The Formulary Files

Conflicting data on testosterone replacement therapy

Krishna Rutvij Patel, Pharm D

Trimel’s Natesto, a nasal treatment indicated as testosterone replacement therapy (TRT), is entering the market at a time when many are questioning the safety of TRTs.

On May 28, Natesto joined Fortesta, Testim, AndroGel, Axiron, Androderm, and Striant as noninvasive formulations for hypogonadism. Although the hypogonadism market has been expanding in recent years, emerging evidence questions TRT’s long-term safety, as there is mixed data suggesting increased risk of cardiovascular (CV) events and prostate cancer.

Two recently published studies by Vigen, et al., and Finkle, et al., suggest that TRT leads to increased risk of cardiovascular events. Yet another recently published study, by Tan, et al., suggests that TRT may actually have a protective effect when it comes to CV disease.

Furthermore, a recent study published by Cui, et al., suggests that TRT may not lead to increased risk of prostate cancer.

Why all of this contradiction? Aren’t studies supposed to objectively provide an answer that formulary decision makers can use? The studies providing conflicting conclusions regarding risk of CV events are observational studies, not large-scale long-term randomized control trials.

Finkle, et al.’s study regarding risk of prostate cancer is a meta-analysis of randomized controlled trials, although a single large-scale randomized controlled trial is needed to resolve the conflicts in data for risk of prostate cancer as well.


  1. Vigen R, O’Donnell C, Baron AE, et al. Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels. JAMA. 2013;310:1829–1836.
  2. Finkle WD, Greenland S, Ridgeway GK, et al. Increased risk of non-fatal myocardial infarction following testosterone therapy prescription in men. PLoS One. 2014;9:e85805.
  3. Tan R, Cook KR, Reilly WG. Testosterone therapy is not associated with higher risk of myocardial infarction or stroke: the low T experience [abstract]. AACE. 2014: 1353.
  4. Cui Y, Zong H, Yan H, Zhang Y. The effect of testosterone replacement therapy on prostate cancer: a systematic review and meta-analysis. Prostate Cancer Prostatic Dis. 2014;17:132–143.


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