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Introduction
Estrogen initiates or mediates an impressive array of biological functions, with receptors in a multitude of tissues and cell types. The presence of estrogen receptors throughout the brain-hypothalamus, pituitary, hippocampus, cerebral cortex, midbrain, and brainstem-implicates estrogen as an effector for multiple neurocognitive processes.[1] Cumulative evidence has confirmed that gender resides in the nervous system as well as the reproductive system. Estrogens act on the central nervous system (CNS) at the genomic level and beyond, modulating neurotransmitter production and action, influencing electrical excitability and synaptic function, and changing the morphological features of neural elements involved in function.[2]
Effects of Estrogen on Neurological Function
Estrogen and other gonadal steroids are now known to be among the most powerful biologic influencers of the CNS[3], exerting both neurotropic and neuroprotective effects as well as influencing other parameters of mental function. (Table 1) Brain aging is thought to be an imbalance between neuronal injury and repair.[4-6] Estrogen is known to stimulate production of nerve growth factors which induce growth of neurons, preserve viability of existing neurons, and effect repair of those neurons that are damaged.[4]) Estrogen receptors have been observed to colocalize with neurotrophins in the rat forebrain, indicating that estrogen may play a considerable role in the development and maintenance of neural substrates of cognition[7]; estrogen is known to interact with multiple neurotransmitter systems.[8]
Estrogen also influences overall brain function through affecting blood supply. The brain is very heavily vascularized (one-third of brain volume is blood vessels) and completely dependent upon blood flow for proper function.[3] Doppler ultrasound in both the cerebral and the carotid arteries found a significant correlation between the pulsatility index (an indicator of decreased blood flow to the brain) and months since menopause, independent of age.[9] Estrogen replacement therapy (ERT), however, was able to reverse blood flow impedance.[10] Estrogen also has anti-inflammatory properties which protect against cardiovascular disease.[11;12]
Estrogen and Mental Processing over A Woman's Lifetime
Estrogen influences mental function from the earliest stages of human development. Estrogens are critical elements in the imprinting of gender on a developing fetus[2] through differing exposure to sex hormones in utero, which induces gender-specific wiring that will later be activated by gonadal steroid surges at puberty.[1]
The onset of hormonal cycling at puberty has long been...