Onset of estrogen replacement has a critical effect on synaptic density of CA1 hippocampus in ovariectomized adult rats

Objectives: The aim of this study was to evaluate differences between estrogen replacement therapy initiated either 4 or 12 days after ovariectomy on the synaptic density of the hippocampal CA1 field in rats. Design: Female, adult, Wistar rats were ovariectomized bilaterally under ether anesthesia and divided among the following groups: 1) estrogen (conjugated equine estrogen 50 mug in 0.5 mL of propylene glycol, daily, p.o. gavage, for 60 days), starting 4 days after ovariectomy (n = 5); 2) propylene glycol (0.5 mL daily, p.o. gavage, for 60 days), starting 4 days after ovariectomy (n = 4); 3) estrogen (conjugated equine estrogen 50 mug in 0.5 mL of propylene glycol, daily, p.o. gavage, for 45 days), starting 12 days after ovariectomy (n = 3); 4) propylene glycol (0.5 mL daily, p.o. gavage, for 45 days), starting 12 days after ovariectomy (n = 3). At the end of the treatment, the rats were processed for electron microscopy and light analysis. Results: Synaptic density in all of the CA1 strata subjected to evaluation was significantly higher in animals in which estrogen replacement was initiated 4 days after ovariectomy as compared with controls. In contrast, initiation of treatment after a 12-day interval did not result in recovery of synaptic density in any of the CA1 strata and was significantly lower than that of the animals subjected to hormone replacement after a 4-day delay (P < 0.01). Conclusion: The delay for hormone replacement therapy might have critical implications for modulating synaptic density.