Testosterone and estrogen are primary sex hormones. Both men and women produce testosterone, but men make more. Testosterone is produced mainly by the testes, increases as a boy matures and is responsible for the maturity of sex organs, increased body and facial hair, muscle mass, and a deeper voice. It also promotes sperm production. Testosterone levels fluctuate over your lifespan but begin declining after age 30. This may result in less interest in sex later in life and possibly fewer firm erections, as well as softer muscle tone.

Hypogonadism is the condition that occurs when the body doesn’t produce enough testosterone on its own. Testosterone replacement therapy can be used to treat hypogonadism. The Endocrine Society recommends offering testosterone therapy to people with symptoms of testosterone deficiency. In men over 65, treatment should only be initiated on an individual basis and after consultation with the person regarding risks and benefits.1

Testosterone Supplements

Like other supplements and medications, testosterone therapy comes with risks and possible side effects. Testosterone supplements however might cause more problems than they solve. Studies have suggested a connection between supplements and heart problems and the use of testosterone replacement therapy may increase your risk for prostate cancer.2,3 This is particularly true if you try to take it for normal aging rather than to treat a condition. Other side effects of Testosterone supplements include enlarged breasts, sleep apnea, worsening acne and testicular shrinkage.

Testosterone and Prostate Cancer

Since it is known to stimulate the growth of some prostate cancers, effective treatments for prostate cancer include suppression of testosterone levels by surgical removal of the testes or treatment with testosterone-lowering drugs. Given this link between testosterone and prostate cancer, there is interest in understanding whether use of testosterone supplements to treat sexual dysfunction or for “rejuvenation” increases a man’s risk of prostate cancer. This is a particularly important question for older men, who are the most likely to receive testosterone supplements and most likely to have undetected prostate cancer that could be stimulated by testosterone.

Prostate Cancer Risk and Testosterone Supplements

While data from large, prospective, randomized, controlled trials are absent, the use of Testosterone supplementation in select prostate cancer patients is likely safe but still considered experimental and should only be offered after well-informed shared decision making and with close monitoring.

Some but not all research suggests that increased testosterone levels in men increases the risk of developing prostate cancer. Researchers from Baltimore conducted a clinical study to evaluate testosterone, as well as other male hormone levels in the blood of men, and the possible association to prostate cancer. The study included blood samples from 759 men; 111 of whom were diagnosed with prostate cancer. The blood was tested for levels of testosterone, sex hormone-binding globulin (SHBG), and dehydroepiandrosterone sulfate (DHEAS). In patients over the age of 55, testosterone levels in the blood were associated with the development of prostate cancer, with every unit of measure in the blood associated with nearly double the risk of prostate cancer. The researchers concluded that increased testosterone levels in the blood appear to be associated with an increased risk of developing prostate cancer in men aged 55 years and older. The researchers caution that men who take supplemental testosterone should discuss their individual risks and benefits of this type of hormone therapy with their physician.7

Researchers from the United Kingdom conducted a large study to evaluate a potential association between testosterone levels and prostate cancer. This study included data from 18 clinical studies that included 3,886 men who had been diagnosed with prostate cancer and 6,438 men who did not have prostate cancer. Data including levels of testosterone in the blood were compared between the two groups. Overall, there was no association between levels of testosterone and the rate of prostate cancer. The researchers concluded that there does not appear to be an association with the risk of developing prostate cancer and levels of testosterone circulating in the blood.8

Testosterone and Active Surveillance in Men with Early-Stage Prostate Cancer

Testosterone therapy (used to treat symptoms of testosterone deficiency) may not worsen prostate cancer in selected men undergoing active surveillance for early-stage disease.5 Symptoms of testosterone deficiency (low testosterone levels) include fatigue, decreased libido, and decreased sexual performance. Testosterone therapy can help to relieve these symptoms, but it’s generally not given to men with a history of prostate cancer because of concern that testosterone therapy may fuel prostate cancer growth. Other research, however, has raised the possibility that the maximal effect of testosterone on prostate cancer is reached at a fairly low level of testosterone, and that testosterone levels beyond this point do not further increase cancer growth.

To explore the effects of testosterone therapy on men with untreated prostate cancer, researchers evaluated 13 men who were undergoing active surveillance for early-stage prostate cancer. All of the men were receiving testosterone therapy for symptoms of testosterone deficiency. In order to detect changes in their prostate cancer, the men were monitored with prostate biopsies, prostate-specific antigen (PSA) tests, and measurement of prostate volume. Study participants received testosterone therapy for a median of 2.5 years after their prostate cancer diagnosis.

  • Testosterone therapy raised the average blood level of testosterone from 238 ng/ml to 664 ng/ml
  • Testosterone therapy did not appear to affect PSA level or prostate volume.
  • Two of the men had biopsy results that suggested that the cancer may be worsening (Gleason score increased from 6 to 7). Additional follow-up, however, did not confirm cancer progression.

Although this study was small, it raises the possibility that testosterone therapy may be safe for selected men with a history of prostate cancer. The researchers conclude “The longstanding prohibition against testosterone therapy in men with untreated or low risk prostate cancer or treated prostate cancer without evidence of metastatic or recurrent disease merits reevaluation.” An accompanying editorial recommends caution, noting “Although this approach is feasible, it is experimental at this point and patients should be appropriately cautioned.” Men who take testosterone supplements should be monitored regularly for prostate cancer.

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References:

1. https://www.endocrine.org/clinical-practice-guidelines/testosterone-therapy#2

2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3897047/

3. https://www.nejm.org/doi/full/10.1056/nejmoa1000485

4. Gaylis FD, Lin DW, Ignatoff JM et al. Prostate cancer in men using testosterone supplementation. The Journal of Urology. 2005;174:534-538.

5. Morgentaler A, Lipshultz LI, Bennett R, Sweeney M, Avila D, Khera M. Testosterone therapy in men with untreated prostate cancer. Journal of Urology. 2011;185:1256-1261.

6. Agarwal PK. Editorial comment. Journal of Urology. 2011;185:1261.

7. Parsons J, Carter H, Landis P, et al. Higher serum free testosterone is associated with an increased risk of prostate cancer: results from the Baltimore Longitudinal Study on Aging. Proceedings from the 99th annual meeting of the American Urological Association. 2004;171: Abstract #439.

8. Endogenous Hormones, Prostate Cancer Collaborative Group. Endogenous sex hormones and prostate cancer: a collaborative analysis of 18 prospective studies. Journal of the National Cancer Institute [published early online]. January 29, 2008. DOI: doi:10.1093/jnci/djm323.

9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4647137/

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