Does Testosterone Replacement Therapy (TRT) stimulate the growth of cancer cells?

From the Guidelines

Testosterone Replacement Therapy (TRT) does not directly cause cancer, but it may potentially accelerate the growth of existing hormone-sensitive cancers, particularly prostate cancer. For this reason, men typically undergo prostate cancer screening before starting TRT, which includes a prostate-specific antigen (PSA) blood test and possibly a digital rectal exam. The relationship between testosterone and prostate cancer is complex; while high testosterone levels don't cause cancer, testosterone can stimulate growth in cancer cells that are already present and dependent on androgens for proliferation. This is why TRT is generally contraindicated in men with active prostate cancer or a history of the disease, as stated in the 2018 guidelines by the American Urological Association 1.

Some key points to consider when evaluating the risk of TRT and cancer include:

• The absence of evidence linking testosterone therapy to the development of prostate cancer, as noted in the 2018 AUA guidelines 1
• The importance of proper monitoring with measurement of PSA and digital rectal examination to promote the early diagnosis and potential cure of most "unmasked" prostate cancers identified during testosterone treatment, as discussed in the 2004 New England Journal of Medicine article 1
• The need for caution when considering TRT in men with a history of prostate cancer, as the risk-benefit ratio of testosterone therapy in these patients is not well established, according to the 2018 AUA guidelines 1

In terms of specific monitoring and treatment protocols, most men without pre-existing cancer can safely use TRT under proper medical supervision, which includes regular monitoring of PSA levels, hematocrit, and other relevant parameters. TRT is typically administered as injections (testosterone cypionate or enanthate, 50-200mg weekly or biweekly), daily transdermal gels (AndroGel, Testim), patches, or pellets implanted every 3-6 months, with dosing individualized based on symptoms and blood levels. Overall, the decision to start TRT should be made on a case-by-case basis, taking into account the individual patient's medical history, risk factors, and potential benefits and risks of treatment, as discussed in the 2004 New England Journal of Medicine article 1.

From the Research

Testosterone Replacement Therapy and Cancer Cell Growth

• The relationship between Testosterone Replacement Therapy (TRT) and cancer cell growth is a topic of ongoing research and debate.
• According to a review of the benefits and risks of TRT, there is no evidence to support the risk of stimulating prostate cancer by testosterone 2.
• A study of six cases of patients with high-risk prostate cancer who received TRT after high dose-rate brachytherapy found that all patients had slight increases in prostate-specific antigen (PSA) levels within the normal range, and no patients experienced disease recurrence or progression during TRT 3.
• A literature review on TRT and the risk of prostate cancer found that the current literature does not report a statistically significant increase in the development or progression of prostate cancer in men receiving testosterone replacement for symptomatic hypogonadism 4.
• A study of hypogonadal men with and without high-grade prostatic intraepithelial neoplasia (PIN) found that TRT did not increase the risk of cancer in men with PIN, and that PSA levels were similar at baseline and after 12 months of TRT in men with and without PIN 5.
• A randomized controlled trial is currently underway to determine the safety and efficacy of testosterone treatment in men who have undergone prostatectomy for non-aggressive prostate cancer and have symptomatic testosterone deficiency, with preliminary results showing no prostate-specific antigen or clinical recurrence to-date 6.

Key Findings

• TRT may not stimulate the growth of cancer cells, according to current research.
• PSA levels may increase slightly during TRT, but this does not necessarily indicate an increased risk of cancer.
• More research is needed to fully understand the relationship between TRT and cancer cell growth.
• Ongoing studies, such as the Surviving Prostate cancer while Improving quality of life through Rehabilitation with Testosterone Trial, aim to provide further insight into the safety and efficacy of TRT in men with a history of prostate cancer 6.