To the Editor:

In their review of testosterone replacement therapy for male hypogonadism,¹ Drs. Heidelbaugh and Belakovskiy noted that testosterone replacement therapy has been shown to increase bone mineral density. However, a recently published secondary analysis of the TRAVERSE trial provides important additional context.² In this large, randomized trial, testosterone therapy was associated with a statistically significant increase in the primary fracture outcome, with similar results in several sensitivity analyses and secondary outcomes. Although the mechanism for this increase is unknown, the effect could be mediated by behavioral changes (eg, increased participation in activities associated with fracture risk) in men randomized to testosterone rather than through a biologic effect on bone tissue.³ However, this analysis provides an important reminder that a positive effect on a disease-oriented outcome (eg, bone mineral density) does not guarantee a favorable effect on the corresponding patient-oriented outcome (eg, fractures). Discussion of possible increased fracture risk should be part of the shared decision-making process with men considering testosterone replacement therapy.

Editor’s Note: This letter was sent to the authors of “Testosterone Replacement Therapy for Male Hypogonadism,” who declined to reply.