From the Guidelines
There is no evidence that testosterone replacement therapy (TRT) causes testicular cancer. TRT is generally considered safe when prescribed appropriately and monitored by healthcare providers. The medications used in TRT include testosterone injections (such as testosterone cypionate or enanthate), transdermal patches, gels (AndroGel, Testim), or pellets implanted under the skin, typically dosed to maintain testosterone levels within the normal physiological range of 300-1000 ng/dL. While TRT can cause side effects like acne, fluid retention, increased red blood cell production, sleep apnea, and breast enlargement, and may potentially worsen existing prostate cancer, it has not been linked to causing testicular cancer. In fact, men with a history of testicular cancer can often safely use TRT if they have low testosterone levels after treatment, as suggested by the ESMO-EURACAN clinical practice guideline for diagnosis, treatment, and follow-up of testicular seminoma and non-seminoma 1. The main testicular effect of TRT is actually suppression of natural testosterone production and potential shrinkage of the testicles due to reduced stimulation from pituitary hormones, but this is reversible upon discontinuation of therapy and does not increase cancer risk. Key considerations for the use of TRT in patients with a history of testicular cancer include:
- Regular hormonal assessments to monitor for hypogonadism 1
- Testosterone replacement therapy should only be offered to testicular cancer survivors with testosterone levels below the normal range and clinical symptoms of hypogonadism 1
- A healthy lifestyle should be encouraged for better well-being and minimization of cardiovascular disease and secondary cancers, which are the most serious long-term toxicities 1. It's also important to note that the most recent and highest quality study on this topic, published in 2022, does not suggest a link between TRT and testicular cancer 1.
From the Research
Testicular Cancer and Testosterone Replacement Therapy
- There is no direct evidence to suggest that testosterone replacement therapy (TRT) causes testicular cancer 2, 3, 4, 5, 6.
- The available studies focus on the relationship between TRT and prostate cancer, rather than testicular cancer.
- One study examined the effect of TRT on quality of life and sexual function in testicular cancer survivors with mild Leydig cell insufficiency, but it did not investigate the risk of developing testicular cancer 2.
- Other studies discussed the safety and efficacy of TRT in patients with prostate cancer, highlighting the lack of clear evidence that TRT promotes the development of prostate cancer 3, 4, 5, 6.
Key Findings
- TRT did not improve anxiety, depression, sexual function, fatigue, or overall quality of life in patients with mild Leydig cell insufficiency compared to placebo 2.
- Testosterone therapy is effective and does not appear to increase cancer recurrence rates in men with a history of prostate cancer 3.
- There is no clear evidence that elevations in endogenous testosterone levels promote the development of prostate cancer in humans 4.
- The use of TRT in prostate cancer patients is still considered experimental and should only be offered after well-informed shared decision making and with close monitoring 4, 5.
Limitations
- The available studies do not provide direct evidence on the relationship between TRT and testicular cancer.
- More research is needed to determine the safety and efficacy of TRT in patients with testicular cancer.