FEATURED ARTICLE: Testosterone: Does Testosterone Kill Brain Cells?
In late September last year news wires around the world described research conducted at Yale University. The gist of the story was that exposure to
testosterone led to a series of events that culminated in the death of neurons, or brain cells. Those who read the details of the study found that
the effect resulted only from large doses of testosterone, similar to what athletes-including many bodybuilders-administer to themselves. Lead
researcher Barbara Ehrlich, Ph.D., a professor of pharmacology and physiology at Yale, was quoted as saying, "Next time a muscle-bound guy in a sports
car cuts you off on the highway, don't get mad. Just take a deep breath and realize that It might not be his fault."
The results of that study initially seem alarming. Does It mean that those who use large doses of testosterone are facing a future of dementia? If
that's true, why aren't there already athletes, many of whom used large doses of testosterone years ago, experiencing obvious mental decline?
Testosterone affects various regions of the brain, including the hippocampus, preoptid area, amygdala and medial hypothalamic areas. When secreted
in normal amounts or when testosterone blood levels are within the normal physiological range, testosterone is beneficial for brain function. Indeed,
various studies show that men who have low testosterone levels have a higher incidence of degenerative brain diseases, including Alzheimer's. A
just-released study found that middle-aged men low in testosterone are more prone to mental depression.
According to the results of the new Yale study, however, when brain neurons are exposed to higher-than-normal levels of testosterone, a cellular process
is initiated that results in the death of neurons. The process, known as apoptosis, amounts to cellular suicide. In the case of testosterone, when neurons
are exposed to normal levels of testosterone, calcium ions enter the brain cells in an oscillating fashion; that is, the amount of calcium that enters the
cell varies. When the neurons are exposed to higher levels of testosterone, however, a continuous high cascade of calcium enters the cell, which acts as
a signaling device that turns on the process of cellular death.
The neuron-suicide scenario occurs in many degenerative brain diseases. The researchers also used estrogen but found that it had no adverse effects on
brain cells.
Several aspects of the study must be considered. For one thing, it used an in vitro, or test-tube-isolated cell, protocol. It also used neuroblastoma cells,
which are derived from a type of brain tumor and which are used in preference to normal neurons because they react more to stimuli than normal brain cells.
The isolated tumor cells were exposed to elevated testosterone levels for six to 12 hours.
In order to get into the brain, testosterone must pass through the protective network of blood cells known as the blood-brain barrier. Testosterone can pass
through the barrier to some extent because it is lipid-soluble.
One pertinent question is whether normal brain cells would react in a similar way. Does what occurs in an isolated tumor cell exposed to high levels of
testosterone for up to 12 hours also happen in the human body? The authors suggest that the effect is cumulative, meaning that the loss of brain neurons
would likely not become apparent for many years.
Another aspect to consider is that athletes use other substances that may counter the effect of testosterone on brain cells. Growth hormone and insulinlike
growth factor 1, for example, are known to protect neurons. In fact, IGF-1 prevents apoptosis.
How much testosterone, for how long, is required to kill neurons? Does it take years of consistently using larger-than-normal doses? Since the Yale study
showed that estrogen not only doesn't cause neuron death but may offer some protection, that's another factor to consider. Testosterone is converted in the
brain into estrogen- would that he enough to counter the negative effects of elevated testosterone on neurons?
The authors imply that the testosterone neuron death effect is so potent that it would be immediately apparent in some people. Very well-who would such people
be? Someone with prior brain damage? Because the study raises more questions than it answers, it must be considered preliminary. Clearly, further research is
necessary before ultimate conclusions can be drawn about the effects of high levels of testosterone on brain cells.
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