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Androgen Deprivation Therapy - What
Method Do Men Choose?
(January 2006)
Androgen deprivation of
prostate cells currently can be achieved by two basic methods: 1)
castration and LHRH analogues, which reduce serum testosterone; and 2)
anti-androgens which block androgen signaling through the androgen
receptor, and are associated with a slight rise in the serum
testosterone. This elevation raises the serum level of estrogen by means
of steroid conversion leading to symptoms of hyper-estrogenemia. Each
method effects its own “side-effect” profile. [The lowering of
intraprostatic DHT by 5-alpha-reductase inhibition will not be discussed
here.]
Two articles report on
the selections men make between these options. The article “Preferences
of healthy men for two different endocrine treatment options offered for
locally advanced prostate cancer”, in Current Medical Research and
Opinion, Sept 2005, reported the choices made by 180 men in the UK who
had no evidence of prostate cancer. They were given a week to
consider the method of delivery and the side effects for these two
equally effective options. Some side effects were shared by both
treatments, although to different extents. For an LHRH agonist the major
listed consequences were: reduced erectile function and sexual interest
in 9 of 10 men and hot flushes in 7 of 10, compared to 2 of 10 and 1 of
10 for high-dose, non-steroidal antiandrogens (NSAA), respectively. Drug
specific side-effects for LHRH agonists were an increased risk of
fractures and osteoporosis, and a loss in all men of physical strength.
Whereas for antiandrogens breast tenderness and pain occurred in 7 of 10
men.
Results: 86% of men
chose NSAA, 7% chose LHRH and 7% could not decide. The main reason for
avoiding LHRH agonist was its method of administration, whereas “those
who chose NSAA therapy cited avoidance of the side effects associated
with the LHRH agonists. This study highlights the importance of a full
disclosure about treatment consequences. Since it was performed in
England, the financial aspects of therapy did not influence the
treatment choice.
The second UK study,
reported in BJU International, Nov. 2005, reported the actual
choices made by 150 men with advanced prostate cancer. A week period was
provided for consideration of the differing side-effect profiles.
Results: 42% chose high-dose bicalutamide; 34% chose an LHRH agonist,
and 24% orchiectomy. When evaluated three months after the initiation of
treatment, the men reported satisfaction with their chosen therapies in
87%, 84%, and 94% respectively. The authors concluded that when men are
provided with full information about treatment options “they are
satisfied with their decision 3 months later.”
Of special note
regarding high-dose Casodex: Unpublished data from the Early Prostate
Cancer trial comparing 150 mg/day of Casodex vs. placebo showed an
increase in deaths in the Casodex arm of the portion of the Scandinavian
study segment which compared Casodex to placebo in a “watchful waiting”
regimen. I queried Dr. Lawrence Klotz, Chief of Urology, University of
Toronto about this issue. He was aware of unsubstantiated information
that the increase was due to cardiac causes, and for this reason the
drug has been de-registered in Canada and Belgium. This issue is in need
of clarification.
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