# The relationship between testosterone replacement therapy and incidence of proximal humerus fractures in men: a matched retrospective analysis

## TL;DR

This study finds that testosterone replacement therapy is linked to a higher risk of proximal humerus fractures in men, suggesting a need for careful patient management.

## Contribution

The study provides new evidence linking testosterone replacement therapy to increased proximal humerus fracture risk using a large matched-cohort analysis.

## Key findings

- TRT patients had a higher incidence of proximal humerus fractures (0.029%) compared to controls (0.005%).
- Logistic regression showed TRT was associated with a 3.14-fold increased risk of PHF.

## Abstract

Anabolic androgenic steroid supraphysiologic dose use is linked to an increased risk of tendon rupture. Testosterone replacement therapy (TRT) is used to treat hypogonadism and is associated with increased bone mineral density. However, its relationship with fracture risk, particularly proximal humerus fractures (PHF), remains uncertain. This study evaluates the association between TRT and the incidence of PHFs using a large national database. We hypothesized that TRT use would be associated with a difference in the incidence of PHFs compared to a control group due to testosterone's role in maintaining bone mineral density.

This retrospective study with one-to-one matching queried the PearlDiver Mariner165 dataset to obtain a random sample of 500,000 patients aged 35 to 75 who received TRT continuously for at least 3 months and a random control sample of 500,000 different patients. Of the targeted 1,000,000 patients, 335,753 pairs of patients were matched based on age, tobacco use, diabetes history, and the Charlson Comorbidity Index. Incidence of PHF was assessed over a 2-year follow-up using the International Classification of Diseases codes, with comparisons made across the different cohorts. Multivariable logistic regression was conducted to identify the association between TRT use with PHF in men. An alpha level of 0.01 was prespecified to reduce the risk of type I error and ensure statistical rigor.

In this matched-cohort study of 335,753 paired TRT and control patients, the mean age was 53.82 ± 10.58 years. Patients administered TRT demonstrated a higher incidence of PHF compared to the control cohort (0.029% vs. 0.005%, P < .001). Logistic regression analysis demonstrated that TRT was associated with a significantly increased risk of PHF (adjusted odds ratio 3.14; 95% confidence interval: 1.84-5.59; P < .001).

In this retrospective matched-cohort study, TRT patients demonstrated an increase in 2-year incidence rates of PHF in men. These findings underscore the need for tailored patient management and provide actionable insights for orthopedic practice. Future studies of prospective design are needed to better address confounding factors, establish causation, and evaluate surgical outcomes in TRT patients.