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Men Treated For Prostate Cancer
Have A Decreased Incidence of Dementia
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Richard L. Bowen1, Heather Beaird2, Craig S. Atwood3, Mark A. Smith2, Alfred A. Rimm2
Pharmaceutical Corp., Raleigh, NC, USA; 2Case Western Reserve University, Cleveland, OH, USA; 3University of Wisconsin, Madison, WI, USA.
Years
Probability of Developing Dementia
(Patients Aged 70 to 72 at Time of Procedure)
Cholecystectomy Group
Exclusions
Transurethral Prostatectomy
Group Exclusions
Hypothalamic-Pituitary-Gonadal Axis
Years
Probability of Developing Dementia
(Patients Aged 73 to 75 at Time of Procedure)
Gallbladder
Enlarged
Prostate
Inguinal
Hernia
Age
67-69
1.0
1.8
2.2
2.4
Age
70-72
1.0
1.8
2.1
2.2
Age
73-75
1.0
2.0
2.8
2.9
Email:
Prostate
Cancer
Phone:
Transurethral prostatectomy
Herniorrhaphy
Cholecystectomy
Prostatectomy
5 Year Relative Risk of Dementia
DISCUSSION
This study provides convincing evidence that, regarding
hormones, it is the age-related increase in gonadotropins
rather than the loss of sex steroids that contributes to the
pathogenesis of Alzheimer’s disease. This statement is
based on the fact that more than 10 prospective studies
have failed to demonstrate a statistically significant
association between circulating levels of androgens and
prostate cancer risk. In other words, since there is a clearly
an inverse relationship between prostate cancer and
dementia, but no relationship between prostate cancer and
testosterone, it is unlikely testosterone is playing a direct
role in the pathogenesis of Alzheimer’s disease. The most
common treatment, GnRH agonists, suppresses both
gonadotropins and sex steroids. If the difference in the
rate of dementia seen in this study is due to the GnRH
agonist, its effect would be exceptional. For example,
among the 73 to 75 year age group, if it is assumed that the
59% of patients in the prostatectomy group (whose risk is
shown to be 0.062) really has a risk of developing D/AD
equivalent to that of say, the cholecystectomy group
(0.095). Then the 41% of patients believed to have received
a GnRH agonist would actually have an exceptionally
decreased risk of 0.015 for dementia.
CONCLUSION
At five years, men who underwent surgical prostatectomy
for prostate cancer have approximately half the risk of
developing dementia as men who undergo other common
surgical procedures. Further research is needed to
determine if this difference is due to GnRH agonist therapy.
Phase II clinical trials using the GnRH agonist leuprolide to
treat patients with Alzheimer’s disease are currently
underway and should provide important information as to
its effect.
Alt. Contact (Last, First):
Herniorrhaphy Group
Exclusions
Email:
Prostatectomy Group
Exclusions
Phone:
A serendipitous encounter with a patient has led us to examine the
possibility that hormones of the hypothalamic-pituitary-gonadal axis
other than the sex steroids may directly contribute to the
pathogenesis of Alzheimer’s disease. After he patient received the
gonadotropin releasing hormone (GnRH) agonist leuprolide acetate a
common hormonal treatment for prostate cancer, his wife noticed an
improvement in his cognitive function which subsequently remained
stable for more than five years. To ascertain whether treatment with
GnRH agonists such as leuprolide has a beneficial effect in
Alzheimer’s disease, an epidemiological study was performed. The
study was designed to determine the incidence of dementia in men
who underwent prostatectomy for prostate cancer and would have
likely received a GnRH agonist (it is estimated that approximately 40%
of prostatectomy patients will experience disease recurrence and
undergo GnRH agonist therapy). All in-patient Medicare hospitalization
claims for men aged 67 to 75 during the years 1984 through 1997 were
analyzed and the incidence of dementia in men who underwent
prostatectomy for prostate cancer (n=139,414) was compared to three
control groups who would not have received GnRH agonist therapy.
The control groups included men with; gallbladder disease who
underwent cholecystectomy (n=255,493), inguinal hernia who
underwent herniorrhaphy (n=162,115), and benign prostatic
hyperplasia who underwent transurethral prostatectomy (n=635,615).
The cohorts were separated into three groups based on their age at
the time of the procedure; A) 67-69, B) 70-72, and C) 73-75. The
prostate cancer group was designated the reference group with a risk
of developing dementia of 1.0 At five years post-procedure, the
relative risk of dementia for men with BPH was 2.2, 2.1, and 2.8 for age
groups A, B, and C respectively. For men with gallbladder surgery the
risk was 1.8, 1.8, 2.0 and for the hernia group it was 2.4, 2.2, and 2.9.
Along with our other findings, these results lend further support to the
premise that gonadotropins promote the development of AD and that
GnRH agonists are a potential therapeutic agent for its treatment.
Clinical trials using leuprolide acetate in the treatment of mild to
moderate Alzheimer’s disease are currently underway.
Probability of Developing Dementia
(Patients Aged 67 to 69 at Time of Procedure)
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ABSTRACT
Name (Last, First):
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