Selective estrogen receptor modulators (SERM) for the brain: Recent advances and remaining challenges for developing a NeuroSERM™

Estrogen regulation of cognitive function and prevention of neurodegenerative disease has come to be of major scientific and clinical importance. While these functions rank paramount among concerns of women during menopause, the neoplastic risks associated with estrogen and hormone replacement therapy lead most women to elect against hormone intervention during menopause or to seek alternative estrogens in an attempt to ameliorate menopause‐associated deficits and disease risks. Development of an effective selective estrogen receptor modulator (SERM) for use as an alternative to hormone replacement therapy must address the issues of efficacy in and availability to the brain. Abrief review of estrogen effects on cognition, neuroprotective capability, and disease prevention is provided followed by an analysis of current knowledge regarding SERM efficacy in brain. Lastly, the challenges that remain for developing an effective NeuroSERM™ are considered. Drug Dev. Res. 56:380–392, 2002.