What is the relationship between testosterone and prostate cancer?

From the Guidelines

Testosterone therapy is generally safe for most men with a history of prostate cancer who have been successfully treated and show no evidence of active disease, as long as they are closely monitored. When considering testosterone replacement therapy (TRT) for these patients, it's essential to weigh the potential benefits of improved energy, libido, and quality of life against any risks. According to the most recent guidelines, men over 40 years of age should have their PSA levels measured prior to starting testosterone therapy to exclude a prostate cancer diagnosis 1.

Key Considerations

• Before initiating TRT, patients should undergo baseline PSA and digital rectal examination, with follow-up PSA monitoring every 3-6 months during the first year of treatment, then annually if stable.
• The standard TRT regimen includes options like testosterone cypionate or enanthate injections (50-200mg every 1-2 weeks), daily transdermal gels (50-100mg), or testosterone pellets (implanted every 3-6 months).
• Men who have undergone radical prostatectomy or radiation therapy and have undetectable PSA levels for at least 1-2 years can typically consider TRT under careful monitoring.
• TRT remains contraindicated in men with active, untreated prostate cancer or high-risk disease, as it may stimulate cancer growth in these cases.

Monitoring and Evaluation

• Patients who maintain on-treatment testosterone levels in the normal range should decide on PSA testing using a shared decision-making approach with their clinician, in accordance with the American Urological Association’s Early Detection of Prostate Cancer Guideline 1.
• For patients with elevated PSA levels at baseline, a second PSA test is recommended to rule out a spurious elevation, and a more formal evaluation, potentially including reflex testing and prostate biopsy with/without MRI, should be considered before initiating testosterone therapy.

Historical Beliefs and Modern Research

• The historical belief that testosterone "feeds" prostate cancer has been largely disproven by modern research, which shows that androgen receptors become saturated at relatively low testosterone levels 1.
• However, each patient's situation should be individually evaluated, taking into account their unique medical history and potential risks and benefits of TRT.

From the FDA Drug Label

Men with carcinoma of the breast or known or suspected prostate cancer. (4,5.1)

• Testosterone is contraindicated in men with known or suspected prostate cancer.
• The use of testosterone in patients with a history of prostate cancer is not recommended due to the potential for exacerbating the disease.
• Prostate cancer is a contraindication for testosterone therapy, as stated in the drug label 2.

From the Research

Testosterone and Prostate Cancer Relationship

• The relationship between testosterone and prostate cancer has been a topic of discussion, with some studies suggesting that higher testosterone levels may not necessarily cause enhanced growth of prostate cancer 3.
• Testosterone replacement therapy (TRT) has been considered taboo for men with a prior history of prostate cancer, but some studies have shown that TRT does not pose an increased risk of prostate cancer growth in men with or without prior treatment 3, 4.

Testosterone Replacement Therapy in Prostate Cancer Survivors

• Some studies have investigated the safety and efficacy of testosterone replacement therapy in prostate cancer survivors with testosterone deficiency, with results showing no significant increase in cancer recurrence rates 4, 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 5.

Prostate Cancer Screening and Diagnosis

• Prostate cancer screening via prostate-specific antigen testing may lead to a small reduction in prostate cancer-specific mortality, but it can also cause significant harms related to false-positive test results and overdiagnosis 6.
• Shared decision-making is strongly recommended before initiating screening, and most guidelines recommend screening every 2 to 4 years in men 55 to 69 years of age at average risk 6.

Exercise and Prostate Cancer

• Exercise has been shown to influence cancer risk, and epidemiological studies have suggested that total physical activity is related to a decrease in the risk of developing prostate cancer 7.
• Exercise may also counteract several side effects of androgen deprivation therapy, including loss of libido, changes in body composition, and reduced muscle mass and muscle tone 7.