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Yarnell CJ, Thiruchelvam D, Redelmeier DA Risks of Serious Injury with Testosterone Treatment. Am J Med. 2021 Jan;134(1):84-94.e6. doi: 10.1016/j.amjmed.2020.07.037. Epub 2020 Sep 12. (Original study)
Abstract

BACKGROUND: Injury causes significant morbidity and mortality that is sometimes attributed to testosterone and violence. We hypothesized that prescribed testosterone might be associated with the subsequent risk of serious injury.

METHODS: We conducted a self-matched individual-patient exposure-crossover analysis comparing injury risks before and after initiation of testosterone. We selected adults treated with testosterone in Ontario, Canada, from October 1, 2012, to October 1, 2017 (enrollment) and continued until October 1, 2018 (follow-up). The primary outcome was defined as an acute traumatic event that required emergency medical care.

RESULTS: A total of 64,386 patients were treated with testosterone of whom 89% were men with a median age of 52 years. We identified 34,439 serious injuries during the baseline interval before starting testosterone (584 per month) and 7349 serious injuries during the subsequent interval after starting testosterone (565 per month). Rates of injuries were substantially above the population norm in both intervals with no significant increased risk after starting testosterone (relative risk?=?1.00; 95% confidence interval: 0.96-1.04, P?=?0.850). The unchanged risk extended to diverse patients, was observed for different formulations and applied to all injury mechanisms. In contrast, testosterone treatment was associated with a 48% increased risk of a thromboembolic event (relative risk?=?1.48; 95% confidence interval: 1.25-1.74, P < 0.001).

CONCLUSIONS: Testosterone treatment was associated with a substantial baseline risk of serious injury that did not increase further after starting therapy. Physicians prescribing testosterone could consider basic safety reminders to mitigate injury risks.

Ratings
Discipline Area Score
Family Medicine (FM)/General Practice (GP) 5 / 7
General Internal Medicine-Primary Care(US) 5 / 7
Endocrine 5 / 7
Internal Medicine 5 / 7
Comments from MORE raters

Endocrine rater

This is an interesting study with good methods and wide generalizability. The findings are reassuring, but they were unable to capture other violence-related outcomes (e.g. law enforcement trouble, injuries to others).

Family Medicine (FM)/General Practice (GP) rater

This research doesn't really answer the question of whether there is a link between testosterone and violence, due to its study design type and short duration. It raises more questions however, as to why individuals with low testosterone may have more presentations for serious injuries.

Family Medicine (FM)/General Practice (GP) rater

This is a really interesting study. Testosterone prescribing is increasing. The most significant finding is that the population of people coming for testosterone therapy are substantially more at risk of serious injury than the general population, but that this risk in not further increased by being prescribed testosterone. The thromboembolic risks of testosterone therapy are already known but are emphasised.

Family Medicine (FM)/General Practice (GP) rater

Clever study. It's interesting that this is such a high risk population.

General Internal Medicine-Primary Care(US) rater

This study has multiple design flaws making interpretation difficult. Other studies have already demonstrated that testosterone is associated with increased risk of thrombotic disease, CV disease, and prostate cancer and should not be prescribed unless there are clear benefits that outweigh these risks.

General Internal Medicine-Primary Care(US) rater

As an internist, I find the main result initially appeared unexpected but when I consider the patients who may go to clinics such as those in the U.S. that advertise on TV promising to "increase virility" and help men "please the ladies" if they just come on in for a prescription, I suspect an underlying high injury rate may be present. I, and many colleagues, are well aware of the multiple risks of exogenous testosterone and the vast inappropriate prescribing of this drug. The authors note the limitations of the study, and did not have a way to determine the amount of injury to people other than the patient, which would have been helpful.
Comments from EvidenceAlerts subscribers

Dr. Tony Glaser (12/5/2020 11:23 AM)

Does not really seem to amount to much at all. People (including women, it seems) who are about to be prescribed testosterone have higher than normal risk for injury, and when they use testosterone, they continue to have higher than normal (but perhaps slightly reduced) risk. My guess would be that people seeking testosterone are more physically active (going to gyms, playing sports, running, and who knows what else) than people not seeking testosterone (after all, they may be more concerned about real or imagined physical declines with age) and so are more likely to have injuries. Now, if the data showed that men taking testosterone were more likely to be injured in bar fights than similar men not taking testosterone, that would be interesting . . . but this is far from that kind of data