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Androgen Deprivation and Memory Loss.
(April 2006)
Research conducted by Dr.
Tomasz Beer and colleagues have documented a consequence of androgen
deprivation that may often be too subtle to be detected in clinical
practice in individual patients - that testosterone deficiency is
associated with memory impairment. Their study, “Testosterone Loss and
Estradiol Administration Modify Memory in Men”, J Urol. Jan 2006, used a
battery of tests to evaluate memory in 18 men on androgen deprivation
therapy (ADT), 17 men on ADT combined with transdermal estradiol, and 17
healthy control subjects. All men on ADT had serum testosterone levels of
< 50 ng/dl.
There is a sound biologic
basis for this finding. The cortical centers that process memory - the
prefrontal cortex and the amygdala and hyppocampus - are rich in sex
steroid receptors, and alterations in steroid levels might be expected to
affect neurophysiological function. Studies have shown that “gonadectomy
results in a 40% or greater reduction of synaptic spine density in the CA1
region of the hyppocampus in male monkeys and rats, and androgen
replacement restores synapse number to pre-gonadectory levels in male
rats”. Adverse consequences of ADT have previously been reported in
prostate cancer patients which “decrease memory, attention or executive
function”.
Beer’s research assessed
immediate and delayed verbal memory by testing the subjects’ recall
immediately after two paragraphs were read to them, and then testing again
30 minutes later. Cognitive tests and Profile of Mood State assessment
established that ADT was associated with greater confusion, fatigue,
depression, and decreased vigor compared to the healthy controls. Another
assessment indicated that the men on ADT exhibited a “slower processing
speed”, although tests of working memory found no significant difference
among the three groups. The concomitant exposure to estrogen did not
ameliorate the adverse effects of ADT. Since the study was small, the
authors acknowledge that confirmation would strengthen and clarify their
findings.
Their
conclusion: “Thus, long-term androgen deprivation therapy has the
potential to significantly affect cognition with particular effects on
memory”. Their recommendation: When ADT is an option the “potential for
cognitive toxicity of treatment should be considered in the risk-benefit
calculation”.
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