New Insights for Hormone Therapy in Perimenopausal Women Neuroprotection

Abstract

Perimenopause is a mandatory period in women's life, when the medical staff may initiate hormone therapy with sex steroids for the delay of brain aging and neurodegenerative diseases, during the so-called "window of opportunity." Animals' models are helpful to sustain the still controversial results of human clinical observational and/or randomized controlled studies. Estrogens, progesterone, and androgens, with their nuclear and membrane receptors, genes, and epigenetics, with their connections to cholinergic, GABAergic, serotoninergic, and glutamatergic systems are involved in women'sn o r m a lb r a i no ri n brain's pathology. The sex steroids are active through direct and/or indirect mechanisms to modulate and/or to protect brain plasticity, and vessels network, fuel metabolism-glucose, ketones, ATP, to reduce insulin resistance, and inflammation of the aging brain through blood-brain barrier disruption, microglial aberrant activation, and neural cell survival/loss.

Dissecting Sex-Related Cognition between Alzheimer’s Disease and Diabetes: From Molecular Mechanisms to Potential Therapeutic Strategies

“…The other hypothesis is the healthy cell bias of estrogen benefit. It assures that estrogen-only therapy shows its neuroprotective benefit when applied to the healthy neuron, and no beneficial effect was observed on neurons with mitochondrial damage [ 93 ].…”