Androgen deprivation therapy
(ADT) is a form of chemical castration that is prescribed to eliminate
testosterone in men with advanced prostate cancer because the disease
is fueled by testosterone. It is widely used and so effective at
halting the progress of the cancer that men are often treated with ADT
for many years.
Cognitive impairment is a known side effect of declining
testosterone, in general, so it is naturally of concern with ADT.
‘The use of androgen deprivation therapy to treat advanced prostate cancer is not associated with an increased risk of Alzheimer disease.’
A large-scale, population based study led by Dr. Laurent Azoulay,
Senior Investigator with the Lady Davis Institute at the Jewish General
Hospital, has concluded that the use of androgen deprivation therapy to treat advanced prostate cancer is not associated with an
increased risk of Alzheimer disease.
This result, published in the Journal of Clinical Oncology
and accompanied by exclusive coverage by the American Society of
Clinical Oncology (ASCO) is important because it soothes fears raised by
an earlier, very controversial study that asserted a significant and
Dr. Azoulay, an Associate Professor of Epidemiology and
Oncology at McGill University, explained, "However, there is a significant
difference between cognitive limitations and the biological mechanisms
associated with dementia."
Dr. Azoulay and Farzin Khosrow-Khavar, a McGill University doctoral
candidate under his supervision, discovered some troubling
methodological deficiencies in the studies that found the association.
Thus, they undertook to study a cohort of nearly 31,000 men who were
newly diagnosed with nonmetastatic prostate cancer over a twenty-seven
year period from the United Kingdom's Clinical Practice Research
Datalink, one of the largest data bases of its kind.
"Our group was alarmed to see the earlier study that proposed that
ADT doubled the risk of Alzheimer disease," said Dr. Azoulay. "Such a
dramatic finding called for further investigation and we found some
important methodological problems in the study. Because ADT is so often
given to older men, very careful statistical analysis is required to
assert a causal relationship. Once we applied the correct methodology we
found no statistically significant association. However, we would
encourage additional studies to confirm our findings."
ASCO was quick to highlight Dr. Azoulay's study because of its
immediate clinical importance. It wanted to make sure that clinicians
who may have become reluctant to prescribe ADT in light of the contrary
finding were reassured that the causal link was not supported by the
"For most every medication there is a judgment to be made between
its intended purpose and possible adverse effects," point out first
author Khosrow-Khavar. "There are coping mechanisms to compensate for
anticipated issues with cognition. But, if patients believed that ADT
doubled their risk of Alzheimer disease they may be reluctant to take it
for their cancer. Thus, our analysis should be welcome news for men
whose prostate cancer is being controlled with ADT."