SEATTLE - Word retention drops sharply after only two minutes among men
undergoing testosterone deprivation therapy, according to scientists at
Oregon Health and Sciences University School of Medicine and Cancer
Institute.
This drop in verbal memory happens even though initial learning of the
words, or encoding, is the same for testosterone-deprived and healthy
men.
Members of OHSU's s departments of Behavioral Neuroscience and Medicine
will present their study, called "Androgen ablation impairs
hippocampal-dependent verbal memory processes, " Oct 24 to the Society
for Neuroscience in San Diego.
Men who have undergone testosterone deprivation "are able to encode
these words well, and if I ask them immediately, they can recall them as
easily as non-hormone-deprived men," said Joseph Bussiere, a graduate
student in behavioral neuroscience and the study's lead author. "But
after only two minutes, there's a marked drop-off. When you stretch the
time between encoding and retrieval, that's where the problem lies."
In testosterone deprivation or "ablation," the testicles are surgically
removed or drugs are given to block the production of male hormones,
principally testosterone, that can promote prostate cancer growth. This
common treatment for prostate cancer wipes out most male hormones found
in the body.
Bussiere and Jeri Janowsky, Ph.D., professor of behavioral neuroscience
and neurology, OHSU School of Medicine, say the rapid drop in memory
suggests the lack of testosterone affects the function of the
hippocampus, a curved, elongated ridge in the brain that controls
learning and memory. In fact, Janowsky said, similar deficits - the
ability to encode information initially but forget it quickly - is seen
in individuals with well-known cognitive disorders.
"A colleague looked at (the study results) and said, 'Wow, that looks
exactly like what happens with a lesion in the hippocampus," Janowsky
said. "When others have done studies like this on people who have
hippocampal damage from early Alzheimer's disease or lesions due to
strokes, this is the pattern."
The study examined 30 individuals - 14 men undergoing androgen
deprivation treatment for prostate cancer and 16 healthy, age-matched
men - from the Portland area. Participants were shown lists of words
and, to encode them, were asked to identify whether the words were in
capital or lowercase letters, which requires shallow or "perceptual"
processing, or whether they represented objects that occurred in nature
or were artificially made, which requires deep or "semantic" processing.
Participants were then shown another list containing words they'd just
seen as well as new words and were asked whether they'd seen each word
before. This test was performed at three time intervals: immediately,
after two minutes and after 12 minutes.
Testosterone-deprived men can "immediately get the information in, but
then the hippocampus can't consolidate it and send it off for storage,"
Janowsky said. "When you look at their memory, they're perfectly normal
when they're immediately asked to recall something, but they can't hold
or save the information as well in order to recall it over a retention
interval, over a period of time. They're faster at forgetting."
These results, Bussiere and Janowsky say, point to a negative effect of
testosterone deprivation in the hippocampus, which is responsible for
storing information from the first few seconds on. Both the prefrontal
cortex and hippocampal memory systems commonly show declines with aging
and are associated with problems in attention and memory.
"But for long-term memory, the critical structure is the hippocampus. It
doesn't mean the prefrontal cortex doesn't participate, but it's the
hippocampus that's important for these results. After the information
gets in, the hippocampus and other nearby structures are responsible for
processing and storing it over minutes, to days and weeks," Janowsky
said.
The next step in the research is to use brain imaging to assess the
function of the hippocampus in men on testosterone deprivation therapy,
which will be developed at OHSU's Advanced Imaging Research Center. One
study will look at changes in blood flow in parts of the brain that are
activated during the memory tests, and another will examine the effects
of testosterone deprivation on structures in the brain.
"We can see during each task what parts of the brain are active and how
the two brains (testosterone deprived versus normal ) differ," Bussiere
said.
Janowsky, whose laboratory focuses on how cognition changes with aging,
said healthy older men, on average, have about a 40 percent loss in
their normal levels of testosterone as they age, from the ages of 20 or
30, to 70, but that some men in their 80s can have normal and high
testosterone levels like men half their age.
"This is an important first step in an effort to fully understand how
prostate cancer therapies adversely affect memory and other brain
functions, and to develop therapies that do not produce such undesirable
effects," said Tomasz Beer, M.D., associate professor of medicine and
director of the OHSU Cancer Institute Prostate Cancer Research Program.
Beer was a co-investigator in the effort.
The study is one in a series of ongoing research projects funded by the
National Institute on Aging that examine sex hormones, particularly
testosterone and estrogen, as neuromodulators and their roles in
cognitive function in aging. A study in which Janowsky and Beer
collaborated found that high-dose estrogen can be used as a testosterone
deprivation tool for men with prostate cancer, but that these
testosterone-deprived men showed better memory performance than men
undergoing traditional testosterone deprivation treatment.
Other collaborators on the study included Michelle Neiss, a senior
research associate of behavioral neuroscience, and Beer.

knowledge is power - growing old is mandatory - growing wise is optional    
"Many more men die with prostate cancer than of it. Growing old is
invariably fatal. Prostate cancer is only sometimes so."