Get started – check your testosterone

Dr Doug Savage
Dr Doug Savage
MBChB, MRCGP
Medical director

For decades, there have been concerns about the effect of TRT on prostate health – but how significant are these risks, if at all?

In this article, we break down the latest evidence to give you a clear overview.

Contents

How does testosterone affect the prostate?

Nowadays, there is no evidence from studies to suggest that TRT increases the risk of prostate cancer.

In the past, research seemed to show that increasing levels of testosterone may lead to or worsen prostate cancer. This was based on a study in the 40s. They found that lowering testosterone levels caused advanced prostate cancer to regress. They also concluded that injecting testosterone “activated” prostate cancer [1]. But we now know this isn’t the case.

Here’s what we know based on current research:

  1. TRT doesn’t increase the risk of prostate cancer – The fear of prescribing TRT and prostate cancer risk is based on an old concept of tumour prostate cells being sensitive to testosterone. This theory has been updated. As it stands, the latest evidence suggests that TRT does not increase the risk of prostate cancer [8–11].
  1. Higher testosterone levels don’t increase the risk of prostate cancer – While very low testosterone levels are linked to a lower risk of prostate cancer, studies have found that higher levels aren’t linked to an increased risk [3–5]. This is probably due to the “saturation model”. Once all the testosterone receptors are saturated with testosterone (at around 8 nmol/L), there’s likely no further effect of testosterone on prostate cancer risk [6]. For the minority of men with testosterone levels less than 8 nmol/L, this might explain why prostate-specific antigen (PSA) may increase when starting TRT [7].
  1. Very low testosterone levels may reduce the risk of prostate cancer but may increase the risk of more aggressive cancers – A study of around 19,000 men found that men with lower testosterone levels had a lower risk of prostate cancer. But if they did develop prostate cancer, they were more likely to develop a more aggressive form of the disease [2]. Another study that looked at over 8,000 men in the REDUCE trial also suggested that low baseline testosterone levels were linked to the lowest prostate cancer risk, but not disease severity [3].
  1. TRT may uncover a prostate cancer that’s already there by increasing PSA levels – Older men with low testosterone levels are more likely to develop prostate cancer that isn’t detectable with a PSA blood test. That’s because PSA levels tend to be lower in men with testosterone deficiency. TRT may raise PSA levels and unmask a cancer that was already there [12].

Do I need a prostate exam before starting TRT?

Although TRT is unlikely to have a detrimental impact on your prostate health, guidelines recommend some form of initial prostate assessment and monitoring as a caution.

The British Society for Sexual Medicine (BSSM) advises that a prostate examination or a prostate-specific antigen (PSA) blood test should ideally be carried out before starting TRT [7]. This is to exclude prostate enlargement or cancer. After that, they advise an annual PSA blood test. 

Leger recommendations

Before starting TRT, Leger advises the following prostate screening approach:

  • For men under 40 – a PSA or prostate examination isn’t usually necessary, because the risk of prostate cancer is negligible. The risk only starts to increase from the 40s onwards.
  • For men over 40 – a PSA level is required and preferably a prostate examination (especially if you’re high-risk for prostate cancer or over 60). A prostate examination is usually performed by the GP.

High-risk individuals include black men and men with a family history of prostate cancer (particularly close relatives who were diagnosed before the age of 60).

Can I take TRT if I have prostate enlargement (BPH)?

The FDA has previously stated that TRT for men with benign prostatic hypertrophy (BPH) may worsen symptoms of the condition.

However, more recent research shows that TRT is unlikely to worsen BPH and may even improve symptoms in some cases [13–16]. Therefore, TRT may be used with caution for men with BPH, particularly where the benefits outweigh the potential risks, but we still need more evidence to prove its safety.

Testosterone deficiency itself is also an important risk factor for benign prostatic hypertrophy (BPH) and associated urinary symptoms.

Can I take TRT if I have active prostate cancer?

Guidelines differ in their recommendations when it comes to TRT administration and active prostate cancer – and that’s mainly due to insufficient evidence.

