The interplay between sex hormones and brain plasticity across the lifespan

Abstract Background Sex hormones including estrogen, progesterone, and testosterone, can significantly influence brain plasticity and cognitive function across the lifespan in human beings. Hormonal fluctuations during puberty, adulthood, menopause and aging affect neurogenesis, synaptic remodeling and learning. These dynamic endocrine changes contribute to sex-specific differences in cognition and may underlie differential susceptibility to neurodegenerative disorders. This paper presents a narrative literature review of this topic. Methodology A narrative literature review was conducted using PubMed and related electronic databases. Experimental animal studies, in vitro research, and human clinical and observational studies examining the effects of sex hormones on neuroplasticity and cognition were included. Outcomes assessed included molecular markers of plasticity, neurogenesis, and behavioral measures of cognitive performance across different life stages. Results Estrogen was found to enhance synaptic plasticity, dendritic spine density, neurogenesis, and hippocampal-dependent cognition through genomic and non-genomic mechanisms. Progesterone exhibited context dependent effects, supporting neuroprotection and synaptic modulation, with cognitive outcomes influenced by timing and interaction with estrogen. Testosterone and other androgens promoted hippocampal neurogenesis, synaptic maintenance, and spatial cognition via androgen receptor signaling and local conversion to estrogen. Age related declines in sex hormones were associated with reduced neuroplasticity and subtle cognitive impairment, particularly after menopause and during male aging. Conclusion Sex hormones are key modulators of brain plasticity and cognition throughout life. Hormonal decline with aging is associated with reduced neuroplastic capacity and cognitive changes. Timely and targeted hormonal interventions may support brain health, though further long term studies are required.