Estrogens, progestins, menopause and neurodegeneration: basic and clinical studies

Area of Science:

• Neuroscience
• Endocrinology
• Pharmacology

Background:

• Ovarian steroids, including estrogens and progestins, exhibit neuroprotective properties.
• Neuronal vulnerability increases with the decline of these steroids, particularly after menopause.

Purpose of the Study:

• To review evidence supporting the neuroprotective roles of estrogens and progestins.
• To explore potential mechanisms underlying their neuroprotective effects.
• To highlight the need for clinical trials investigating these steroids for neurological conditions.

Main Methods:

• Review of in vitro and in vivo studies on estrogens and progestins.
• Examination of models for cerebral ischemia, brain trauma, and Alzheimer's disease.
• Analysis of signaling pathways involved in steroid-mediated neuroprotection.

Main Results:

• Estrogens demonstrate neuroprotection across various models, including those relevant to Alzheimer's disease, with a mitochondrial mechanism implicated.
• Progestins activate similar neuroprotective pathways as estrogens and show efficacy in models of acute neuronal injury.
• Animal and cell culture data suggest menopause-related steroid loss compromises brain resilience.

Conclusions:

• Estrogens and progestins offer significant neuroprotection against acute and chronic neuronal damage.
• The decline of ovarian steroids may increase susceptibility to neurodegenerative diseases.
• Further clinical studies are warranted to evaluate therapeutic regimens of estrogens and progestins for brain health.