Progestins inhibit the neuroprotective effects of estrogen in rat hippocampus.

Although estrogen has beneficial actions in brain, recent clinical trials demonstrated adverse neural effects of hormone therapy in postmenopausal women. The cause(s) of this disconnect between experimental and clinical findings may include unanticipated effects of progestins. We report that both natural progesterone and the clinical progestin medroxyprogesterone acetate block estrogen neuroprotection. These findings underscore the need to evaluate neural actions of progestins in the rational design of hormone therapy.