A novel strategy to improve women’s health: selective estrogen receptor modulators

Tamoxifen is the first selective estrogen receptor modulator. The extensive clinical and laboratory testing during the 1980s and 1990s raised questions about why there is target site specificity of tamoxifen in different species, i.e., tamoxifen is an estrogen in mice but a complete anti-estrogen in chicks. Additionally, tamoxifen has estrogen-like effects to lower circulating cholesterol, build postmenopausal bone in women, and stimulate the uterus and endometrial cancer growth but paradoxically prevents breast tumor growth. These observations lead to the SERM solution to prevent osteoporosis with a safe SERM but to prevent breast cancer at the same time. Raloxifene is the result with no increase in endometrial cancer incidence. There are now five FDA-approved SERMS available for use: tamoxifen, raloxifene, bazedoxifene, toremifene, and ospemifene. All have connections with discovery and basic research in Jordan’s laboratory.