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testosterone therapy: risks

by Chris Steidle, MD

Testosterone therapy, as with all treatments, carries some risks along with its benefits. 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, testosterone treatment may have a few risks associated with it even though they are rare.

Prostate cancer and testosterone therapy

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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 testosterone 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 testosterone treatment and prostate cancer, specifically whether testosterone 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 testosterone replacement therapy.

Increased hemoglobin and hematocrit readings (red blood cells) with testosterone treatment

Testosterone treatment 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 testosterone 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 with testosterone treatment

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 with testosterone treatment

Various studies have shown that testosterone therapy 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 testosterone replacement therapy.

All of these risks point out the importance of working with a knowledgeable doctor when thinking about or using testosterone therapy.

References

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.

Posted February 2004
Updated August 2009

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