Miller School Trial Tests Testosterone Therapy in Men With Low-Risk Prostate Cancer
Researchers are evaluating whether weekly testosterone cypionate injections can be used safely in carefully selected men with low-risk prostate cancer who are undergoing active surveillance.
Researchers at the University of Miami Miller School of Medicine are launching a first-of-its-kind prospective clinical trial to evaluate the safety of testosterone cypionate injections in men with low-risk prostate cancer who are being monitored through active surveillance rather than receiving immediate treatment.
Led by Bruce Kava, M.D., professor of urology and director of men’s health at the Desai Sethi Urology Institute (DSUI), the study aims to address this gap that could impact how physicians approach testosterone deficiency in men with low-risk prostate cancer.
“Active surveillance is about safely managing low-risk prostate cancer while preserving quality of life,” said Sanoj Punnen, M.D., professor of urologic oncology at the Miller School and DSUI vice chair of research. “For some men, maintaining quality of life may include testosterone supplementation. While historical dogma raised concerns about testosterone use in men with prostate cancer, many urologists now believe it can be used safely in carefully selected men on active surveillance with appropriate monitoring. The challenge is that we still lack high-quality prospective data to know this with certainty. This trial is designed to help provide that evidence and better inform how we counsel and care for these men.”
Why This Research Matters
- Low testosterone affects an estimated 20-25% of men over age 55.
- Many men with low-risk prostate cancer are currently excluded from testosterone replacement.
- This is among the first prospective studies to evaluate testosterone therapy in men on active surveillance.
- Findings could influence future treatment guidelines and quality-of-life discussions.
Why Study Testosterone Therapy During Active Surveillance?
Active surveillance has become a widely accepted strategy for managing low-risk prostate cancer. Rather than immediately pursuing surgery or radiation, patients undergo regular PSA testing, MRI imaging and periodic biopsies to monitor whether their cancer progresses. The approach helps many men avoid treatment-related side effects while maintaining cancer control.
At the same time, testosterone deficiency can significantly affect quality of life, including reduced energy, diminished sexual function, mood changes, decreased vitality and loss of bone density.
“Testosterone deficiency has very profound physical and psychological effects on men,” Dr. Kava said.
How the Study Works
The prospective, single-arm pilot study will enroll up to 35 men with newly diagnosed low-risk prostate cancer and documented hypogonadism who are currently undergoing active surveillance. Participants must have two testosterone measurements below 300 ng/dL, symptoms consistent with testosterone deficiency and confirmatory biopsy findings demonstrating low-risk disease.
Eligible participants will receive 100 milligrams of testosterone cypionate through weekly intramuscular injections and will be followed closely for 12 months. Researchers will continue collecting progression and survival data for up to five years. The research team intentionally selected testosterone cypionate because it reflects how testosterone replacement is commonly delivered in real-world clinical practice.
“Most men do not use testosterone gel. They use testosterone cypionate injections because of the lower cost, the ease of administration and the lack of transference of the medication to their partners, children and others,” Dr. Kava said.
Unlike testosterone gels, which provide lower but more stable hormone levels, testosterone cypionate produces higher peaks that gradually decline between injections. Those fluctuations have led some clinicians to theorize that injectable testosterone could carry greater risk.
“The fluctuation of the levels into the higher ranges may make testosterone cypionate theoretically more risky,” Dr. Kava said. “We think that, since most patients use this manner of administration, it should be studied more rigorously.”
How Will Researchers Monitor Prostate Cancer Progression?
One of the key methodological challenges involves distinguishing routine hormonal effects from signs that cancer is worsening. Because testosterone therapy can cause an initial increase in prostate-specific antigen (PSA), participants will undergo regular PSA, testosterone and hematocrit monitoring, along with multiparametric MRI and repeat biopsies, allowing researchers to distinguish expected hormonal changes from signs of disease progression rather than relying on PSA alone.
“We will use a number of techniques,” Dr. Kava said. “PSA is expected to increase slightly once testosterone is administered, but it generally will level off.”
The study’s primary endpoint is disease progression within 12 months, defined as either worsening cancer grade on biopsy or conversion from active surveillance to active treatment. Outcomes will be compared with historical data from the Miami Active Surveillance Trial (MAST).
Frequently Asked Questions
Does testosterone therapy cause prostate cancer?
Current evidence suggests testosterone therapy does not cause prostate cancer. However, whether it can be safely used in men with untreated low-risk prostate cancer remains an active area of research.
What is active surveillance for prostate cancer?
Active surveillance involves closely monitoring low-risk prostate cancer through PSA testing, MRI scans and repeat biopsies rather than immediately treating the cancer with surgery or radiation.
Why are men with prostate cancer often denied testosterone therapy?
Historically, physicians believed testosterone could fuel cancer growth. More recent research has challenged that assumption, but definitive prospective data remain limited.
What is the goal of the study?
Researchers aim to determine whether testosterone cypionate can safely improve symptoms of low testosterone without accelerating prostate cancer progression.
What Could the Study Clarify for Patients and Physicians?
If the study demonstrates that testosterone replacement can be administered safely in carefully selected men on active surveillance, the findings could have significant implications for patient care.
According to Dr. Kava, the potential benefits extend well beyond symptom relief. Patients could experience improvements in “sexual function, vitality, bone health and cardiovascular risk factors,” he said.
The study may also contribute evidence to support future guideline modifications. While the FDA has already acknowledged that testosterone therapy does not cause prostate cancer, questions remain about its role in men with untreated disease. Dr. Kava believes the trial could help fill that evidence gap.
Success, he said, would mean demonstrating that testosterone cypionate administration is “safe and effective in low-risk patients with Gleason’s 6 prostate cancer who are currently on active surveillance” and that there is “no evidence that it exacerbates existing prostate cancer in this cohort.”
For thousands of men living with both low-risk prostate cancer and testosterone deficiency, the results could help redefine a long-standing clinical dilemma and potentially expand treatment options that improve quality of life without compromising cancer control.
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Tags: active surveillance, cancer research, Department of Urology, Desai Sethi Urology Institute, Dr. Bruce Kava, Dr. Laura Angulo Llanos, Dr. Sanoj Punnen, men's health, prostate cancer, Sylvester Comprehensive Cancer Center, testosterone deficiency, urology