Low Testosterone- The Smoking Gun of Brain Disorders (study shows sudden drop in Testosterone can induce Parkinson’s symptoms)

conanLow Testosterone is far more prevalent than once appreciated. Traditionally thought of as a condition of old age in men (30% of men over 75 have low testosterone by age related standards and likely 100% are low relative to optimal levels for a 20-30 year old), we are now finding low testosterone in teenagers and young adults. In men this condition is called hypogonadism and is divided into two categories:

1. Primary Hypogonadism– This is where the testes have failed and the problem originates in the testes (Klinefelter, undescended testes, injury to the testes, or damage from chemotherapy or mumps infection).

2. Secondary Hypogonadism– This is where the testes function normally but they are not getting the signal from the hypothalamus-pituitary (H-P) to produce testosterone (Kallmann, tumors, inflammatory disorders, medications like opiates, alcohol, THC,  normal aging, stress).

This article by Khasnavis et. al., “Castration Induces Parkinson Disease Pathologies in Young Male Mice via Inducible Nitric-oxide Synthase”, presents key findings describing a mechanism by which low testosterone can cause brain damage. Co-author Pahan is quoted as saying “In men, testosterone levels are intimately coupled to many disease processes…therefore, preservation of testosterone in males may be an important step to become resistant to Parkinson’s disease”.

The key finding in this study was that low testosterone induced an increase in Nitrous-Oxide synthase with a resulting increase in Nitrous Oxide that leads to cell death within the brain.  There was a decrease in GDNF (Glial-Derived Neurotrophic Factor) with resulting specific loss of tyrosine hydroxyls positive neurons in the nigra area of the brain and loss of tyrosine hydroxyls positive fibers and neurotransmitters in the striatum. They created these conditions by castrating mice with the resulting low testosterone condition having those effects listed, along with increases of glial fibrillary acidic protein, increased CD11b, and increased alpha-synuclein. 

“This study has become more fascinating than we thought,” said Pahan. “After castration, levels of inducible nitric oxide synthase (iNOS) and nitric oxide go up in the brain dramatically. Interestingly, castration does not cause Parkinson’s like symptoms in male mice deficient in iNOS gene, indicating that loss of testosterone causes symptoms via increased nitric oxide production.”

Brain symptoms have been known to be associated with hypogonadism for over 60 years, as shown here. Werner, in 1939, under the term male climacteric, described “nervousness, psychological depression, impaired memory, inability to concentrate, fatigue, insomnia, hot flashes, periodic sweating, and loss of sexual vigor as symptoms of low testosterone. 

Zarrouf et. al. “Testosterone and depression: systematic review and meta-analysis” published in J. Psychiatric pract. July 2009, showed that seven studies that were placebo-controlled, double blind in design, showed a positive effect of testosterone therapy for depression with a P=0.0001 (highly significant). 

The work that remains to be done to completely figure out this challenge is in determining the causes of low testosterone beyond the obvious ones listed in this article.  There clearly must be environmental toxins that are suppressing the H-P axis. Will it end up being the BPA and plastics, pesticides and herbicides, persistent organic pollutants (POP’s), heavy metals, aspartame with it’s conversion to formaldehyde in parts of the body, or some other yet to be defined toxin, nutrient deficiency or all of the above?

Dr. Paul

 

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