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ANDROGENS AND PROSTATE CANCER: NOTHING TO FEAR BUT THE FEAR ITSELF
Prof. Alvaro Morales
Centre for Advanced Urological Research, Queen's University,
62 Barrie St., Kingston, Ontario, Canada K7L 3J7. moralesa@post.queensu.ca
The effect of testosterone (T) on the development of the prostate
gland is well documented. The involution of prostate cancer
(PCa) following suppression of circulating androgens is also
well known. Unfortunately, a widespread belief that T produces
PCa has existed for a long time. There is no compelling evidence
for such a causal relationship. On the contrary, early evidence
suggests that it is the T deficiency status that might facilitate
prostate carcinogenesis. The verification for either view,
however, is lacking.
The process of prostate carcinogenesis is not fully understood
although great strides have been made in the last decade.
There is overwhelming evidence that factors influencing the
development and growth of PCa are much more than simply an
excess or shortage of circulating sex steroids: non-steroidal
hormones (insulin, glucocorticoids, leptin, growth hormone),
genetic susceptibility, sexually transmitted agents, diet,
and environmental carcinogenesis appear to be significant
contributors to the process. There is, in addition, a growing
body of literature presenting the puzzling paradox that T
and other androgens are essential for the gland's development,
while they may also prevent and inhibit the establishment
of PCa. There is solid information indicating that novel signaling
pathways, with or without participation of the androgen-receptor
signaling cascade can be activated independently of serum
androgen levels. Finally, intriguing preliminary studies have
shown that the hormonal ecology of the prostate might be independent
of the androgen levels in peripheral blood.
It is widely accepted that the administration of T to a man
with known or suspected PCa is contraindicated. On the other
hand, it should not escape anyone the irony and inconsistency
in therapeutic criteria when men with metastatic PCa are treated
with intermittent androgen suppression, essentially allowing
the restoration of T production. Furthermore, castration (chemical
or surgical) generally does not constitute part of the curative
treatment offered to men with localized PCA.
Experience has shown that a pre-existing PCa might be stimulated
by T and that a T deficiency state may mask the presence of
such a tumor. For this reason, extreme caution should be exercised
in regards to prostate safety when T therapy is contemplated.
Potential adverse effects related to prostate safety can,
thus be detected early, corrective action taken promptly and
serious sequelae avoided.
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