Progesterone is an endogenous steroid hormone involved in the menstrual cycle, pregnancy, and embryogenesis of humans and other species.
It belongs to a group of steroid hormones called the progestogens, and is the major progestogen in the body. Progesterone is also a crucial metabolic intermediate in the production other endogenous steroids, including the sex hormones and the corticosteroids, and plays an important role in brain function as a neurosteroid.
Progesterone has been associated with robust positive effects in animal models of traumatic brain injury (TBI) and with clinical benefits in twophase 2 randomized controlled trials. Skolnick et al, investigated the efficacy and safety of progesterone in a large, prospective, phase 3 randomized controlled trial.
A multinational placebo controlled study, in which 1195 patients, 16 to 70 years of age, with severe traumatic brain injury TBI (Glasgow Coma Scale score, ≤8 (on a scale of 3 to 15, with lower scores indicating a reduced level of consciousness and at least one reactive pupil) wererandomly assigned to receive progesterone or placebo. Dosing began within 8 hours after injury and continued for 120 hours. The primary efficacy end point was the Glasgow Outcome Scale score at 6 months after the injury.
Proportional-odds analysis with covariate adjustment showed no treatment effect of progesterone as compared with placebo (odds ratio, 0.96;confidence interval, 0.77 to 1.18). The proportion of patients with a favorable outcome on the Glasgow Outcome Scale (good recovery or moderate disability) was 50.4% with progesterone, as compared with 50.5% with placebo. Mortality was similar in the two groups. No relevantsafety differences were noted between progesterone and placebo.
Primary and secondary efficacy analyses showed no clinical benefit of progesterone in patients with severe TBI. These data stand in contrast to the robust preclinical data and results of early single-center trials that provided the impetus to initiate phase 3 trials. (Funded by BHR Pharma; SYNAPSE ClinicalTrials.gov number, NCT01143064 .) 1).