Letter to the Editor regarding ‘Treatment of Men for “Low Testosterone”: A Systematic Review’ by Huo et al.; Testosterone Replacement Therapy: Toward to the Robust Evidence and Facts

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Letter to the Editor

Received: Oct 28, 2016; Revised: Nov 11. 2016; Accepted: Nov 18, 2016 Correspondence to: Sang-Kuk Yang

Department of Urology, Konkuk University School of Medicine, 82 Gugwon-daero, Chungju 27376, Korea.

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Letter to the Editor regarding ‘Treatment of Men for “Low

Testosterone”: A Systematic Review’ by Huo et al.; Testosterone Replacement Therapy: Toward to the Robust Evidence and Facts

Jae Hung Jung^1,2,3, Sang-Kuk Yang⁴

1Department of Urology, ²Institute of Evidence Based Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea, ³Cochrane Urology Review Group, Minneapolis Veterans Healthcare System, University of Minnesota, Minneapolis, MN, USA, ⁴Department of Urology, Konkuk University School of Medicine, Chungju, Korea

　We read with interest the systematic review (SR) by Huo et al [1] on the role of testosterone replacement therapy (TRT) for treating men with low testosterone, which sug- gests that there is no beneficial effect in most men. While we cannot rule out that the author’s conclusions will ulti- mately be proven to be true, we believe that it is premature to make this determination based on the current study.

　SRs play a critical role in guiding evidence-based clinical practice but to do so, they need to include a compre- hensive search of the published and unpublished literature as well as rating of the quality of evidence [2]. The search of this SR was outdated (November 2013) by the time of publication (September 2016) and lacks a dedi- cated effort to search the so-called grey literature to avoid publication bias. Furthermore, the Jadad system for assessing risk of bias, despite an appealing simplicity, falls short of current methodological expectations and is no longer recommended [3]. Instead, the Cochrane risk of bias tool has become the widely excepted “gold standard” for assessing the risk of bias of randomized controlled trials [2].

Even more importantly, the study lacks a formal quality of evidence rating. This should be conducted on a per out- come basis and consider additional domains aside from

study limitation such as indirectness, imprecision, incon- sistency and publication bias. Another important issue is that of clinical heterogeneity. Studies included in this SR demonstrated a wide range of ages and medical comorbi- dities and encompassed a variety of questionnaires to evaluate sexual function, preparations of testosterone, and durations of follow-up period. These differences are likely important and deserve more attention that the current SR provides.

　We are well aware of TRT remains somewhat con- troversial, over the risks and benefits. In 2015, the US Food and Drug Administration released recommending that all prescription testosterone products are approved only for men who have low testosterone levels caused by certain medical conditions due to possible increased risk of adverse cardiovascular effect [4]. However, they also agree that the signal of cardiovascular risk is weak and that only a prospective, well-controlled clinical trial could de- termine whether testosterone causes cardiovascular adverse events due to methodological limitations [4].

　As a result, we should seek to provide the explicit sys- tematically developed answers for hypogonadal men with erectile dysfunction using methodologically rigorous and

pISSN: 2287-4208 / eISSN: 2287-4690

World J Mens Health 2016 December 34(3): 224-225 https://doi.org/10.5534/wjmh.2016.34.3.224

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Jae Hung Jung and Sang-Kuk Yang: Testosterone Replacement Therapy Ttoward To The Evidence 225

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transparent standards like those adopted by Cochrane Collaboration, while at the same time assessing the bal- ance between desirable and undesirable effects, the pa- tient’s presumed values and preferences, and the potential economic impact of testosterone supplementation.

CONFLICT OF INTEREST

　No potential conflict of interest relevant to this article was reported.

REFERENCES

1. Huo S, Scialli AR, McGarvey S, Hill E, Tügertimur B,

Hogenmiller A, et al. Treatment of men for “low testosterone”:

a systematic review. PLoS One 2016;11:e0162480.

2. Tseng TY, Dahm P, Poolman RW, Preminger GM, Canales BJ, Montori VM. How to use a systematic literature review and meta-analysis. J Urol 2008;180:1249-56.

3. Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 1996;17:1-12.

4. Food and Drug Administration. Summary minutes of the joint meeting of the Bone, Reproductive and Urologic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee Meeting. [cited 2016 May 4]. Available from: http://www.fda.gov/downloads/AdvisoryCommittees/

CommitteesMeetingMaterials/Drugs/ReproductiveHealthDru gsAdvisoryCommittee/UCM418144.pdf.