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Menopause. 2012 Jul;19(7):804-11. doi: 10.1097/gme.0b013e31824d1fc4.

Effects of long-term treatment with estrogen and medroxyprogesterone acetate on synapse number in the medial prefrontal cortex of aged female rats.

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  • 1Departments of Psychology, University of Illinois at Urbana-Champaign, Champaign, IL, USA.



The present study investigated the effects of long-term hormone treatment, including the most commonly prescribed progestin, medroxyprogesterone acetate, during aging on synaptophysin-labeled boutons, a marker of synapses, in the medial prefrontal cortex (mPFC) of rats.


Female Long Evans hooded rats were ovariectomized at middle age (12-13 mo) and were placed in one of four groups: no replacement (n = 5), 17β-estradiol alone (n = 6), estradiol and progesterone (n = 7), or estradiol and medroxyprogesterone acetate (n = 4). Estradiol was administered in the drinking water and progestogens were administered via subcutaneous pellets that were replaced every 90 days. After 7 months of hormone replacement, the animals were euthanized, and the brains were stained for synaptophysin, a membrane component of synaptic vesicles. The density of synaptophysin-labeled boutons was quantified in the mPFC using unbiased stereology and multiplied by the volume of the mPFC to obtain the total number.


Animals receiving estradiol and medroxyprogesterone acetate had significantly more synaptophysin-labeled boutons in the mPFC than did animals not receiving replacement (P < 0.03) and those receiving estradiol and progesterone (P < 0.02). In addition, there was a nonsignificant trend for animals receiving estradiol alone to have more synapses than those receiving estradiol and progesterone.


This study is the first to examine the effects of estradiol and medroxyprogesterone acetate during rat aging on cortical synaptic number. Estradiol with medroxyprogesterone acetate, but not progesterone, resulted in a greater number of synapses in the mPFC during aging than did no replacement.

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