TRT and Prostate Health: What You Need to Know About Testosterone and PSA Levels

Written by Adam Maggio | Medically reviewed by Dr. Mitchell Ross, MD, ABAARM

This article provides a comprehensive guide to TRT and Prostate Health: What You Need to Know About Testosterone and PSA Levels, covering essential aspects for practitioners and individuals. It delves into specific protocols and considerations for effective use.

Testosterone, Prostate Health, and PSA

The relationship between testosterone, prostate health, and prostate-specific antigen (PSA) levels has been a subject of considerable debate and concern, particularly for men considering or undergoing Testosterone Replacement Therapy (TRT). Historically, there was a widespread belief that testosterone fueled prostate cancer growth, leading to a cautious approach to TRT in men with prostate issues. This concern stemmed from early observations that androgen deprivation therapy (ADT) could shrink prostate tumors. However, modern research has significantly refined our understanding, revealing a more nuanced relationship. It is now largely accepted that in men without prostate cancer, TRT does not increase the risk of developing the disease. For men with existing prostate cancer, the situation is more complex and requires careful consideration [1].

TRT and Benign Prostatic Hyperplasia (BPH)

Benign Prostatic Hyperplasia (BPH) is a common, non-cancerous enlargement of the prostate gland that affects many aging men, leading to urinary symptoms such as frequent urination, weak stream, and nocturia. Testosterone plays a role in prostate growth, and thus, men with BPH often express concerns about TRT worsening their symptoms. Current evidence suggests that TRT does not significantly worsen BPH symptoms or increase prostate volume in men with pre-existing BPH, provided their testosterone levels are restored to a physiological range and not supraphysiological levels. The prostate appears to be saturated with androgens at relatively low testosterone concentrations, meaning that increasing testosterone from a hypogonadal to a eugonadal range does not typically lead to a disproportionate increase in prostate growth. However, men with severe BPH symptoms should be managed carefully, and their symptoms should be stable before initiating TRT. Medications for BPH, such as alpha-blockers (e.g., tamsulosin) or 5-alpha-reductase inhibitors (e.g., finasteride), can be used concurrently with TRT if needed [2].

TRT and Prostate Cancer Risk

The most significant concern regarding TRT and prostate health revolves around prostate cancer. Decades of research have largely debunked the myth that TRT causes prostate cancer. Multiple large observational studies and meta-analyses have found no increased risk of prostate cancer incidence in men receiving TRT compared to those not receiving it. The current understanding is that TRT does not initiate prostate cancer but can potentially accelerate the growth of pre-existing, undiagnosed microscopic prostate cancer. This is why thorough screening for prostate cancer is essential before initiating TRT, especially in older men. TRT is generally contraindicated in men with active prostate cancer. For men with a history of successfully treated prostate cancer (e.g., radical prostatectomy, radiation therapy), TRT may be considered in carefully selected cases, but this requires close collaboration between the urologist and the endocrinologist, with vigilant monitoring [3].

Prostate-Specific Antigen (PSA) Monitoring on TRT

PSA is a protein produced by prostate cells, and elevated levels can indicate prostate enlargement, inflammation, or cancer. Monitoring PSA is a critical component of TRT management:

• Baseline PSA: A baseline PSA level should be obtained before initiating TRT.
• Follow-up PSA: PSA should be re-checked at 3-6 months after starting TRT, and then annually thereafter.
• Interpretation: A modest increase in PSA (e.g., up to 0.4 ng/mL) after initiating TRT is common and generally not concerning, as restoring testosterone to normal levels can naturally increase prostate volume and PSA. However, a significant rise in PSA (e.g., >0.75 ng/mL in one year, or a PSA velocity that is concerning) or levels above age-specific norms should prompt further investigation, potentially including a urology referral, repeat PSA, or prostate biopsy.

It is important to remember that PSA is not a perfect marker for prostate cancer and can be influenced by many factors. Any concerning changes in PSA should be evaluated in the context of the patient's overall clinical picture and discussed with a urologist.

References

• [1] Morgentaler, A. (2006). Testosterone replacement therapy and prostate cancer. Urologic Clinics of North America, 33(4), 533-543.
• [2] Bhasin, S., et al. (2018). Testosterone Therapy in Men With Hypogonadism: An Endocrine Society Clinical Practice Guideline. Journal of Clinical Endocrinology & Metabolism, 103(5), 1715-1744.
• [3] Pastuszak, A. W., et al. (2013). Testosterone therapy in men with prostate cancer. Reviews in Urology, 15(4), 187-194.