الفهرس 
PathogenesisofCancerProstate
Androgenreceptorstructure.Only 14 pages are availabe for public view
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Abstract
In males, androgens are synthesized by the testes and by the
adrenal gland. The testes are the major source of
testosterone, while the androgens produced by the adrenal
gland are hormone precursors that are enzymatically
converted to testosterone and dihydrotestosterone in prostatic
and peripheral tissues.
Huggins and Hodges first established the role of
androgen deprivation therapy (ADT) in prostate cancer in the
early 1940s, resulting in the award of the 1966 Nobel Prize in
Physiology or Medicine. They demonstrated that, in a patient
with advanced PCa, surgical castration delayed tumour
progression. Soon thereafter, it was learned that
administration of estrogens, with central suppression of
luteinizing hormone releasing hormone (LHRH) and
peripheral production of testosterone, was an equally
effective form of hormonal therapy. Early ADT indeed has a
survival advantage over delayed ADT. Also early ADTallow
PCa patients to avoid complications such as obstructive
voiding symptoms, obstructive renal failure, and pain. The
cost to the patient for the use of early therapy has been the
well-established long-term side effects of ADT, including
sexual dysfunction, cognitive changes, lethargy, bone
demineralization, and metabolic syndrome. The
disadvantages of ADThave led researchers to search for
strategies to reduce negative treatment effects and to improve outcomes. Intermittent androgen suppression seems to be
emerging as one such strategy.
The first clinical report of the use of IAD was authored
by Klotz et al. in 1986. They reported that withdrawal of
diethylstilbestrol from patients with metastatic PCa after
initial clinical response led to a reduction in the side effects
Treatment was reinitiated after the patients became
symptomatic again, and all patients experienced a rapid
clinical response to treatment.
Androgen deprivation achieved by luteinizing
hormone-releasing hormone (LHRH) with or without an
antiandrogen is expensive. Many patients are now being
diagnosed with early or progressive disease on the basis of a
rising PSA level alone, and hormonal therapy is being
employed earlier in the course of disease. As a consequence,
many patients are being treated with hormonal therapy at the
asymptomatic stage and, by virtue of the natural history of
the disease, survive for years after diagnosis.
Hormone therapy given intermittently (with breaks)
has proven to be as effective as hormone therapy given
continuously in asymptomatic men with rising PSA levels
after prostate cancer treatment, Hormone therapy also called
androgen deprivation therapy is designed to block
testosterone from stimulating the growth of hormonedependent types of prostate cancer. Because continuous
androgen deprivation therapy produces side effects such as
osteoporosis, hot flashes, and loss of libido, and because many prostate cancers eventually become resistant to
hormonal therapy, researchers continue to explore
alternatives. Intermittent hormone therapy is an alternative
method of delivering treatment. With intermittent treatment,
men receive hormonal therapy until they achieve a sufficient
treatment response and then they take a break and have a
period of no treatment. The cycle is repeated as needed.
Intermittent hormone therapy may reduce side effects and
delay hormone resistance.
There isevidence that IAD is “non-inferior” to
continuous androgen ablation in terms of time to progression
and overall survival, and evidence is accumulating to suggest
that IAD offers significant quality-of-life benefits,
particularly with regard to sexual function during the offtreatment phase. IAD represents significant savings, in terms
both of reduced medication needs and of reduced costs for
managing the complications of prolonged CAS.