Raloxifene.

Abstract

Raloxifene is a selective estrogen receptor modulator, a compound that has estrogen agonist activity at some sites and antagonist activity at others. In investigations in animals and in rigorously conducted trials in humans, raloxifene treatment is associated with a 30%-40% reduction in risk of one or more spine fractures using the 60 mg dose. This reduction in risk is found in women with or without baseline fractures, in women with bone mineral density (BMD) in the lower, middle, or upper third of the low range (all had BMD reduced by more than 2.5 SD) and in women aged less than 65 years, between 65-70 years, and greater than 70 years. A reduction in ankle fractures, but not hip or wrist fractures, was found. Raloxifene treatment also is associated with a 60%-70% reduction in risk for breast cancer and is associated with reduced total and LDL cholesterol, lower fibrinogen, and no rise in triglyceride. Reduced aortic wall cholesterol content is reported in animal studies. These are surrogate endpoints of cardioprotection. There is no evidence that raloxifene reduces the incidence of myocardial or cerebrovascular events. Raloxifene does not induce breast tenderness, endometrial hyperplasia, menstrual bleeding, or endometrial cancer, but may be associated with an increased risk of thromboembolic disease (1/1000 cases per year), leg cramps in 2%-4% of cases and hot flushes in 4%-6% of cases, usually in first 6 months.