<p>Aging women experience a significant decline of ovarian hormones, particularly estrogen, following menopause, and become susceptible to cognitive and psychomotor deficits. Although the effects of estrogen depletion had been documented in the prefrontal and somatosensory cortices, its impact on somatomotor cortex, a region crucial for motor and cognitive functions, remains unclear. To explore this, we ovariectomized young adult female rats and fed subsequently with phytoestrogen-free diet and studied the effects of estrogen depletion on the somato-sensory and motor cortices. Low serum estrogen was confirmed prior to biochemical and morphological analyses. Results revealed that estrogen depletion differentially affected the two cortical areas: all three estrogen receptors were downregulated in the somatosensory cortex, whereas in the somatomotor cortex, G-protein-coupled estrogen receptor 30 was upregulated, estrogen receptor α decreased, and estrogen receptor β remained unaffected. Intracellular dye injections revealed decreased dendritic spines on layer III and V pyramidal neurons of the somato-sensory cortex but increased in those of the motor cortex. These were accompanied by decrease and increase of excitatory postsynaptic density protein 95 respectively. Since dendritic spines receive excitatory inputs, these findings suggest that estrogen depletion changes the excitatory connectivity of the somato-sensory and motor cortices in opposite directions. Notably, estradiol replenishment reversed the dendritic spine increase in the somatomotor cortex, confirming the estrogen dependency of this effect. The differential influence of estrogen depletion on these two cortices could have contributed to the cognitive and psychomotor abnormalities in postmenopausal females.</p>