A review of 36 studies and nearly 2,500 testosterone-treated patients found that TRT was not associated with disease progression in prostate cancer [17]. However, these were lower-quality studies. It also suggested that TRT could be harmful in men with advanced disease.  

As such, some guidelines advise against TRT for men with active prostate or, at the very least, advise taking a case-by-case approach involving a urology specialist and close monitoring [18, 19]. As with most medical treatments, the choice depends on several factors, including experts’ recommendations, the patient’s decision, and the risk-benefit ratio.

Can I take TRT if I’ve been treated for prostate cancer?

Men who have been previously treated for prostate cancer and have no evidence of active disease may be suitable for TRT [9, 20, 21].

We still need more trials investigating the effect of TRT in men treated for prostate cancer, but the risk in these scenarios is thought to be low.

Does taking TRT increase PSA levels?

TRT may increase PSA levels. Therefore, TRT prescribers have to consider whether an increase is within the expected range or sufficiently higher to warrant further investigation.

In some cases, TRT can unmask underlying prostate cancer by increasing PSA levels. However, it’s common for PSA levels to be falsely raised, which can lead to investigations or biopsies that aren’t needed.


How can I check my prostate health?

As part of your eligibility work-up for TRT, Leger will arrange a comprehensive blood test with you that includes PSA for a measure of your prostate health. They may also recommend a digital rectal examination if it's appropriate. 

The bottom line

Recent studies looking at the effects of TRT on prostate health are reassuring.

It’s still important to monitor your prostate throughout treatment, but the good news is that TRT doesn't increase your risk of prostate cancer.

