In search of neuroprotective therapies based on the mechanisms of estrogens

Although estradiol is a neuroprotective factor, estrogen therapy in older women increases the risk of adverse cognitive outcomes and poses additional peripheral risks, requiring careful use of estrogenic compounds as treatments for neurodegenerative conditions or neural injury. Potential alternatives to estrogen therapy to promote neuroprotection might include treatment with molecules that are able to interact with estrogen receptors, with alternative mechanisms of action, or with molecules that induce local estradiol synthesis in the brain, or a combination of all. However, before considering the broad clinical applications, more basic research is required to clarify the mechanisms of action and potential risks of some of these estrogen-based treatments.