Reduced Metabolites Mediate Neuroprotective Effects of Progesterone in the Adult Rat Hippocampus. The Synthetic Progestin Medroxyprogesterone Acetate (Provera) Is Not Neuroprotective

This study demonstrated that progesterone was neuroprotective in the hippocampus of ovariectomized rats exposed to kainic acid, an excitotoxic agent, by increasing levels of its metabolites, 5α-dihydroprogesterone (DHP) and 3α,5α-tetrahydroprogesterone (THP). The neuroprotective effect was abolished when the conversion of progesterone to these metabolites was inhibited, indicating their necessity in mediating protection. In contrast, the synthetic progestin medroxyprogesterone acetate (MPA, Provera) did not increase DHP and THP levels and failed to prevent neuronal loss, highlighting the importance of progesterone's natural metabolic pathway for its neuroprotective properties.