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.

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Endocrine and neural senescence overlap in time, by intertwined complex feedback loops. Womens' brain is genetically more prone to suffer during life, and perimenopause is a "critical period" in neuroaging, when the degenerative processes begin. Many hypotheses on the multifactorial nature of women's brain aging are elaborated, and tested in high-tech research centers. The most analyzed Alzheimer's disease (AD) is characterized not only by Aβ oligomers and fibrils accumulation, but also by metabolic and inflammatory changes, with the onset during menopausal transition and early years of menopause. Deep analysis of endocrine, neural, and metabolic pathways are giving new insights to the sequential view of Aβ-centric in AD pathogenesis, prevention, and treatment from perimenopause, for maintaining women's neurological health.

High rate complications and recurrences in reconstructive surgery using in situ synthetic/polypropylene (PP) meshes have driven to a new concept based on mesenchymal stem cells (MSCs) for homeostasis repair in pelvic floor disorders (PFD). Prevention and therapy with MSCs are up to date analyzed on small and large animal models, less in women trials. Cell based-vaginal/intraurethral, or systemically introduced, tissue engineering (TE) with new generation meshes/scaffolds MSCs seeded-bone marrow, adipose tissue and recently proposed the endometrial/menstrual MSCs (eMSCs/MenSCs) for PFDs, management. Easy collected, isolated with specific markers, cultured for number harvesting, without ethic and immune compatibility issues, with unique biologic properties eMSCs/MenSCs differentiate in many cellular types—smooth muscle, and fibroblast-like cells, preserving cell shape, and phenotype, without oncogenic risks, and collagen, elastin fibers; eMSCs/MenSCsare appropriate for PFDs management, respecting good protocols for human safety. The quick appeared regenerative effect-mediated by angiogenesis, apoptosis inhibition, cell proliferation, no chronic inflammation and low/no foreign body reactions, less thick collagen fibers, and fibrosis improve connective/neuromuscular tissues; less pelvic structures stiffness with more elasticity are advantages for new meshes/scaffolds generation in TE. Human eSMCs/MenSCs deliver bioactive factors by their exosomes/microvesicles/secretome for paracrine effects to injury site, facilitating in vivo tissue repair.

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Objectives: The objective of this prospective study was to analyze the effect of vaginal micronized progesterone (VMP) daily administrated in women with recurrent pregnancy loss, recurrent miscarriage, and/or preterm birth on neonatal outcomes. Methods:In the treat group patients received 200 mg/day VMP (14 days/month, during the luteal phase) from preconception until completed 36 weeks of gestation. Women from the control group did not receive VPM treatment. Ultrasonographic examination was performed for gestational age confirmation, assessment of cervical length and congenital malformation screening in fetus. Results:Compared with the control group, the women from the VMP group had a decreased time to conception, lower frequency of miscarriages and higher gestational age at delivery. Newborns from mothers treated with VPM had significantly higher birth weight than newborns from the control group of mothers (p = 0.022). The frequency of stillbirths and the need for oxygen supplementation and mechanical ventilation was lower in the newborns from treated group of mother compared with control group. Conclusion:Vaginal micronized progesterone 200 mg/day from preconception to 36 weeks of gestation in women with recurrent pregnancy loss reduced the frequency of miscarriages, stillbirths, preterm births and neonatal morbidity.

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