1. EBM
泌尿科
VS林漢青

2. Background question What is the treatment of hypogonadism?
What is the relationship between testosterone therapy and prostate cancer

3. Huggins & Hodges’ ,1941
Hypogonadal patient received testosterone therapy
Testosterone reduction causes regression of metastatic prostate cancer
Testosterone administration causes prostate cancer growth

4. Foreground question Is that true ?
What ‘s the precise relationship between
endogenous testosterone
exogenous testosterone therapy
prostate cancer

5. PICO P I C O Hypogonadism (without dx of prostate cancer)
Patient/Problem
Hypogonadism
(without dx of prostate cancer) I
Intervention
Testosterone Therapy C
comparison
No testosterone therapy O
Outcome
Prostate cancer or PSA level

6. The "5S" levels of organisation of evidence from healthcare research
Brian Haynes, R Evid Based Med 2006;11:
UpToDate
DynaMed
ACP PIER
BMJ Clinical Evidence
ACP journal club
Evidencebasedmedicine.com
Cochrane Library
BMJ Evidence Updates
Other Systemic reviews eg. PubMed systemic reivew
PubMed
SUMsearch
TRIP
Google
Copyright ©2006 BMJ Publishing Group Ltd.

7. Key word for search
Hypogonadism
Prostate cancer
Testosterone therapy

8. Summaries

9. Conclusion Short-term testosterone therapy
not result in significant adverse effects on prostate tissue in this trial,
Meta-analysis of 19 randomized trials in older men:
Rates of PSA >4 ng/mL and prostate cancer were higher in the testosterone group,
but the rate of prostate biopsy was also higher in the testosterone group, raising the possibility that the higher rate of prostate cancer was due to ascertainment bias. (origin study: not statisically significant)

10. Synopses

11. Syntheses

12. Conclusion JAMA 2006 (RCT,double-blind)
Aging men with late-onset hypogonadism, 6 months of TRT normalizes serum androgen levels but appears to have little effect on prostate tissue androgen levels and cellular functions (6m/o)
Abstract only
Urologii͡a (Moscow, Russia : 1999)
Long-term therapy with testosterone undecanoate has no effect on PSA level(duration:12m/o)

13. Studies

14. Origin: International Journal of Impotence Research 2009

15. Selection of studies for systematic review
Relevant abstract
Full text acquired
Exclusion criteria
A.not monotherapy
B.no hypogonadal
or eugonadal
C.no cancer
D.review article
11/44 studies
Duration: 2m/o ~ 3yrs

16. Conclusion from this systemic review
The prostate cancer incidence was similar
1.3 and 1.5%
Incidence rates for developing prostate cancer  not increase
Endogenous concentrations of serum testosterone have not been directly linked to abnormal changes in PSA

17. Conclusions from above
Testosterone therapy
PSA
Prostate cancer
Androgen (prostate tissue)

18. Critical appraisal Level of evidence Level 與[治療/預防/病因/危害]有關的文獻 1a
Systemic review of RCT 1b
Single RCT 1c
All or none 2a
用多篇世代研究所做成的綜合性分析 2b
單篇cohort及低品質的RCT 2c
Outcome research / ecological studies 3a
SR of case-control studies 3b
Individual case-control studies 4
Case-series(poor quality :cohort / case-control studies) 5
沒有經過完整評讀醫學文獻的專家意見

19. Grades of Recommendation
consistent level 1 studies B
consistent level 2 or 3 studies or extrapolations from level 1 studies C
level 4 studies or extrapolations from level 2 or 3 studies D
level 5 evidence or troublingly inconsistent or inconclusive studies of any level

20. 使用work sheet嚴格評讀
Are the results of this single preventive or therapeutic trial valid?
Was the assignment of patients to treatments randomised?
-and was the randomisation list concealed?
Yes
Were all patients who entered the trial accounted for at its conclusion?
-and were they analysed in the groups to which they were randomised?
yes
Were patients and clinicians kept “blind”
to which treatment was being received?
Only one article JAMA
Aside from the experimental treatment,
were the groups treated equally?
no.
Were the groups similar at the start of the trial?
Participants were similar at baseline with no
significant differences between the groups

21. How long and how many?
“A long-term RCT study would involve following 6000 elderly hypogonadal men for 6 years to determine whether treatment increases the risk of prostate cancer”
The Institute of Medicine Committee on Assessing the Need for Clinical Trials of Testosterone Replacement Therapy in 2004