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Am Fam Physician. 2013;88(8):online

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Clinical Question

In patients who are presumed cured of organ-confined prostate cancer, what are the benefits of testosterone replacement therapy, and what is the risk of cancer recurrence?

Evidence-Based Answer

Men with symptomatic androgen deprivation who have had clinically curative treatment for organ-confined prostate cancer may have symptomatic improvement with testosterone replacement therapy. (Strength of Recommendation [SOR]: C, based on two small case series.) There are no studies evaluating the risk of cancer recurrence in patients receiving testosterone replacement therapy. However, testosterone replacement therapy may be associated with increased prostate-specific antigen (PSA) levels. (SOR: C, based on one case report.) Some men discontinue therapy because their symptoms do not improve. (SOR: C, based on a small case series.)

Evidence Summary

Seven case series (n = 206 patients) describe symptomatic improvements in men with androgen deprivation syndrome who received testosterone replacement therapy.17 PSA levels were monitored over periods ranging from six months to 12 years. All of the case series included men who received clinically curative therapy for organ-confined prostate cancer; five used radical prostatectomy,15 one used brachytherapy,6 and one used external beam radiotherapy7 (Table 114,6,7 ).

Case seriesDefinitive therapyBaseline Gleason scoreMean/median follow-up (range)Normal serum testosterone level achieved?OutcomesRecurrence (based on PSA level)
Kaufman (2004)1 n = 7; mean age = 64 yearsRadical prostatectomy61018 months (6 months to 12 years)Yes: 6 Unknown: 13 participants reported symptom improvementNone
Agarwal (2005)2 n = 10; mean age = 54 yearsRetroperitoneal radical prostatectomy27119 months (NA)Yes: 10Decreased hot flashes, increased energyNone
Nabulsi (2008)3 n = 22; mean age = 61 yearsRadical prostatectomy137224 months (14 to 30 months)Yes: 22Not reported1 (Gleason score = 8)
Khera (2009)4 n = 57; mean age = 64 yearsRadical prostatectomy2426413 months (7 to 17 months)Yes: 57Not reportedNone
Sarosdy (2007)6 n = 36; mean age = 65 yearsBrachytherapy (with or without external beam radiotherapy)22634.5 years (1.5 to 9 years)Yes: 315 participants discontinued therapy because of no perceived benefitNone
Morales (2009)7 n = 5; mean age = 66 yearsExternal beam radiotherapy21215 months (6 to 27 months)Unknown: 54 participants reported decreased hot flashes, improved libido, and increased energyFinal PSA level < 1.5 ng per mL (1.5 μg per L)
2 participants had improved erectile function

Two case series evaluated androgen deprivation symptoms in patients receiving testosterone replacement therapy.2,7 The first study included 10 men (average age = 54 years) who used the hormonal assessment subscale of the Expanded Prostate Cancer Index Composite.2 This self-administered quality-of-life questionnaire measures hot flashes, breast tenderness, depression, low energy, and weight change. On a scale of 0 (no improvement) to 100 (maximum improvement), scores for patients receiving testosterone replacement therapy improved from 38 (95% confidence interval [CI], 32 to 46) to 49 (95% CI, 46 to 54). The second study described five men (average age = 66 years) who had 30 androgen-related symptoms (e.g., hot flashes, decreased libido, erectile dysfunction, lack of ejaculation, fatigue, muscle aches, depressed mood).7 After testosterone replacement therapy, the men had only 14 symptoms.

No studies have evaluated the risk of cancer recurrence after testosterone replacement therapy. The seven case series discussed above monitored PSA levels and found one patient with an unexpected increase.17 The authors did not describe a clinical recurrence of cancer in that case. In one case series, five of 36 patients discontinued therapy because of a lack of perceived symptomatic benefit, and one patient reported headache.6

Recommendations from Others

A 2008 consensus guideline from the International Society of Andrology, International Society for the Study of the Aging Male, European Association of Urology, European Academy of Andrology, and American Society of Andrology states that men successfully treated for prostate cancer who have confirmed symptomatic hypogonadism are candidates for testosterone replacement therapy if there is no clinical or laboratory evidence of residual cancer. It states that physicians should discuss the risks and benefits of therapy with the patient and ensure close follow-up.8 The Endocrine Society recommends against initiating testosterone replacement therapy in this population.9

Clinical Inquiries provides answers to questions submitted by practicing family physicians to the Family Physicians Inquiries Network (FPIN). Members of the network select questions based on their relevance to family medicine. Answers are drawn from an approved set of evidence-based resources and undergo peer review. The strength of recommendations and the level of evidence for individual studies are rated using criteria developed by the Evidence-Based Medicine Working Group (

The complete database of evidence-based questions and answers is copyrighted by FPIN. If interested in submitting questions or writing answers for this series, go to or email:

This series is coordinated by John E. Delzell Jr., MD, MSPH, associate medical editor.

A collection of FPIN’s Clinical Inquiries published in AFP is available at

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