References

  1. Huggins C, Hodges CV. The Effect of Castration, of Estrogen and of Androgen Injection on Serum Phosphatases in Metastatic Carcinoma of the Prostate*. Cancer Res. 1941;1: 293–7.
  2. Watts EL, Appleby PN, Perez-Cornago A, Bueno-de-Mesquita HB, Chan JM, Chen C, et al. Low Free Testosterone and Prostate Cancer Risk: A Collaborative Analysis of 20 Prospective Studies. European Urology. 2018;74: 585–594. doi:10.1016/j.eururo.2018.07.024
  3. Muller RL, Gerber L, Moreira DM, Andriole G, Castro-Santamaria R, Freedland SJ. Serum testosterone and dihydrotestosterone and prostate cancer risk in the placebo arm of the Reduction by Dutasteride of Prostate Cancer Events trial. Eur Urol. 2012;62: 757–764. doi:10.1016/j.eururo.2012.05.025
  4. Fernández-Balsells MM, Murad MH, Lane M, Lampropulos JF, Albuquerque F, Mullan RJ, et al. Clinical review 1: Adverse effects of testosterone therapy in adult men: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2010;95: 2560–2575. doi:10.1210/jc.2009-2575
  5. Bhasin S, Travison TG, Pencina KM, O’Leary M, Cunningham GR, Lincoff AM, et al. Prostate Safety Events During Testosterone Replacement Therapy in Men With Hypogonadism: A Randomized Clinical Trial. JAMA Network Open. 2023;6: e2348692. doi:10.1001/jamanetworkopen.2023.48692
  6. Kaplan AL, Hu JC, Morgentaler A, Mulhall JP, Schulman CC, Montorsi F. Testosterone Therapy in Men With Prostate Cancer. Eur Urol. 2016;69: 894–903. doi:10.1016/j.eururo.2015.12.005
  7. Hackett G, Kirby M, Rees RW, Jones TH, Muneer A, Livingston M, et al. The British Society for Sexual Medicine Guidelines on Male Adult Testosterone Deficiency, with Statements for Practice. World J Mens Health. 2023;41: 508–537. doi:10.5534/wjmh.221027
  8. Dohle G, Arver S, Bettocchi C, Jones T, Kliesch S. European Association of Urology (EAU) guidelines on male hypogonadism. European Association of Urology (EAU) guidelines. Arnhem; 2018. Available: https://uroweb.org/guideline/male-hypogonadism/
  9. Khera M, Adaikan G, Buvat J, Carrier S, El-Meliegy A, Hatzimouratidis K, et al. Diagnosis and Treatment of Testosterone Deficiency: Recommendations From the Fourth International Consultation for Sexual Medicine (ICSM 2015). J Sex Med. 2016;13: 1787–1804. doi:10.1016/j.jsxm.2016.10.009
  10. Dean JD, McMahon CG, Guay AT, Morgentaler A, Althof SE, Becher EF, et al. The International Society for Sexual Medicine’s Process of Care for the Assessment and Management of Testosterone Deficiency in Adult Men. J Sex Med. 2015;12: 1660–1686. doi:10.1111/jsm.12952
  11. Santella C, Renoux C, Yin H, Yu OHY, Azoulay L. Testosterone Replacement Therapy and the Risk of Prostate Cancer in Men With Late-Onset Hypogonadism. Am J Epidemiol. 2019;188: 1666–1673. doi:10.1093/aje/kwz138
  12. Bhasin S, Singh AB, Mac RP, Carter B, Lee MI, Cunningham GR. Managing the Risks of Prostate Disease During Testosterone Replacement Therapy in Older Men: Recommendations for a Standardized Monitoring Plan. Journal of Andrology. 2003;24: 299–311. doi:10.1002/j.1939-4640.2003.tb02676.x
  13. Baas W, Köhler TS. Testosterone replacement therapy and voiding dysfunction. Translational Andrology and Urology. 2016;5: 89097–89897. doi:10.21037/tau.2016.08.11
  14. Rizzuti A, Stocker G, Santos HO. Exploring the Role of Testosterone Replacement Therapy in Benign Prostatic Hyperplasia and Prostate Cancer: A Review of Safety. Uro. 2022;2: 30–39. doi:10.3390/uro2010005
  15. Kohn TP, Mata DA, Ramasamy R, Lipshultz LI. Effects of Testosterone Replacement Therapy on Lower Urinary Tract Symptoms: A Systematic Review and Meta-analysis. Eur Urol. 2016;69: 1083–1090. doi:10.1016/j.eururo.2016.01.043
  16. Jarvis TR, Chughtai B, Kaplan SA. Testosterone and benign prostatic hyperplasia. Asian J Androl. 2015;17: 212–216. doi:10.4103/1008-682X.140966
  17. Kim M, Byun S-S, Hong SK. Testosterone Replacement Therapy in Men with Untreated or Treated Prostate Cancer: Do We Have Enough Evidences? World J Mens Health. 2021;39: 705–723. doi:10.5534/wjmh.190158
  18. Jayasena CN, Anderson RA, Llahana S, Barth JH, MacKenzie F, Wilkes S, et al. Society for Endocrinology guidelines for testosterone replacement therapy in male hypogonadism. Clin Endocrinol (Oxf). 2022;96: 200–219. doi:10.1111/cen.14633
  19. Bhasin S, Brito JP, Cunningham GR, Hayes FJ, Hodis HN, Matsumoto AM, et al. Testosterone Therapy in Men With Hypogonadism: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2018;103: 1715–1744. doi:10.1210/jc.2018-00229
  20. Natale C, Carlos C, Hong J, Khera M, Baum N, Raheem OA. Testosterone Therapy After Prostate Cancer Treatment: A Review of Literature. Sexual Medicine Reviews. 2021;9: 393–405. doi:10.1016/j.sxmr.2020.12.003
  21. Kardoust Parizi M, Abufaraj M, Fajkovic H, Kimura S, Iwata T, D’Andrea D, et al. Oncological safety of testosterone replacement therapy in prostate cancer survivors after definitive local therapy: A systematic literature review and meta-analysis. Urologic Oncology: Seminars and Original Investigations. 2019;37: 637–646. doi:10.1016/j.urolonc.2019.06.007
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