Effects of medroxyprogesterone acetate on cerebral oedema and spatial learning performance after traumatic brain injury in rats.

BACKGROUND Given after brain injury (TBI), progesterone reduces cerebral oedema and facilitates functional recovery. Progesterone analogues have been synthesized for use in many medical conditions and exhibit different chemical and biological properties. Medroxyprogesterone acetate (MPA) is widely used in clinical practice, but oestrogen/MPA combinations may increase the risk of stroke and cardiovascular disease rather than preventing them. In some conditions, MPA can exhibit pharmacological actions that are different from those of natural progesterone. PRIMARY OBJECTIVE AND HYPOTHESIS: Using laboratory rats, this study assessed the efficacy of MPA to determine whether this progestin and natural progesterone exert similar effects as a treatment after bilateral injury to the frontal cortex. MAIN OUTCOMES AND RESULTS MPA produced a dose-related reduction of cerebral oedema at 48 hours post-TBI but neither 4 nor 16 mg/kg doses of MPA enhanced behavioural recovery. CONCLUSION These findings help to clarify the divergent results from prior positive progesterone studies and the negative MPA clinical trials for hormone replacement therapy. The results can be taken to suggest that the control of cerebral oedema, while clearly desirable, is not the only contributor to progesterone-induced behavioural recovery.