risks associated with testosterone treatment

by Chris Steidle, MD.

As with all therapies, there are benefits and risks associated with treatment. Testosterone replacement therapy (TRT) has been used to treat low levels of testosterone for more than fifty years and many clinical studies have shown that, in general, men tolerate it very well. ^{1, 2} However, this treatment may have a few risks associated with it even though they are rare.

Prostate Cancer

Testosterone may worsen the effects of prostate cancer in some men, which is why it is highly recommended that you have a baseline PSA (prostate specific antigen - a substance that increases in men with prostate cancer) test before starting treatment. If there is any possibility that you have prostate cancer, which is more prevalent in older men, you should avoid using testosterone treatments.

There have been many studies done to understand the relationship between TRT and prostate cancer, specifically whether it can actually cause prostate cancer. While it has been shown that testosterone has a worsening effect on existing prostate cancer, the prevailing opinion is that restoring testosterone to normal levels does not appear to increase the risk of carcinoma. Due to the conflicting results of the studies, no conclusive evidence exists of a relationship between serum testosterone and prostate cancer ³.

Many studies have also been done on the effect of supplemental testosterone on PSA level but, "due to the lack of agreement in the study results, no relationship between serum testosterone and PSA was established."⁴ Nevertheless, it is important to test PSA levels on a regular basis while using TRT.

Increased hemoglobin and hematocrit readings (red blood cells)

Testosterone may tend to cause an increase in red blood cells, especially in older men. Most of the time, this is a welcome development since the increased oxygen carrying capacity of the blood may contribute to improved energy levels and less fatigue. In some men, however, the increase may be large enough to warrant ending the treatment, removing blood (as in donating blood) or decreasing the dose of testosterone. The effect seems to occur more often in men who receive testosterone through injections or pellets, presumably because of the extremely high levels achieved immediately after treatment. Switching to another delivery method that provides a more uniform testosterone level, such as occurs with patches and gels, may be all that is needed.

Male breast enlargement and tenderness

Some men on testosterone therapy develop enlarged or tender breasts, especially older men who tend to have more fat in this area. Fat cells contain enzymes that can convert testosterone into a female hormone, estradiol, which happens when the testosterone level is raised above normal. This is more likely to happen with delivery methods that cause large fluctuations in testosterone levels (injections and pellets) than with patches and gels that tend to maintain a constant level over time.

Precipitation or worsening of sleep apnea

Various studies have shown that testosterone supplementation may worsen pre-existing sleep apnea.⁵ Others have shown that some men with sleep apnea have low testosterone levels that normalize when the sleep apnea is treated.⁶ Obviously, the relationship between testosterone and sleep apnea is still poorly understood. In any case, if you have sleep apnea, you should discuss treatment for this condition with your doctor before you try TRT.

¹ The Endocrine Society.
² Mayo Foundation for Medical Education and Research.
³ Brawer, MK. Androgen Supplementation and Prostate Cancer Risk: Strategies for Pretherapy Assessment and Monitoring. Urol. 2003;5(suppl 1):S29-S33.
⁴ Brawer, MK. Androgen Supplementation and Prostate Cancer Risk: Strategies for Pretherapy Assessment and Monitoring. Urol. 2003;5(suppl 1):S29-S33.
⁵ Matsumoto AM, Sandblom RE, Schoene RB, et al. Testosterone replacement in hypogonadal men: effects on obstructive sleep apnea, respiratory drives and sleep. Clin Endocrinol (Oxf). 1988;28:461-470.
⁶ Santamaria JD, Prior JC, Fleetham JA. Reversible reproductive dysfunction in men with obstructive sleep apnea. Clin Endocrinol (Oxf). 1988;28:461-470.

Next article in this series: monitoring treatment

Last updated: June 2003