I have a history of heart disease, is it safe to go on testosterone?

A series of papers published in well-respected journals (ie JAMA, PLOS one) from 2013-2015 showed an association between adverse CV outcomes (e.g. stroke, heart attack) and testosterone therapy (1, 2). Important factors to keep in mind is that these were retrospective chart reviews, therefore low quality evidence and at best should serve as hypothesis generating. In addition, a general principle of medical literature is that associations should never be equated with causation. Around that same time there were other published retrospective and cohort studies showing opposite findings and in fact suggested cardio-protection and improved mortality from testosterone therapy (3, 4). Nevertheless, in 2015 the FDA released a statement: “We are also requiring these manufacturers to add information to the labeling about a possible increased risk of heart attacks and strokes in patients taking testosterone”. Thus the myth was born which still persists to this day. There are no randomized controlled studies in which testosterone is given that shows an increased risk of cardiovascular disease. A new meta-analysis (considered the epitome of evidence based research) published 2022 in the Lancet showed no harm in men using testosterone hopefully putting this issue to rest(5). In fact, having a low testosterone level actually carries an increased risk of cardiovascular disease which is mitigated via exogenous replacement therapy (6).

Often policy statements and guidelines have political/economic motivations behind them, unfortunately for the vast majority delving deep into the scientific literature is simply not feasible. In summary, testosterone optimization therapy does not cause increased cardiovascular risk/mortality and actually improves such outcomes.

 

1. Vigen R, O’Donnell CI, Baron AE, Grunwald GK, Maddox TM, Bradley SM, et al. Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels. JAMA. 2013;310(17):1829-36. Epub 2013/11/07. doi: 10.1001/jama.2013.280386. PubMed PMID: 24193080.
2. Finkle WD, Greenland S, Ridgeway GK, Adams JL, Frasco MA, Cook MB, et al. Increased risk of non-fatal myocardial infarction following testosterone therapy prescription in men. PLoS One. 2014;9(1):e85805. Epub 2014/02/04. doi: 10.1371/journal.pone.0085805. PubMed PMID: 24489673; PubMed Central PMCID: PMC3905977 Section to state that 1) William Finkle is owner of Consolidated Research Inc. (CRI) 2) John Adams, Sander Greenland, Gregory Ridgeway and Melissa Frasco are consultants to CRI. 3) CRI is a company that develops statistical methods and software. 4) None of the authors has been compensated by any manufacturers of products examined in our study. These affiliations do not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials.
3. Baillargeon J, Urban RJ, Kuo YF, Ottenbacher KJ, Raji MA, Du F, et al. Risk of Myocardial Infarction in Older Men Receiving Testosterone Therapy. Ann Pharmacother. 2014;48(9):1138-44. Epub 2014/07/06. doi: 10.1177/1060028014539918. PubMed PMID: 24989174; PubMed Central PMCID: PMC4282628.
4. Shores MM, Smith NL, Forsberg CW, Anawalt BD, Matsumoto AM. Testosterone treatment and mortality in men with low testosterone levels. J Clin Endocrinol Metab. 2012;97(6):2050-8. Epub 2012/04/13. doi: 10.1210/jc.2011-2591. PubMed PMID: 22496507.
5. Hudson J, Cruickshank M, Quinton R, Aucott L, Aceves-Martins M, Gillies K, et al. Adverse cardiovascular events and mortality in men during testosterone treatment: an individual patient and aggregate data meta-analysis. Lancet Healthy Longev. 2022;3(6):e381-e93. Epub 2022/06/18. doi: 10.1016/S2666-7568(22)00096-4. PubMed PMID: 35711614; PubMed Central PMCID: PMC9184259 from AbbVie and National Institutes of Health; consulting fees from Aditum; participation on the Data Safety Monitoring board of OKPO; a leadership or fiduciary role in the Endocrine Society; and a patent (free T calculator based on the ensemble allosteric model, reference 20200174026). SSE reports research grants from AbbVie. MG reports research grants from Otsuka, Bayer, Lilly, Weight Watchers, Novartis, National Health and the Medical Research Council Australia; speaker honoraria from Besins Healthcare, Bayer, and Otsuka; consulting fees from Bayer; and Royalties from Walter and Eliza Hall Institute Melbourne Australia. KLH reports research grants from NIA K23 Career Development Award; a leadership or fiduciary role from Kavod Senior Life Board of Directors, Executive Committee; and stock or stock options from Medaware Systems. NO reports research grants from Dexcom, Roche Diabetes, and Medtronic Diabetes; speaker honoraria from Roche Diabetes; consulting fees from Roche Diabetes and Medtronic Diabetes; payment for expert testimony from London law firm Wilmer Hale; and an issued patent for automatic closed loop glucose control with an adaptive meal bolus calculator. SR reports research grants from North Staffordshire Medical Institute and support for attending meetings or travel from Besins Healthcare. PJS reports research grants from Abbvie and payment for expert testimony from Teva. RQ reports speaker honoraria and support for attending meetings or travel from Bayer. SBhat reports speaker honoraria from Obstetrical & Gynaecological Society of Singapore, Merck SMART Masterclass, and Merck FERRING Forum; leadership or fiduciary role at National Health Service Grampian; editorial role (Editor in Chief of Human Reproduction Open, Special Senior Editor of Cochrane Gynaecology and Fertility); membership of NHS Grampian Board; other financial or non-financial interests from Oxford University Press; and Royalties from Cambridge University Press (Royalties for book Reproductive Medicine for the MRCOG, Cambridge University Press). GBB reports speaker honoraria and consulting fees from Acerus Pharmaceutical. HMT reports consulting fees from Besin Healthcare. EJGil reports provision of study materials from Bayer. All other authors declare no competing interests.
6. Khera M, Miner M, Jaffe J, Pastuszak AW. Testosterone Therapy and Cardiovascular Risk: A Critical Analysis of Studies Reporting Increased Risk. J Sex Med. 2021;18(1):83-98. Epub 2020/12/16. doi: 10.1016/j.jsxm.2020.10.019. PubMed PMID: 33317996.