Progesterone For Brain Health

You might be surprised to learn the significance of progesterone for brain health, but it can play a role in brain regeneration after illness or injury. Most people associate progesterone exclusively with female hormones, but it has a myriad of different functions relative to the brain. In fact, one study in the Frontiers in Neuroendocrinology journal states:

“Emerging data indicate that progesterone has multiple non-reproductive functions in the central nervous system to regulate cognition, mood, inflammation, mitochondrial function, neurogenesis and regeneration, myelination and recovery from traumatic brain injury.”[i]

One of the major mechanisms of these activities is via progesterone’s ability to function as a neurosteroid, a naturally occurring steroid that is produced within the body and functions to alter neural excitability. Cells in the brain, spinal cord and peripheral nervous system can all synthesize progesterone from cholesterol, and progesterone is able to access the brain and nerves to bind to progesterone receptors in the brain.

Certainly, in pregnancy, rising progesterone levels serve to offer protection to the fetus from neural excitation that could be damaging to his or her fragile nervous system. In a similar fashion, there appears to be a reduction in seizure activity following traumatic brain injury with progesterone supplementation, indicating a similar mechanism of calming neural excitation.

There has been significant research done over time to assess the role of progesterone in recovery from traumatic brain injury. Results have certainly been mixed, but there is significant data to show that progesterone has a neuroprotective effect. In one clinical study known as ProTECT II, 100 patients with moderate to severe traumatic brain injury were assessed.[ii] One group was given the standard treatment for traumatic brain injury while the other was given that same treatment plus three days of intravenous progesterone (the dose was sufficient to create levels that were triple those seen at the end of pregnancy). The mortality rate in the conventional treatment was 33%, and the mortality rate in the group who received progesterone was 13%.

One of the major ways progesterone helps after a traumatic brain injury is by reducing edema in the brain. It does this by inhibiting the expression of the genes that trigger cells to release the inflammatory cytokines that lead to the swelling and edema. It also influences water channels in the brain, allowing the outflow and relieving the pressure of excess fluid. It also inhibits programmed cell death (apoptosis) by upregulating the genes that influence it, thus sparing cells that might otherwise be killed off.

Another of the mechanisms of progesterone’s neuroprotective and regenerative effects is by promoting myelination. Similar to B12, lion’s mane and acetyl-L-carnitine, progesterone can help support healthy myelination of nerves promoting their growth and repair after damage.

Some generalized studies exist on the effect of progesterone on cognition. One such study demonstrated a correlation between progesterone levels and cognition in post-menopausal women.[iii] The researchers looked at the data of 643 healthy post-menopausal women, ranging in age from 41 to 84, who were part of the Early Versus Late Intervention Trial with Estriol (ELITE) study. They conducted neuropsychological tests to assess cognition and memory. No correlation was found between estrogen and cognition, but a correlation was found between progesterone and cognition, with better outcomes on verbal memory tests and global cognition.

Certainly progesterone can be of benefit to women in terms of balancing hormones, but it seems there are many benefits to the brain as well. These neurological benefits would apply equally to men and women, and could be important for those with traumatic brain injury, and any illness that causes neurological degeneration.

[i] Brinton, R D, et al. “Progesterone receptors: form and function in brain.” Front Neuroendocrinol 29, no. 2 (May 2008): 313-39.

[ii] Wright, D W, et al. “ProTECT: a randomized clinical trial of progesterone for acute traumatic brain injury.” Ann Emerg Med 49, no. 4 (April 2007): 391-402, 402.e1-2.

[iii] Henderson, V W, et al. “Cognition, mood, and physiological concentrations of sex hormones in the early and late menopause.” PNAS 110, no. 50 (December 2013): 20290-20295.