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1. Hormonal Therapy for
Prostate Cancer

2. • Prostatic epithelium  undergoes atrophy
after castration
• Huggin’s hypothesis  Benign prostatic
epithelium and prostate ca  were
biochemically analogous and they would
respond in a similar fashion to androgen
ablation.

3. Androgen Deprivation Therapy (ADT)
• All current forms of
androgen deprivation
therapy (ADT)  Reducing
the ability of androgen to
activate the ARthrough
lowering levels of androgen
or by blocking AR binding.

4. MECHANISMS OF ANDROGEN
AXIS BLOCKADE
Approaches for androgen axis:
(1) Ablation of androgen sources,
(2) Inhibiting androgen synthesis,
(3) Antiandrogens
(4) Inhibition of LH-RH and/or LH release

7. Ablation of Androgen Sources
• Surgical castration: Bilateral orchiectomy
reduces circulating testosterone levels to < 50
ng/dL In 24 hours testosterone reduced by
>90%

8. • Antiandrogen
• Direct AR blocking effects
• By blocking the testosterone feedback
centrally the nonsteroidal antiandrogens
cause LH and testosterone levels to
increaseThis allows antiandrogen activity
without inducing hypogonadism
• Bicalutamide monotherapy appears to have
equivalent efficacy to surgical castration

9. Inhibition of LH-RH
LH-RH Agonists
• The LH-RH agonists exploit the desensitization of LH-
RH receptorsin the anterior pituitary after chronic
exposure to LH-RH, thereby shutting down the
production of LH and testosterone.
• The initial exposure to more potent agonists of LH-RH
results in a flare of LH and testosterone levelsThe
coadministration of an antiandrogen functionally
blocks the increased levels of testosterone.
• Survival after therapy with an LH-RH agonist was
equivalent to that of orchiectomy

11. Inhibition of Androgen Synthesis
• Ketoconazole interferes with two
cytochrome P450–dependent pathways
conversion lanosterol to cholesterol is
blocked Demonstrated loss of adrenal
steroid synthesis and testosterone synthesis
• The effects testosterone levels dropping to
the castrate level within 4 hours of
administration

12. General Complication of Androgen
Ablation
• Osteoporosis
• Hot Flashes
• Sexual Dysfunction
• Declines of Cognitive Function
• Increase of fat body mass and loss of muscle mass
• Increase of Diabetes and metabolic syndrome risks
• Cardiovascular morbidity and mortality
• Gynecomastia and mastodynia
• Anemia

13. PSA and Posititivity of Bone Scan
• The bone scan positivity rate was 2.3%, 5.3%,
16.2%, 39.2% and 73.4% for PSA levels of 0-
9.9, 10-19.9, 20-49.9, 50-99.9 and >
100ng/mL, respectively*
*Abuzallouf S, Dayes I, Lukka H. Baseline staging of newly diagnosed prostate cancer: a summary of
the literature. J Urol 2004 Jun;171(6 Pt 1):2122-7. http://www.ncbi.nlm.nih.gov/pubmed/15126770