Testosterone Therapy – What’s at the Heart of the Matter?

In men, there is a reason that Viagra is the largest selling drug in the world. As men age, their testosterone levels decrease, and with the availability of testosterone injections, topical patches and sprays, more and more men are asking their doctors to consider giving them “testosterone replacement therapy.” (TRT)

The FDA has noticed the dramatic increase in the number of prescriptions written. Earlier this year, the FDA issued a policy statement stating that testosterone treatment is only indicated for a small number of specific medical conditions, and that the use of TRT is of uncertain benefit and risks when used to treat the normal decline of testosterone levels with aging. In addition, there was notification of a possible increased risk of myocardial infarction and stroke.

Where has the medical world heard this kind of story before? When oral estrogens became easily available, it seemed very natural and appropriate that women should receive supplemental hormone therapy during and after menopause, to replace the “normal” levels that were present when they were younger. When long-term clinical randomized trails were conducted, only then did the data come forth indicating the significant risk of cardiovascular events and death in woman receiving estrogen supplements.

Regarding testosterone use, recent data indicate that 2.3 million prescriptions for a testosterone product were written in the United States in 2013, and the number is likely going to increase further. Many men are receiving TRT without even checking the testosterone level in the blood prior to starting the TRT!

TRT is indicated for some medical conditions, such as disorders of the pituitary gland or the testicles themselves. The failure of the testicles to make testosterone can be from genetic defects, or damage from chemotherapy or infection.

Research continues to accumulate about the potential cardiovascular effects of TRT. And the results differ from study to study! The earliest study was published in 2010 in the New England Journal of Medicine.[1] In this study of men over 65, the trial was stopped prematurely because of a significant increased incidence of cardiovascular events in the TRT group. Two other trials in 2013[2] and 2014[3]also found a significant increase in cardiovascular events and death in men with pre-existing cardiac disease receiving TRT.

More recent studies have not found a significant increase in cardiovascular risk in men without known heart disease, and in fact a study in the European Heart Journal found a decreased risk of cardiovascular events in men without known heart disease at the beginning of the study.[4]

 

So where does that leave patients and doctors in 2016? As is almost always the case in the practice of Medicine, a decision to start TRT must be an individualized decision between a patient and his doctor. From my perspective, in a patient with known heart disease or major risk factors for heart disease, such as diabetes, poorly controlled hypertension, hyperlipidemia, a cigarette smoker, and a family history of heart disease, I would not recommend TRT unless the patient has clear-cut symptoms of a documented low testosterone level. And in this situation, the patient needs to understand that the long-term data are not yet available and that increased cardiovascular risk is possible.

 

Even in patients without high cardiovascular risk who opt for a trial of TRT, close follow-up is necessary to see if the TRT helps with such matters as sexual performance, energy level, and bone density.

 

The bottom line – we don’t know if TRT helps most men, and we don’t know if TRT increases cardiovascular event rates. Not an attractive treatment option in 2016, but more data to come.

[1] Basaria S, Coviello AD, et al. “Adverse Cardiovascular Events Associated with Testosterone Administration.” New England Journal of Medicine 2010 363:109-122.

[2] Vigen, R , O’Donnell LI, et al. “Association of Testosterone Therapy with Mortality, Myocardial Infarction, and Stroke in Men with Low Testosterone Levels.” Journal of the American Medical Association 2013 370(17): 1829-1836.

[3] Finkle WD, Greenland S, et al. “Increased Risk of Non-Fatal Myocardial Infarction Following Testosterone Therapy in Men.” PLos ONE 9(1); e85805, January 29, 2014.

[4] Sharma R , Oni O, et al. “Normalization of Testosterone Levels is Associated with a Decreased Incidence of Myocardial Infarction and Mortality in Men.” European Heart Journal, online August 8 2015.

Author
Dr. Arnold Meshkov

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