Progesterone and the Nervous System/Brain

Research Summary

In this emerging area of progesterone research, several research studies attest to the neuroprotective effects of progesterone, an absence of neurological side effects, and a benefit for cognitive function.


Progesterone and the brain

By Margaret N. Groves  Scientific Writer, ZRT Laboratory, Beaverton, Oregon

Many women are familiar with progesterone as a hormone that is essential for fertility and for sustaining a pregnancy.  In fact, the name itself means “promoting gestation.”  Once a woman’s reproductive life begins to wane and she enters perimenopause, progesterone production in the ovaries starts to decline.  By the time she reaches menopause, circulating progesterone levels are so low, they are similar to those normally seen in men.

However, progesterone is far more than a gestational agent. Research is now surfacing which shoes that the benefits of progesterone reach to breast health, cardiovascular health, and nervous system health, most importantly brain function. The rest of this article will take a closer look at just how essential progesterone is for your brain.


Progesterone as a “neurosteroid”

As a result of its critical functions in the nervous system, progesterone has been classified as a “neurosteroid”. It is so essential that it comes from two different places to reach the brain: first, cells in the brain, spinal cord, and peripheral nervous system all synthesize progesterone from cholesterol.  Secondly, progesterone that is circulating in the bloodstream also has direct access to the brain and nerves.

Normal brain function is not the only thing progesterone is required for in the nervous system. An important role of progesterone is to protect the brain from damage and promote repair after injury. It actually does this by promoting the growth and repair of the myelin sheath that protects the nerve fibers.


Progesterone protects the brain from damage after traumatic brain injury

Around 20 years ago, researchers who were studying rats after brain injury made a significant observation.  Female rats which, at the time of the brain injury, were at the stage of their reproductive cycles when progesterone levels were the highest, had significantly less brain damage than male rats or females with lower progesterone levels.  Such research led ultimately to human clinical studies, which have found that high doses of natural progesterone have significantly improved patients’ survival from traumatic brain injury.

One trial, given the name “ProTECT”, randomized intensive care patients with acute traumatic brain injury to either high dose progesterone injections for 3 days or placebo injections.  While all the patients were at a very high risk of death, only 13% of the progesterone-treated patients died of their brain injuries compared with 30% of the placebo-treated patients.

A review published this year suggests that not only should progesterone be used to treat traumatic brain injuries, but that it may also have a role in treating stroke, because of its powerful protective effects on brain tissue. This is a very exciting area of progesterone research, as researchers and clinicians acknowledge the fact that natural progesterone has an excellent safety profile without long term side effects, making it a good candidate for high dose therapy that can also be carried out in a home environment as patients recover.


Progesterone and brain development – smarter kids?

There is published evidence that the children of women who were treated with progesterone during pregnancy showed enhanced development during infancy, achieved better academic results at ages 9-10, and were significantly more likely to attend universities.  While researchers acknowledge that progesterone treatment could not be claimed to promote a new generation of “brainiacs”, the observed benefits can be explained by the fact that it is essential for optimal development of a normal brain in the fetus.  If progesterone levels are too low, normal brain development may be affected, putting an infant at a developmental disadvantage.


Progesterone eases anxiety and facilitates memory

Progesterone naturally metabolizes in brain tissues to the metabolite allopregnanolone, which is known to produce calming, anti-anxiety and possibly enhanced memory effects.  There is some speculation that it could be important in preserving cognitive function in women experiencing the decline in progesterone levels with age.  However, it’s important to note that progesterone is produced by brain tissue itself, and so the reduction in blood progesterone levels as ovarian production decreases may not be as important as other aging processes that have direct effects on the brain’s function.  It will be interesting to see further research on this as aging women increasingly use progesterone in hormone replacement.


Progesterone as a sleeping aid?

Women using an oral progesterone may notice a sedative effect, and doctors usually recommend that the oral form is taken at bedtime (actually, it is often a welcome “side effect” that helps counteract the sleeplessness of perimenopause!)  Basically, there is a large quantity of metabolites produced in the liver after oral progesterone is absorbed by the intestines.  These metabolites have known sedative and hypnotic effects.

On the other hand, women using progesterone cream do not produce metabolites in such large quantities because the progesterone is absorbed through the skin and bypasses the liver metabolism.  However, as stated before, some women may experience progesterone’s calming effect after using it in cream form.


Progestins vs. Progesterone: Same effects?

Synthetic progestins are molecularly different from natural progesterone and therefore do not metabolize to the same compounds as natural progesterone.  They do not show benefits for cognitive or anti-anxiety function.  In fact, they have not been found to have any of progesterone’s neuroprotective properties.  The progestin that has been the most extensively studied and which is commonly used in synthetic hormone replacement therapy, MPA (medroxyprogesterone acetate), has been found to have negative effects on the nervous system and even reduces the beneficial effects of estrogen.


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