Survey of the Literature December 2015

Abstract

Comment on: Comparative safety of testosterone dosage forms. JB Layton, CR Meier, JL Sharpless, T Sturmer, SS Jick, MA Brookhart. JAMA Intern Med 2015;175(7):1187–96. Testosterone use continues to increase despite ongoing controversy regarding the potential cardiovascular risks of therapy, which was highlighted in a randomized trial of testosterone gels in older men that demonstrated increased cardiovascular events [1]. This possibility of increased cardiovascular risk with testosterone replacement therapy (TRT) has been a continued debate, where several manuscripts published in high impact factor journals demonstrated increased risk [2,3], and other studies have failed to demonstrate this risk as reality [4,5]. As each delivery mechanism posses varying pharmacokinetics, it is possible that one therapy may potentially carry a higher risk than the others. Injection therapy has been shown to cause a spike in testosterone level after administration, but the use of either a transdermal patch or gel imparts a more subtle increase [6]. In a new-user multicohort comparison study of the use of testosterone injection, gel, and patch, Layton and colleagues found that injection initiators had higher hazards of cardiovascular events when compared with testosterone gel use [7]. These analyses were conducted on three different cohorts of men, including a group of commercially insured men based in the U.S., a Medicare group from the U.S., and a compilation of general practitioner medical records from the U.K.. Patient databases were queried for outcomes to include myocardial infarction (MI), unstable angina, stroke, composite acute events (including MI, unstable angina, or stroke), all-cause hospitalization, mortality, and venous thromboembolism (VTE) that were recorded for up to 1 year after documented initiation of TRT. A total of 544,115 testosterone initiators were analyzed between the 3 cohorts where 55.8% of the patients received gel, 37.4% received injections, and 6.9% were on a patch. As expected, the reported incidence of cardiovascular events over 1 year was low among the younger privately insured US and UK populations when compared with the older aged Medicare sample. Injection initiators had higher hazards of cardiovascular events (ie, MI, unstable angina, and stroke) (1.26; 1.18–1.35), hospitalization (1.16; 1.13–1.19), and death (1.34;1.15–1.56) but not VTE (0.92; 0.76–1.11) when compared with gel initiators. Compared with gels, patches did not confer increased hazards of cardiovascular events (1.10; 0.94–1.29), hospitalization (1.04; 1.00–1.08), death (1.02; 0.77– 1.33), or VTE (1.08; 0.79–1.47). As the authors mentioned, this study is limited based on use of nonrandomized secondary healthcare data. Some of the data sets utilized also lacked to incorporate significant known risk factors of cardiovascular disease. More so, many patients that were included in the study were initiated on TRT without recorded serum testosterone tests or relevant diagnoses, thus, contaminating the population. Despite the possibility that cardiovascular risk may be increased relatively soon after TRT initiation [8], the 1 year follow up analyzed in this study is most likely too short to detect the longterm cardiovascular effects of testosterone via altering lipid levels. Based on the nature of the review, patients receiving in office injection therapy were more likely to be compliant with injections when compared with men who received prescriptions of a patch or gel, as the database © 2015 The Author. Sexual Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Sexual Medicine.

DOI: 10.1002/sm2.88

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@inproceedings{Saitz2015SurveyOT, title={Survey of the Literature December 2015}, author={Theodore Robert Saitz and Johanna L Hannan and Lesley Marson and Michael L. Krychman and Rose Hartzell‐Cushanick and Sophie Bergeron and John D. Dean}, booktitle={Sexual medicine}, year={2015} }