Most men with low-grade prostate cancer have an excellent prognosis, with a five-year survival rate of more than 99%. But radical prostatectomy—surgery to remove the prostate—can lead to sexual and physical dysfunction, fatigue, and low mood. A randomized clinical trial led by Shalender Bhasin, MBBS, of the Division of Endocrinology, Diabetes, and Hypertension in the Mass General Brigham Department of Medicine investigated whether testosterone replacement therapy (TRT) could improve these symptoms. Over three months of follow-up, the team found that TRT significantly improved sexual activity, sexual desire, physical function, and aerobic performance compared to placebo. Results are published in JAMA Internal Medicine.
"A history of prostate cancer has been generally viewed as a contraindication for testosterone treatment, but our study found that over three months, TRT was safe and improved sexual and physical function," said corresponding author Bhasin. "While longer and larger studies are needed, our findings provide an important rationale for continuing to evaluate TRT as a treatment for men who have received radical prostatectomy."
Approximately 50 to 70% of men treated with radical prostatectomy will experience sexual and physical dysfunction and nearly a third will have hypogonadism, a condition where the testes produce little to no testosterone. TRT has been shown to improve symptoms in men without a history of prostate cancer, but this trial—known as the Improving Quality of Life in Prostate Cancer Survivors with Androgen Deficiency (SPIRIT) study—is the randomized controlled trial to test TRT's safety and efficacy among prostate cancer survivors.
SPIRIT was conducted at Johns Hopkins Hospital and Brigham and Women's Hospital, a founding member of the Mass General Brigham healthcare system. The study enrolled men 40 years and older who had undetectable prostate-specific antigen (PSA) levels for at least two years after radical prostatectomy, and testosterone deficiency. For the trial, 136 participants were randomized to receive an injection of testosterone or a placebo once a week for 12 weeks and followed for an additional 12 weeks.
TRT significantly increased sexual activity, sexual desire, and quality of life scores. It also improved body composition, aerobic performance, and wellbeing. Erectile function did not change. No one in the TRT or placebo group experienced biochemical recurrence (a rise in PSA levels that indicates cancer's recurrence) during the study. The researchers recommend follow-up studies to continue evaluating long-term safety.
Authorship: In addition to Bhasin, Mass General Brigham authors include Thiago Gagliano-Jucá, Thomas W. Storer, Kieran F. Reid, Yili Valentine Shang, Fabiola Privat, Mohan S. Chandra, Mary Weiss, Yusnie Memish-Beleva, Helen Lam, Adam S. Kibel, and Karol M. Pencina. Additional authors include Arthur L. Burnett from the Johns Hopkins Medical Institute in Baltimore, MD.
Disclosures: Bhasin reported grants from the National Institute of Child Health and Human Development; National Institute of Diabetes and Digestive and Kidney Diseases; AbbVie; and Metro International Biotech; consulting fees from Arvinas, Besins, and Pfizer; and equity interest in Xyone outside the submitted work; in addition, Bhasin had a patent for TruT issued for method to estimate free testosterone. Additional author disclosures can be found in the paper.
Funding: The study was funded by a National Institute on Aging (NIA) grant (R01AG060539-05); additional support was provided by the infrastructural resources of the Boston Claude D. Pepper Older Americans Independence Center (P30AG031679).
Paper cited: Bhasin S et al. "Testosterone Treatment in Prostate Cancer Survivors With Hypogonadism A Randomized Clinical Trial" JAMA Internal Medicine DOI: 10.1001/jamainternmed.2026.1343
