Review of the effects of 17alpha-estradiol in humans: a less feminizing estrogen with neuroprotective potential Export

@article{citeulike:4099204, abstract = {17alpha-Estradiol is a less feminizing isomer of the potent hormonal estrogen, 17beta-estradiol. 17alpha-Estradiol is an orally active small molecule with conflicting reports of efficacy in preclinical models of degenerative diseases. A number of studies suggest neuroprotective potential in human neurodegenerative disorders, including Alzheimer's disease (AD) and Parkinson's disease. Several studies have established an antioxidant effect of 17alpha-estradiol in humans. The sodium salt of 17alpha-estradiol 3-sulfate is a minor component (2.5-9.5\%) of several widely marketed estrogen hormone replacement products, such as Premarin®, that are approved by the U.S. Food and Drug Administration and have been prescribed and studied in women and men for more than 65 years. Most of the more than 100 published reports on the neurological effects of feminizing estrogens found positive responses in at least one measure relating to cognition or prevention and treatment of AD, notwithstanding the negative results in the Women's Health Initiative studies. Whether these limited, and often not statistically significant, findings are clinically meaningful remains unknown. In many in vitro and in vivo preclinical neuroprotection and related studies, 17alpha-estradiol and 17beta-estradiol are active at similar concentrations and doses. However, 17alpha-estradiol is less pleiotropic than 17beta-estradiol, and thus its potential toxicity might be lower. Given decades of mixed reports regarding the potential efficacy and safety of strongly feminizing hormones in neurodegenerative diseases, the weakly feminizing 17alpha-estradiol might be a suitable candidate for clinical testing of the neuroprotective potential of this chemical class because it avoids, or significantly reduces, the adverse effects of potent hormonal compounds. Drug Dev Res 70:1-21, 2009. {\copyright} 2009 Wiley-Liss, Inc.}, address = {MIGENIX, San Diego, CA; MIGENIX, Vancouver, BC, Canada}, author = {Moos, Walter H. and Dykens, James A. and Nohynek, Dana and Rubinchik, Evelina and Howell, Neil}, citeulike-article-id = {4099204}, citeulike-linkout-0 = {http://dx.doi.org/10.1002/ddr.20284}, citeulike-linkout-1 = {http://www3.interscience.wiley.com/cgi-bin/abstract/122186505/ABSTRACT}, doi = {10.1002/ddr.20284}, journal = {Drug Development Research}, keywords = {17, 17alpha, alpha, estradiol}, number = {1}, pages = {1--21}, posted-at = {2009-02-25 14:55:01}, priority = {2}, title = {Review of the effects of 17alpha-estradiol in humans: a less feminizing estrogen with neuroprotective potential}, url = {http://dx.doi.org/10.1002/ddr.20284}, volume = {70}, year = {2009} }

TY - JOUR ID - citeulike:4099204 L3 - citeulike-article-id:4099204 N2 - 17alpha-Estradiol is a less feminizing isomer of the potent hormonal estrogen, 17beta-estradiol. 17alpha-Estradiol is an orally active small molecule with conflicting reports of efficacy in preclinical models of degenerative diseases. A number of studies suggest neuroprotective potential in human neurodegenerative disorders, including Alzheimer's disease (AD) and Parkinson's disease. Several studies have established an antioxidant effect of 17alpha-estradiol in humans. The sodium salt of 17alpha-estradiol 3-sulfate is a minor component (2.5-9.5%) of several widely marketed estrogen hormone replacement products, such as Premarin®, that are approved by the U.S. Food and Drug Administration and have been prescribed and studied in women and men for more than 65 years. Most of the more than 100 published reports on the neurological effects of feminizing estrogens found positive responses in at least one measure relating to cognition or prevention and treatment of AD, notwithstanding the negative results in the Women's Health Initiative studies. Whether these limited, and often not statistically significant, findings are clinically meaningful remains unknown. In many in vitro and in vivo preclinical neuroprotection and related studies, 17alpha-estradiol and 17beta-estradiol are active at similar concentrations and doses. However, 17alpha-estradiol is less pleiotropic than 17beta-estradiol, and thus its potential toxicity might be lower. Given decades of mixed reports regarding the potential efficacy and safety of strongly feminizing hormones in neurodegenerative diseases, the weakly feminizing 17alpha-estradiol might be a suitable candidate for clinical testing of the neuroprotective potential of this chemical class because it avoids, or significantly reduces, the adverse effects of potent hormonal compounds. Drug Dev Res 70:1-21, 2009. © 2009 Wiley-Liss, Inc. IS - 1 JF - Drug Development Research AD - MIGENIX, San Diego, CA; MIGENIX, Vancouver, BC, Canada EP - 21 TI - Review of the effects of 17alpha-estradiol in humans: a less feminizing estrogen with neuroprotective potential VL - 70 SP - 1 KW - 17 KW - 17alpha KW - alpha KW - estradiol AU - Moos, Walter AU - Dykens, James AU - Nohynek, Dana AU - Rubinchik, Evelina AU - Howell, Neil PY - 2009/// UR - http://dx.doi.org/10.1002/ddr.20284 ER -