Testosterone and Your Brain
Most hypogonadal men that go on HRT (testosterone therapy) expect it to ramp up
their libido and erections almost right away. However, what happens more
often is that the testosterone first affects their brain. I remember when
I went on pellets, which got my testosterone levels up near 600 or 700. I
noticed my (mild) anxiety and dysthymia improving significantly. And, when
I went on testosterone cypionate, which boosted my testosterone further still, I
could feel it right between the ears. The evening of my first shot I
told my wife that it felt like my brain was being rewired. It took a few
days for morning erections to begin and libido to rise. But the brain
boosting benefits came right away.
So let's look at some of the key brain changes that researchers have noticed
relating to testosterone:
1. Dopamine. Testosterone's most pleasurable effect on the brain
has got to be it's dopamine-boosting powers. In my link on Testosterone and Dopamine,
I document how there are key parts of the brain that are heavily dependent on T
to boost dopamine and that dopamine is one of the keys for one's sex life.
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Researchers have increasingly found that dopamine is
also a huge key in fighting
depression.  Many men have used Buproprion (Wellbutrin/Zyban) to overcome
depression due its unique abilities to often help sexual function. How
does Wellbutrin work? One of its modes of action is boost dopamine in
certain important brain regions. Gotta have it!
2. Acetylcholine. Testosterone appears to boost acetylcholine, the
"memory neurotransmitter" as well. One study noted that "gonadectomy
selectively reduces acetylcholine in the hippocampus."  So low testosterone is
not just hard on your sex life - it's hard on your brain!
NOTE: As a side note, this testosterone boost of acetylcholine is also
probably good for your erectile strength. Acetylcholine is kind of "Nitric
Oxide Lite" and helps with vasodilation. One animal study showed that
testosterone boosted acetylcholine in the levantor ani muscle, which is part of
your all-important pelvic musculature. 
3. Hippocampal Neurogenesis. Hippo what? Researchers recently
found that exercise actually created new cells in the rat hippocampus, which is
the center of memory.  The hippocampus is attacked by the plaques and
tangles of Alzheimers for example.  Of course, this is HUGE and is
an example of the "plasticity" of the brain and its ability to at least
partially rebuild itself.
Okay, so exercise can rebuild the hippocampus. But what does that have to
do with testosterone? Well, it turns out that testosterone plays an
indirect role. Exercise boosts brain levels of testosterone - some of which is
converted (via 5-alpha reductase) into DHT - and it is DHT which is responsible
for the neurogenesis.
4. Vasopressin. Oxytocin's lesser known cousin, vasopressin
regulates scores of activities in the body, including blood pressure,
post-orgasmic response, memory and the CNS (central nervous system).
Researchers have noted that rats lose their vasopressin-related nerve fiber in
certain parts of their CNS when testosterone is lowered. And, when
testosterone is restored, the nerve fiber density in these regions is restored.
 This is yet another example where adding testosterone to a deficient animal is like watering a flower: whatever is wilted and about to die
comes back completely to life. (Venous Leakage is yet another example.)
5. Memory. Many studies have shown that testosterone improves working memory in men.
And working memory is ground zero for just about everything that you do in your brain. Almost anything
that needs to be processed has to go through working memory before it is analyzed, stored or synthesized
by other parts of the brain. Other studies have shown that visual and verbal memory improve in men
given testosterone.  No wonder that many hypogonadal men complain of "mental fog". Part of this may
be due to testosterone's ability to stimulate acetylcholine, the "memory neurotransmitter" mentioned in
6. Cognition. Yes, even your ability to think is affected profoundly
by testosterone. Studies, for example, have shown that testosterone
increases spatial processing power in both young and older men. 
So, if you're looking for a nootropic AND you happen to be low T, testosterone
may be your answer. It's ability to improve many types of memory and
increase cognition is hard to beat. In fact, some executives are now going on HRT just
because of its brain-boosting abilities. See my link
on Testosterone for Executives
in the Peak Testosterone Forum for more information.
NOTE: According to one study, DHT did NOT improve working memory.  That is suprising considering
its powers over the hippocampus mentioned in #3.
One of our biggest health problems is depression. This afflicts tens of millions of men worldwide every year.
