Mortality Among Users of Anabolic Steroids

Androgenic anabolic steroids (AAS) are highly effective in promoting muscle growth.^1,2 In 2014, it was estimated that about 3 million to 4 million individuals in the US had used AAS in their lifetime.¹ Unfortunately, these drugs are associated with a range of serious adverse effects including severe cardiovascular and psychiatric morbidity and death.^2,3 However, data are limited to case reports and smaller cohorts.² We investigated mortality and cause of death among a large cohort of AAS users, with a comprehensive follow-up period, and compared the cohort with a control group.

We included Danish males who received a doping sanction of 2 years of sports exclusion as part of an AAS antidoping program, identified through sporadic inspections and drug testing in fitness centers in Denmark from January 3, 2006, to March 1, 2018.³ These centers were accessible to the public and members were informed about the possibility of unannounced doping controls. The cohort encompassed both casual and dedicated gym visitors. For each AAS user, 50 male control participants from the general population were randomly included through the Danish Civil Registration System.⁴ Control participants were matched by age and enrollment day. Follow-up continued until death, migration, or June 30, 2023.

Every resident in Denmark is assigned a personal identification number used for interactions with the health care system.⁴ We cross-referenced the personal identification numbers of study participants with the Danish Civil Registration System to obtain records on their living status and, for those deceased, their exact dates of death. Additionally, we identified the primary causes of death, as determined by physicians, from the National Causes of Death Register.⁴ These were categorized into natural or unnatural causes (accidents, violent crimes, or suicide). To ensure anonymity, a complete list of death causes was not permitted.

All-cause mortality was investigated with the Kaplan-Meier estimator, and statistical significance was assessed with the log-rank test. Hazard ratios (HRs) were estimated with Cox proportional hazard regression models. Causes of death were analyzed with a competing risk model, incorporating unknown death causes through imputation based on complete cases (Supplement 1). Statistical significance was determined at a 2-sided P < .05. HRs were presented with 95% CIs. All statistics were computed in SAS version 9.4 (SAS Institute Inc).

This register-based study, not requiring informed consent according to Danish law, received approval from the Danish National Board of Health and the Danish Data Protection Agency.

This study included 1189 males sanctioned for doping with AAS and 59 450 male control participants. The mean age among AAS users and control participants was 27.4 (SD, 6.9) years.

The cohort had a mean follow-up time of 11 years (Table). In the control cohort 5.47% were right censored due to migration, compared with 2.10% for AAS users.

During follow-up 33 AAS users died, compared with 578 in the control group, resulting in an HR of 2.81 (95% CI, 1.98-3.99; P < .001) (Table and Figure). Among AAS users, there were 17 deaths categorized as unnatural, primarily from accidents, and 16 deaths classified as natural causes, with the most prevalent causes being cancer and cardiovascular disease. Among the control participants, there were 334 natural deaths—208 unnatural, and 36 with unknown causes. The HR for an unnatural death among AAS users compared with control participants was 3.64 (95% CI, 2.22-5.96; P < .001); for natural death, the HR was 2.24 (95% CI, 1.36-3.70; P = .002).

This study found an increase in mortality from both natural and unnatural causes among AAS users sanctioned in fitness centers compared with control participants. The increased risk of death among AAS users aligns with results from smaller cohort studies.²

Study limitations include its observational nature, which does not establish causality, and an absence of adjustment for potential confounding variables affecting health. In Denmark, AAS use is considered outside social norms.^3,5 Behaviors possibly associated with AAS use, such as risk-taking propensities or the use of other substances, may contribute to the elevated mortality risks observed.^1,5

Accepted for Publication: February 21, 2024.

Published Online: March 14, 2024. doi:10.1001/jama.2024.3180

Corresponding Author: Josefine Windfeld-Mathiasen, MD, Department of Clinical Pharmacology, Bispebjerg and Frederiksberg Hospital, Bispebjerg Bakke 23, 2400 Copenhagen NV, Denmark (josefine.windfeld-mathiasen@regionh.dk).

Author Contributions: Dr Horwitz had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Windfeld-Mathiasen, Heerfordt, Andersen, Horwitz.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: All authors.

Critical review of the manuscript for important intellectual content: All authors.

Statistical analysis: Andersen, Horwitz.

Obtained funding: Windfeld-Mathiasen, Dalhoff, Horwitz.

Administrative, technical, or material support: Windfeld-Mathiasen, Heerfordt, Horwitz.

Supervision: Heerfordt, Dalhoff, Andersen, Horwitz.

Conflict of Interest Disclosures: Dr Dalhoff reported serving as a board member for Anti Doping Danmark from 2015 to 2020. No other disclosures were reported.

Funding/Support: This work was supported by a research grant from Anti Doping Danmark (Dr Windfeld-Mathiasen, Dr Horwitz).

Role of the Funder/Sponsor: Anti Doping Danmark had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Data Sharing Statement: See Supplement 2.