Estrogen Analogs

Selective estrogen receptor modulators (SERMs) mimic estrogens in some tissues and anti-estrogens in others, and ideally provide the bone retaining effects of estrogen without its unwanted side effects. Currently, the only marketed SERM is raloxifene. This drug prevents bone loss and is indicated for the prevention and treatment of osteoporosis in postmenopausal women. In the Multiple Outcomes Raloxifene Evaluation (MORE) study, the incidence of new spinal fractures is reduced by 30-50% according to existence or not of vertebral fractures at baseline (1) – so far, no significant reduction in non-vertebral fractures has been reported outside post-hoc analyses performed in high risk subjects. Raloxifene has significant non-skeletal effects: in the MORE study, raloxifene significantly decreased the risk of invasive breast cancer in postmenopausal women, an effect that is sustained over 8 years (2). The NSABP Study of Tamoxifen And Raloxifene (STAR) study performed in postmenopausal women at high risk of breast cancer showed similar efficacy of raloxifene and tamoxifen, with a better tolerance of raloxifene (3).

Raloxifene is also known to lower serum cholesterol and does not induce endometrium bleeding or proliferation (4).The reduction of breast cancer was also confirmed in the Raloxifene Use for The Heart (RUTH) study, performed in women at high risk of cardio-vascular diseases. In that population, raloxifene had no effect on overall cardiovascular morbidity and mortality (5). In addition to minor side effects such as hot flushes leg cramps, peripheral edema, gallbladder disease, the RUTH trial showed that raloxifene use was associated with an increased risk of venous thromboembolic events (44%) and fatal stroke (49%) (5).

Other SERMs, such as bazedoxifene and lasofoxifene, are in the late stages of clinical development.

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