Deaths and Cardiovascular Events in Men Receiving Testosterone Sandeep Dhindsa, MBBS1; Manav Batra, MBBS2; Paresh Dandona, MBBS2

JAMA. 2014;311(9):964. doi:10.1001/jama.2014.389.

[+]Author Affiliations

To the Editor The retrospective study by Dr Vigen and colleagues 1 on the association of testosterone therapy with adverse outcomes was limited by the short duration of therapy and the modest increase in testosterone concentrations following treatment.

The duration of treatment on average was approximately 1 year. In clinical terms, this would probably be considered short-term therapy. Also, 40% of patients did not have a testosterone concentration checked after the initiation of testosterone therapy. Of the 60% who had it checked, the testosterone concentration increased from a baseline of 175.5 ng/dL to 332.2 ng/dL for the first repeat testosterone measurement. Because testosterone therapy is generally titrated to raise testosterone level to approximately 500 ng/dL, 2 the study population may have been undertreated. Can the authors clarify if the patients had any further increase in testosterone concentration at subsequent measurements?

The 17.6% of patients prescribed testosterone therapy who filled only 1 prescription should probably have been excluded from the testosterone therapy group. It is also not clear if 1 prescription meant 30 days or 90 days of treatment.

The increased risk of adverse outcomes associated with testosterone therapy may simply be reflective of the baseline differences between the 2 groups. Patients in the testosterone therapy group had lower baseline testosterone concentrations (175.5 ng/dL vs 206.5 ng/dL in the untreated group). Because endogenous testosterone concentrations are inversely related to mortality in elderly men, 3 data should be analyzed after adjustment for baseline testosterone concentrations.

A previous study 4 that showed an increase in cardiovascular events after short-term testosterone therapy in elderly men with multiple comorbidities found an association of event rate with a large increase in testosterone concentrations. Can the authors provide the change in testosterone concentrations after testosterone therapy in men who had an event vs those who did not?

A recent retrospective chart analysis 5 demonstrated that testosterone therapy in men with type 2 diabetes reduces mortality by 56%. Did the authors perform a subgroup analysis of the association in patients with diabetes? Half of the patients in the study had diabetes. Level of hemoglobin A1c also should have been included in the multivariable adjustment.

Article Information Corresponding Author: Sandeep Dhindsa, MBBS, Texas Tech University Health Sciences Center, 701 W Fifth St, Odessa, TX 79763 (

Conflict of Interest Disclosures: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Dhindsa reported receiving speaker’s honoraria from AbbVie and consulting honoraria from Janssen. No other disclosures were reported.

Section Editor: Jody W. Zylke, MD, Senior Editor.

References 1 ↵ Vigen R, O’Donnell CI, Barón AE, et al. Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels. JAMA. 2013;310(17):1829-1836.PubMed

2 ↵ Bhasin S, Cunningham GR, Hayes FJ, et al; Endocrine Society Task Force. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2010;95(6):2536-2559.PubMed

3 ↵ Laughlin GA, Barrett-Connor E, Bergstrom J. Low serum testosterone and mortality in older men. J Clin Endocrinol Metab. 2008;93(1):68-75.PubMed

4 ↵ Basaria S, Davda MN, Travison TG, Ulloor J, Singh R, Bhasin S. Risk factors associated with cardiovascular events during testosterone administration in older men with mobility limitation. J Gerontol A Biol Sci Med Sci. 2013;68(2):153-160.PubMed

5 ↵ Muraleedharan V, Marsh H, Kapoor D, Channer KS, Jones TH. Testosterone deficiency is associated with increased risk of mortality and testosterone replacement improves survival in men with type 2 diabetes. Eur J Endocrinol. 2013;169(6):725-733.PubMed

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