Progesterone Therapy & Traumatic Brain Injury
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Every 15 seconds in the USA someone suffers a traumatic brain injury (TBI). There are, on average, 2.8 million incidences each year, more than 60,000 die, and it causes more deaths in men under 35 than all other diseases combined. Long term care costs run as high as 76 billion dollars annually.
For thirty years, fifty substances to treat TBI cases were tested and all failed. In 2006 the first successful trial was published, using IV progesterone. Over three years, 100 TBI patients were studied — some receiving standard care, others also given intravenous progesterone at triple the highest natural pregnancy levels. The progesterone-treated group showed about a 50% reduction in mortality at 30 days, along with better Disability Rating Scale scores and improved recovery. A follow-up randomized trial confirmed this, with mortality falling to 18% in the progesterone group versus 32% on placebo, and improved neurological outcomes for up to six months. These findings were consistent with hundreds of earlier animal studies showing progesterone to be a powerful neuroprotective hormone.
A later Phase III trial failed to confirm the earlier benefits, this appears linked to dosing and delivery — rapid, high-dose IV infusion differs greatly from the body's own gradual, physiological progesterone signalling. The brain itself raises progesterone after injury as a natural defense. Given its enormous, well-documented protective potential — for stroke, MS, spinal injury, and more — this remarkable neurosteroid cannot be dismissed on the strength of one disappointing trial.
Progesterone is not a sex hormone, and it is not exclusively female — it's produced by the ovaries, testes, adrenal glands, the brain, and glial cells, and serves as the precursor to testosterone, oestrogen, cortisol, and aldosterone. It regulates gene expression, supports cell growth, and has strong anti-oxidative and anti-inflammatory effects. It reduces programmed cell death and inflammatory factors that kill neurons after injury, crosses the blood-brain barrier reducing oedema to barely measurable levels, and lowers lipid peroxidation and isoprostane generation. It protects neurons that would otherwise die, spares cognitive and sensory function, and promotes axon regeneration and myelination. Its metabolite allopregnanolone calms the stress response by potentiating GABA. No adverse side effects have been found in TBI studies, and unlike oestrogen, progesterone helps both sexes without disrupting sexual function.