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1	Androgens, Benign Prostactic Hyperplasia, and Prostate Cancer – Is There a Connection? Richard F. Spark, MD, FACE Beth Israel Deaconess Medical Center Harvard Medical School Boston, Massachusetts
2	Words from a Nobel Laureate “Orchiectomy or the administration of phenolic estrogens resulted in regression of cancer of the human prostate, whereas in untreated cases testosterone enhanced the growth of the neoplasm” Dr. Charles Huggins – December 13, 1966
3	Testosterone and the Prostate A. 1940-Huggins Androgen Deprivation BPH and Prostate Ca a. Surgery b. E2 c. GnRH agonists/antagonists d. Herbs-PC-SPES B. “Androgen Independent” Prostate Ca
4	Prostate Cancer- Estimate of the Disease-free Interval
5	Prostate Cancer-Overall Survival
6	2003-Clinical Conundrum
7	Given Induced T. deficiency prolongs survival in prostate cancer In T. deficient men Does T Rx. increase BPH risk? Does T Rx.increase prostate Ca risk? Is prostate biopsy mandatory?
8	In Testosterone Deficient Men
9	Hypogonadism-Central Prostate Volume With and Without T vs. Age-Matched Controls
10	Hypogonadal Men vs. Age-Matched Controls
11	Parenteral or Topical Testosterone in Men > 70 Years
12	Anabolic Androgen Abuse
13	Prostate Cancer-2003 Diagnoses: 189,000 Deaths: 30,200 Lifetime risk Diagnosis 1 in 6/Death 1 in 29 Median age: Diagnosis 71/Death 78 Black men prevalence > 60% higher
14	Androgens and Prostate Cancer
15	Hormones and Prostate Ca from Schatzl Prostate 2000;44:219-224
16	Occult Prostate Cancer in Men With Low Serum Testosterone Levels
17	Prostate Ca and Hypogonadism?
18	PSA Men > 65 Years of Age Testosterone vs. Placebo
19	Testosterone vs.Placebo X 3 Years N=108
20	Animal Prostate Models “All mammals have prostates but only man, dog and the African lion develop prostate disease” That was before science gave us the Noble rat Norway Brown rat ArKO mouse
21	The Noble (NBL) Rat T + E2 causes 100% dorsolateral prostate (DLP) dysplasia and high prolactin (Prl) Bromocriptine diminishes dysplasia The antiestrogen ICI 182,780 prevents DLP dysplasia ICI 182,780 reverses protooncogenes activated by T+E2
22	Androgen Receptor (AR) in The Brown Norway Rat T/E2 ratio declines with age Prostatic dysplasia in DLP and LP but not VP AR decrease in VP but 2.7 and 1.3 x increase in DLP and LP Castration transient (7-10 d) AR decline Age-dependent AR is the culprit
23	BPH but no Ca in Aromatase KO (ArKO) Mice Aromatase encoded by cyp19 gene in ArKO mice T, DHT, Prl increase Hyperplasia in VP, DLP, AP lobes Despite chronic (56 wk) serum and tissue T, DHT, Prl increases prostate malignancy does not occur in the absence of E2
24	Androgens and the Prostate Conclusions In hypogonadal men androgen supplements: Increase CPV May increase PSA Can be used safely Do not appear to increase BPH or prostate Ca risk above age-matched men with normal testosterone.