Selective estrogen receptor modulators (SERMs) are medications that act like estrogen in certain tissues (eg, bones) and block the influence of estrogen in others (eg, breast tissue). One SERM, raloxifene, is currently used to prevent and treat osteoporosis , and has shown promise in preventing breast cancer in postmenopausal women. Some studies have indicated that raloxifene may be associated with improvements in cholesterol and other markers of cardiovascular risk, but it is not clear how raloxifene actually affects the risk of coronary heart disease (CHD).

A new study in the July 13, 2006 New England Journal of Medicine investigates the effects of raloxifene in women with CHD and those at increased risk. The researchers found that while raloxifene reduced the risks of breast cancer and spine fractures, it increased the risks of fatal stroke and blood clots.

About the Study

This study, called the Raloxifene Use for The Heart (RUTH) trial, included 10,101 postmenopausal women in 26 countries who had CHD or were at high risk for CHD (eg, women over the age of 70 with high blood pressure and high cholesterol). The women were randomly assigned to receive 60 milligrams of raloxifene or a placebo (dummy) pill daily. The researchers followed the women for an average of 5.6 years, during which time the women underwent regular electrocardiograms , mammograms , cholesterol checks, and other assessments for CHD and other medical problems.

There was no difference between the raloxifene and placebo groups in the risk of having a coronary event (defined as dying from heart disease, having a heart attack , or being hospitalized with a heart problem). The women taking raloxifene experienced decreases in low-density lipoprotein (LDL, or “bad”) cholesterol and increases in high-density lipoprotein (HDL, or “good”) cholesterol. Raloxifene was associated with a 35% reduction in the risk of spine fractures and a 44% reduction in the risk of invasive breast cancer (primarily due to a decreased risk of estrogen-receptor-positive breast cancers).

However, compared with the placebo, raloxifene increased the risk of blood clots by 44% and fatal stroke by 49%. The women taking raloxifene were more likely to experience hot flashes, leg cramps, swelling of the legs and feet, and gallbladder disease.

This study was funded by Eli Lilly, which is the pharmaceutical company that manufactures raloxifene.

How Does This Affect You?

These findings suggest that even though raloxifene was associated with improvements in cholesterol levels of women with or at risk for CHD, it did not reduce their risk of having coronary events over a 5 or 6 year period. Reduced risks of invasive breast cancer and spine fractures were identified as benefits of raloxifene, and increased risks of blood clots and fatal stroke were identified as drawbacks.

Based on these results, who should take raloxifene? This study does not provide a clear answer, but it appears that it will most likely benefit women at high risk for spine fractures or invasive breast cancer, and low risk for blood clots and stroke. When deciding whether you should take raloxifene, you and your doctor should carefully review your individual disease risks and the unpleasant side effects you may experience if you take the medication. Your doctor will only prescribe raloxifene if the benefits outweigh the risks in your particular situation.