Prostate Safety Events During Testosterone Replacement Therapy in Men With Hypogonadism

Key Points Question Does testosterone replacement therapy in men with hypogonadism increase the risk of high-grade or any prostate cancer or other adverse prostate events? Findings During 14 304 person-years of follow-up of 5204 men (aged 45-80 years) with hypogonadism in this randomized clinical trial, incidences of high-grade or any prostate cancer, acute urinary retention, invasive surgical procedures, and new pharmacologic treatment were low and did not differ significantly between groups. Meaning The study’s findings will facilitate a more informed appraisal of the potential prostate risks of testosterone replacement therapy.


eAppendix 2. The TRAVERSE Prostate Study Committee
The Prostate Subcommittee of the TRAVERSE Study crafted the Prostate Safety Monitoring Plan and the Statistical Analyses Plan for the analyses of the prostate safety endpoints; performed the analyses of the prostate safety data, and was led by Shalender Bhasin, MB, BS, at the Harvard Medical School, Brigham and Women's Hospital in Boston, MA.The Subcommittee's members included Shalender Bhasin, MB, BS (Chair), Harvard Medical School, Brigham and Women's Hospital, Boston, MA; Ian

Funding
The trial was funded by a consortium of testosterone manufacturers led by AbbVie, Inc. (North Chicago, IL) with additional financial support provided by Endo Pharmaceuticals (Malvern, PA), Acerus Pharmaceuticals Corporation (Ontario, Canada), Upsher-Smith Laboratories, LLC (Maple Grove, MN).Dr. Bhasin was supported in part by Thje Boston Claude D. Pepper Older Americans Independence Center grant 3P3031679 from the National Institute on Aging.Legend: For each analyte, baseline counts and means (SDs) of subjects with at least one follow-up value are shown.

Prostate Adjudication Committee
At each post-baseline timepoint, counts and at-visit means (SDs) of subjects with data at both baseline and indicated timepoint are shown.Change from baseline for each treatment group and the difference between treatment groups (TRT minus placebo) are given as LS means with 95% confidence intervals.
To convert dihydrotestosterone (ng/dL) to SI units (nmol/L), multiply the DHT concentration by 0.0344.
Serum total testosterone and estradiol levels have been reported previously (Lincoff 2023).
Thompson, MD, CHRISTUS Santa Rosa Health System and The University of Texas Health Science Center, San Antonio, TX; Thomas G. Travison, PhD, Marcus Institute for Aging Research, Hebrew Senior Life; Division of Gerontology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA; Karol M. Pencina, PhD, Harvard Medical School, Brigham and Women's Hospital in Boston, Sandra Fukumoto, MBA; Michael C. Snabes, MD, PhD; Anna Chan, PharmD; Elena Dubcenco, MD, MS; Xue Li, PhD; Rachel A. Preuss, MS; Samantha J. Phillips, MPE, PMP; Thomas J. Korellis, BS.
Darren K. McGuire, MD MHSc, University of Texas Southwestern Medical Center, Dallas, TX; Janet Wittes, PhD, Wittes LLC, Washington, D.C.; Renato D. Lopes, MD, PhD (Observer, non-voting), Duke Clinical Research Institute, Durham, NC; Andrew Armstrong, MD, ScM (ad hoc consult), Duke University Medical Center, Duke Cancer Institute Center for Prostate and Urologic Cancers, Durham, NC eFigure 1. Sensitivity Analysis of the Primary and Major Secondary Prostate Safety Endpoints Using a Cox Proportional Hazards Model eFigure 2. Sensitivity Analysis of the Primary and Major Secondary Prostate Safety Endpoints Using the Same Discrete Proportional Hazards Model as the Primary Analysis but Censoring Events Occurring After One Year Following End of Treatment eFigure 3. Sensitivity Analysis of the Primary and Major Secondary Prostate Safety Endpoints Using the Same Discrete Proportional Hazards Model as the Primary Analysis but Censoring Events Occurring After 30 Days Following End of Treatment eFigure 4. Changes in PSA Levels From Baseline in the TRT and Placebo Groups Symbols represent the LS mean estimates of the change from baseline, and whiskers represent the associated 95% confidence interval.eTable 1. Maximum Attained PSA Values in ng/mL Prior to Prostate Biopsy for Men Diagnosed With Prostate Cancer Michael O'Leary, MD, PAC Chair; Scott Lucia, MD, Mark A. Preston, MD; A. John Kellog Parsons, MD, MHS 5. Data Monitoring Committee John H. Alexander, MD, MHSc (Chairman), Duke Clinical Research Institute, Duke University, Durham, NC; William Bremner, MD, PhD, University of Washington, Seattle, WA; Eric Klein, MD, Cleveland Clinic, Cleveland, OH;