Progesterone has long been recognized for its important role in female health. It is commonly used to compensate for the imbalance in progesterone and estrogen and has been clinically beneficial in weight gain, fatigue, loss of libido, depression, headaches, joint pain and mood swings as well as uterine fibroids, menstrual problems, autoimmune disorders, and bone loss. In males, progesterone is used to support prostate health. Over the last several years, however, exciting new research has begun to unveil another potential property of progesterone-protecting the brain.

New studies are showing that progesterone's effects stretch beyond the reproductive and endocrine systems. In fact, researchers now know that progesterone is produced in the brain by neurons and glial cells in the central and peripheral nervous system of both male and females.1

Progesterone is considered a sex hormone and occurs in female mammals at higher rates than in males, although males produce this hormone as well in lesser quantities. Scientists accidentally discovered that it may be helpful in brain function when they noticed that when brain injury was induced in rodents, many female rats experienced no cognitive deficits even though males suffered impaired brain function.

 

Furthermore, gender differences in stroke outcome, with women being protected from cerebrovascular disease more than men, have implicated progesterone, a hormone often associated with females, in brain health.2 This led to a series of experiments with intriguing results.

Progesterone and the Brain
Laboratory data strongly show that progesterone treatment after traumatic brain injury reduces edema, improves outcomes, and restores blood-brain barrier function.3

A new study appearing in the August 2009 Brain Research Bulletin followed up on previous animal studies that demonstrate progesterone (PROG) significantly reduces cerebral edema and enhances functional recovery from traumatic brain injury (TBI) and stroke in several animal models.4

This new study was designed to investigate the inhibitory effects of progesterone on inflammatory response after stroke and the hormone's influence on the structure of the blood-brain barrier (BBB). Researchers administered 8 mg/kg of progesterone by intraperitoneal injection 1 hour and 6 hours after permanent occlusion of middle cerebral artery was induced in rats. Additional injections of 15 mg/kg were administered subcutaneously once per day after the initial dose. The researchers then measured expression of the inflammatory marker tumor necrosis factor-alpha (TNF-alpha). They also measured levels of matrix metalloproteinase-9 (MMP-9). Recent research suggests an active role of MMPs in the development of aortic aneurysm. Excess MMPs degrade the structural proteins of the aortic wall.

The results showed that progesterone reduced levels of the inflammatory marker TNF-alpha and levels of MMP-9. Progesterone also improved markers of brain health and the health of the blood brain barrier.4 This led the study authors to conclude, "Our findings reveal that PROG [progesterone] inhibited the inflammatory response after experimental stroke and mitigated the severity of brain damage, suggesting a role for PROG in the integrity of the BBB [blood brain barrier] and subsequent edema formation following cerebral ischemia."
Another group of researchers replicated a typical human stroke in 24 rats by blocking (occluding) the middle cerebral artery. The researchers then injected 8 mg/kg of progesterone or a control at 1 hour post-occlusion followed by subcutaneous injections at 6, 24 and 48 hours. Progesterone-treated rats showed a substantial reduction (54 percent) in the volume of the infarct compared to controls. In addition, there was a significant improvement in ability to remain on an accelerating rotarod and increased grip strength observed in the rats treated with progesterone compared to controls.5

According to the study authors, "Taken together, these data indicate that PROG is beneficial in one of the best-characterized models of stroke, and may warrant further testing in future clinical trials for human stroke."

Rat models of traumatic brain injury have yielded similar results. Traumatic brain injury (TBI) is one of the leading causes of morbidity and mortality in young people. Researchers recently conducted a study to investigate the inhibitory effect of progesterone on inflammatory response after traumatic brain injury. Progesterone was injected intraperitoneally using rats as a model of traumatic brain injury, and researchers then detected the expression of three inflammation-related factors: nuclear factor kappa B p65 (NFkappaB p65), glial fibrillary acidic protein (GFAP), and tumor necrosis factor-alpha (TNF-alpha). The water content of injured brain was also examined.
The inflammatory markers NFkappaB p65, GFAP, and TNF-alpha were increased in all injured animals. In rats treated with progesterone, however, the expression level of NFkappaB p65 and TNF-alpha were reduced significantly in comparison with vehicle-treated rats. Progesterone also reduced the water content of injured brain and the lesion volume. In addition, progesterone-treated injured rats showed significant improvements in the Neurological Severity Score test, compared with controls.6

The researchers concluded, "Progesterone inhibits the inflammatory response after experimental traumatic brain injury and mitigates the severity of brain damage."
Studies conducted to date indicate progesterone appears to exert its brain-protective effects by protecting or rebuilding the blood-brain barrier, decreasing development of cerebral edema, down-regulating the inflammatory cascade, and limiting cellular necrosis and apoptosis.1

The studies in animals have been so promising that researchers have begun ongoing human trials for progesterone treatment after TBI.3

Although the research published to date has focused primarily on progesterone's effects on blunt traumatic brain injury and strokes, there is evidence that the hormone affords protection from several forms of acute central nervous system injury, including penetrating brain trauma, anoxic brain injury, and spinal cord injury.1

Conclusion
The fact that progesterone has shown such promise in supporting brain damage indicates that it may also be a valuable tool in enhancing general brain health. We believe the most efficient delivery method for progesterone is through the use of a topical cream.

 

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