Of course, the standard treatment for years was to throw truckloads of SSRI's at the problem, which have had
tepid results at best. However, researchers are finally recognizing that in men with lowish testosterone, HRT
can often greatly help. One meta-analysis found that "TT may have an antidepressant effect in depressed patients, especially those with hypogonadism or HIV/AIDS and elderly subpopulations."
What is remarkable is that this study was willing to go on record and state that
"the route by which TT [testosterone] is administered may play a role in
treatment response." in other words, they actually admitted that testosterone
can have a place in proper treatment of depression (in men with low or lowish
T). For more information, see my link on
Testosterone and Depression.
8. Anxiety. Hypogonadism and high anxiety very often go together as I
show in my link on
Testosterone and Anxiety.
9. Gherlin. Gherlin is famous as the "Appetite Hormone" but could just as
easily be thought of as a Brain Hormone because it plays such a pivotal role in
the health of your key memory brain structure, the hippocampus. It turns out that
being low testosterone leads to low gherlin levels and HRT (testosterone
therapy) restores gherlin levels to baseline. See my link on Testosterone and Appetite for more information.
CAUTION #1: According to famed oxytocin researcher Paul Zaks, testosterone is
an oxytocin inhibitor.  Of course, oxytocin is the "Bonding, Empathy and
Generosity Hormone" and so, according to his research, increasing testosterone
could make one less empathetic, which obviously is not a good thing. I
think one has to be cautious with jumping to conclusions here for men with
reasonable testosterone levels. There is also considerable research that
shows that it is the low testosterone males that are anxious and more likely to
fight and be aggressive. It does point out, though, that more not always
One thing I have wondered, though, if this oxytocin-inhibiting property of
testosterone is not partially ameliorated by the fact that, at least in animal
studies, testosterone increases oxytocin binding.  One study even noted
that castrated animals lost their oxytocin receptors in certain key brain
regions and restoring testosterone brought back oxytocin receptors to youthful
levels.  Oxytocin may also have a dark side: researchers have found
that it can increase envy and gloating.
CAUTION #2: One can make the argument that testosterone should be ramped
up slowly rather than starting high and "seeing what happens" as is almost always the case.
An example of this was one of our posters on The Peak Testosterone Forum
that experienced an almost manic episode after going on testosterone pellets. This is a rare reaction, but
it probably ties back to testosterone's brain-boosting abilities. If a man is hypogonadal and suddenly triples his
testosterone through HRT, that's a lot of adjustment for the brain to handle in some cases all at once.
1) Fundamental & Clinical Pharmacology, Dec 2004, 18(6):601-607,
"Dopamine, depression and antidepressants"
Trends in Cognitive Sciences, Feb 2006, 10(2):77–82, "Thinking with your gonads:
testosterone and cognition"
Journal of Neurobiology, Mar 1982, 13(2):153–161, March 1982"Testosterone
increases acetylcholine receptor number in the “levator ani” muscle of the rat"
5) Neuroendocrinology, 1989, 50:199–203, "Testosterone Modulates Oxytocin Binding
in the Hypothalamus of Castrated Male Rats"
6) Brain Research, Feb 1998, 1(23):167–170, "Region-specific effect of
testosterone on oxytocin receptor binding in the brain of the aged rat"
8) Brain Research, Mar 1990, 511(1):129–140, "Gonadal steroids regulate oxytocin
receptors but not vasopressin receptors in the brain of male and female rats. An
9) Brain Research, Nov 1988, 473(2):306–313, "Testosterone supplementation
restores vasopressin innervation in the senescent rat brain"
10) Journal of Cognitive Neuroscience, May 2000, 12(3):407-414,"Sex Steroids
Modify Working Memory"
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nonaromatizable dihydrotestosterone, improves working memory and alters nerve
growth factor levels in aged male rats"
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13) Aging Male, 2006 Dec, 9(4):195-9, "Testosterone and the brain"
14) Arch Gen Psychiatry, 2006 Feb, 63(2):161-7, "Increased hippocampal plaques
and tangles in patients with Alzheimer disease with a lifetime history of major
15) Proc Natl Acad Sci U S A, 2012 Aug 7,109(32):13100-5, "Mild exercise
increases dihydrotestosterone in hippocampus providing evidence for androgenic
mediation of neurogenesis"
16) Journal of Psychiatric Practice, Jul 2009, 15(4):289-305, "Testosterone and
Depression: Systematic Review and Meta-Analysis"