Testosterone & Hypogonadism

Testosterone Replacement Therapy and Prostate Cancer: Is There a Link?


Zoe Miller, BSc, MD, MBChB
February 16, 2024
Take-home points
  • In a study of 5204 men with hypogonadism, testosterone replacement therapy didn’t significantly increase the risk of prostate cancer.
  • 92% of men were followed up for 1 year, 74% for 2 years, 57% for 3 years, and 1.6% for 4 years.  
  • The study only included men with a normal or low risk of prostate cancer.

Testosterone replacement therapy and prostate cancer

A new study in JAMA Network Open investigated whether testosterone replacement therapy increases the risk of prostate cancer.1

What is the prostate?

The prostate is a male-specific gland, about the size of a walnut, that’s found underneath the bladder. It’s important for the production of semen – not the sperm, but the liquid itself.

What is prostate cancer?

Prostate cancer is an abnormal, uncontrolled growth of cells in the prostate. Prostate cancer is different to a benign enlarged prostate, where the prostate gets larger, but the cells aren’t cancerous.

PSA is a protein that’s produced by the prostate. A larger prostate produces more PSA, so PSA levels in the blood are commonly tested to check for prostate cancer or a benign enlarged prostate. Prostate cancer is also confirmed through examination, other blood tests, and biopsy.

Learn more about the use of PSA testing for ProstateCancer

What is testosterone replacement therapy (TRT)?

Testosterone replacement therapy(TRT) is a type of artificial testosterone that’s given when natural testosterone levels are low. Most commonly, this is due to hypogonadism.  Learn more about hypogonadism here.

Why do men take testosterone replacement therapy?

The aim of TRT is to get testosterone levels in the blood back to within the normal range. This means you might need regular blood tests and changes to your testosterone dose. TRT can help improve the symptoms of low testosterone, like poor libido, erectile dysfunction, hair loss, and reduced energy levels. It’s available in a variety of forms, including tablets, and injections, or it can be applied directly to the skin.

Why investigate testosterone replacement therapy and prostate cancer?

When prescribing TRT for men with hypogonadism, doctors may be worried about increasing a man’s risk of prostate cancer. Some evidence suggests men with low testosterone are at decreased risk of prostate cancer 2 and that higher levels of testosterone3 in the blood are linked to prostate cancer. But other studies have found that TRT can reduce the risk of prostate cancer.4 Read more about the relationship here. Researchers wanted a clearer answer, so they investigated using data from the biggest clinical trial on TRT.

Study title:

  • Prostate Safety Events During TestosteroneReplacement Therapy in Men With Hypogonadism: A Randomized Clinical Trial

What did they do?

In this study, 5,204 men aged 45–80 applied 1.62% testosterone gel (or a placebo gel) to their skin every day. The dose was changed to keep blood testosterone levels between 350 and 750 ng/dL, or doctors pretended to adjust the dose in the placebo group. The men were then monitored for signs of prostate cancer, an enlarged prostate, and urinary symptoms like being unable to urinate (urinary retention).1

To be included in the study, men had to have:

  • Low testosterone (2 morning blood readings below 300 ng/dL).
  • Hypogonadal symptoms.*
  • A cardiovascular disease** or risk factor.***
  • A normal sized prostate for their age (based on PSA and IPSS scores).

This study was part of the Testosterone Replacement Therapy for Assessment of Long-Term VascularEvents and Efficacy Response in Hypogonadal Men (TRAVERSE) study.5

What did they find?

There was no significant difference in the study outcomes (number of men who developed prostate cancer, urinary retention, or an enlarged prostate needing surgery) between the TRT and placebo groups.

Although PSA levels (blood marker of an enlarged prostate) increased more in the TRT group, the increase was small.

Summary of patient prostate and urinary outcomes

The number of men with urinary symptoms needing new medication during the trial was also not significantly different between the two groups. 

What are the study conclusions?

In summary, the study found that testosterone replacement therapy did not increase the risk of prostate cancer or the risk of prostate-relatedurinary symptoms during the follow up period.

How should we interpret this data?

This study suggests that TRT doesn’t significantly increase the risk of prostate cancer. However, it’s unclear whether this is the case in men who already have a high risk of prostate cancer. Generally, guidelines suggest avoiding TRT in men at an increased risk of prostate cancer.6,7 As this study only included men at normal risk of prostate cancer, the findings can’t necessarily be applied to men known to be at high risk or with prostate cancer. The study had some other limitations, including the short follow up period. Only 57.2% of men were followed up for 3 years, and just 1.4% for 4 years. This may not have been long enough to detect any significant differences in the rate of prostate cancer.

When looking at the differences between groups, the confidence intervals were very wide. A bigger range means more room for doubt, and that the sample may not represent the true population. Overall, the data from the study supports the use of testosterone replacement therapy in men with hypogonadism and a normal risk of prostate cancer. TRT doesn’t seem to increase the risk of prostate cancer in this population of men, at least during the following period of this study, which is consistent with previous data. 


*Hypogonadal symptoms are symptoms of low testosterone, such as erectile dysfunction, reduced sex drive, and breast growth. 

**Cardiovascular diseases include heart disease, a previous stroke, or disease of the arteries in the legs.

***Cardiovascular risk factors include things like high cholesterol, smoking, high blood pressure, age, and diabetes.


1.     Bhasin S, et al. JAMA Netw Open 2023;6(12):e2348692. Available: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10753401/

2.    Prostate Cancer UK. Available from: https://prostatecanceruk.org/about-us/news-and-views/2017/11/testosterone-and-prostate-cancer-risk-the-plot-thickens

3.    Watts EL, et al. Int J Cancer2022;151(7):1033–46. Available from: https://pubmed.ncbi.nlm.nih.gov/35579976/

4.    Zhang X, et al. The Ageing Male 2020;23(2):112-118. Available from: https://pubmed.ncbi.nlm.nih.gov/30857458/

5.    Bhasin S, et al. American Heart Journal 2022;245:41-50. Available from: https://www.sciencedirect.com/science/article/pii/S0002870321004671

6.    Mulhall JP, et al. JUrol 2018;200(2):423-432. Availabe from: https://pubmed.ncbi.nlm.nih.gov/29601923/

7.    Bhasin S, et al.J Clin Endocrinol Metab 2018;103(5):1715-1744. Available from: https://pubmed.ncbi.nlm.nih.gov/29562364/

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