EBM 泌尿科 VS林漢青

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

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

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

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

The "5S" levels of organisation of evidence from healthcare research Brian Haynes, R Evid Based Med 2006;11:162-164 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.

Key word for search Hypogonadism Prostate cancer Testosterone therapy

Summaries

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)

Synopses

Syntheses

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)

Studies

Origin: International Journal of Impotence Research 2009

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

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

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

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

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

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

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