterus). Thus, a SERM can act like estrogen on certain tissues (such as bone), but not on other tissues (such as the uterus).

The first SERM to reach the market was tamoxifen which blocks the effect of estrogen to stimulate breast tissue. Tamoxifen has proven valuable in women who have had cancer in one breast in preventing cancer in the second breast. (Tamoxifen is sold under the trade name Nolvadex by Zeneca Pharmaceuticals).

Evista is the second SERM to be approved by the FDA. In animal studies and a number of studies involving postmenopausal women, Evista was found to increase bone mass and prevent osteoporosis and lower total and LDL cholesterol. A study that may have hastened the FDA's approval of Evista was reported in The New England Journal (Dec. 4) by a team headed by Pierre Delmas. It involved some 600 postmenopausal women in a 2- year trial of Evista. The trial confirmed that "Daily therapy with raloxifene increases bone mineral density, lowers serum concentrations of total and low-density lipoprotein (LDL) cholesterol, and does not stimulate the endometrium."

However, Evista has a number of negat

ive features including some side effects. These go beyond hot flashes -- Evista does nothing for hot flashes - and mild leg cramps. A serious side effect of Evista is the increased risk of venous thrombembolic events (VTEs), the development in veins of blood clots (thrombophlebitis) that can break off and travel to the lungs, a process called pulmonary embolism. There is a 2 1/2 times increase in the risk for VTEs in women treated with Evista. Although estrogen therapy carries a comparable VTE risk, it is a disappointment that Evista does nothing to diminish that risk.

It is also disappionting that there is as yet no proof that Evista prevents heart disease. It may or it may not. Evista fails to change the blood levels of the "good" HDL cholesterol or the triglycerides, which is worrisome. And Dr. William Andrews, past president of the American College of Obstetrics and Gynecology (ACOG) told the Associated Press (Dec.10) that a monkey study about to be published shows Evista lacks the beneficial effects of estrogen upon the heart.

The real large-scale experience with Evista is about to begin. With any new medication, careful long-term studies and followups are necessary to establish the drug's long-term safety and effectiveness. Certain side effects may not be recognized until months or years have passed after the drug is released.

Based on the available information, medical scientists (MedicineNet editors included) believe that Evista will be a useful option for postmenopausal women. New options are sorely needed. At present, only 20% of postmenopausal woman who are considered candidates for estrogen replacement take estrogen. Whether the availability of both estrogen and Evista will raise this proportion remains to be seen.

Viewers are reminded that estrogen an

d Evista may be important but they are not the only measures women can take to prevent postmenopausal osteoporosis. Other very important measures to take are calcium supplements and life-style changes including regular exercise, stopping cigarette smoking and curtailing alcohol consumption. Lack of exercise, cigarette smoking and excessive alcohol consumption aggravate osteoporosis. However useful is proves to be, Evista alone is not the Fountain of Wellness for women.

For more information please visit the MedicineNet.com Osteoporosis Center in the Diseases and Conditions area.

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Reviewed on 8/13/2002

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