What did the JAMA study find about testosterone therapy?

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Journal of American Medical Association study: low-T therapy may be harmful

Even though the effects of testosterone therapy on cardiovascular health and mortality are unknown, more American men are getting prescriptions for testosterone therapy drugs. From 2000 to 2011, annual prescriptions for testosterone surged more than 500%.

A 2010 medical study into the effects of testosterone therapy was halted prematurely due to the significant rate of adverse cardiovascular events among the study’s participants, which raised concerns about the safety of testosterone therapy. Due to uncertainty regarding the efficacy and safety of testosterone replacement therapy, a group of doctors investigated the association between testosterone therapy and death, heart attack, and stroke among male veterans and published their findings in the Journal of the American Medical Association (JAMA).

The JAMA study investigated male veterans who received medical care at a Veterans Affairs (VA) Hospital between 2005 and 2011 and had their testosterone level checked. VA Hospitals use custom software to collect patient and procedure data. This data culled from VA laboratory files was the source for the JAMA testosterone therapy study. Unlike the 2010 study, which used Testim testosterone gel, the JAMA study looked into the use of testosterone gel, patch, and injections and the association with death, myocardial infarction (heart attack), percutaneous intervention (angioplasty), coronary artery bypass graft, and stroke.

The subjects of the retrospective observational study were 8,709 men who underwent coronary angiographies at VA hospitals between 2005 and 2011 and had their testosterone level checked. The survival curves comparing men who took testosterone therapy with those who did not found that testosterone use was associated with an increased risk of death, myocardial infarction (heart attack), and stroke. Adjusting for the presence of coronary artery disease in the study’s subjects did not change the findings.

Of the study subjects, 1.1% were prescribed a testosterone gel, 35.7% received testosterone injections, and 63.3% received testosterone patches. The study did not find a difference in the risk of health problems between the different forms of testosterone formulations.

The study found that the use of testosterone replacement therapy was “significantly associate with adverse outcomes despite the lower prevalence of [health problems] in the testosterone therapy group,” which “raises concerns about the potential safety of testosterone therapy.”

The study notes several ways that testosterone may increase cardiovascular risk:

  • Intramuscular testosterone has been associated with an increase in platelet density, which may play a role in coronary plaque formation.
  • Lab studies have found that a product produced by metabolizing testosterone can promote the thickening of artery walls.
  • Testosterone therapy has been shown to aggravate sleep disordered breathing among patients with severe sleep apnea, which can raise the risk of thickening artery walls

The JAMA testosterone study notes that it has some limitations including that the study was performed on men undergoing angiography in the VA system, many of whom had health problems, the study not take into account the time of day the testosterone levels were measured (testosterone levels change throughout the day), and the study only examined a relatively small group of patients with extended follow-up times. Nevertheless, the JAMA study found that the long-term risks associated with testosterone therapy are unknown and the possibility exists that low-T therapy may be harmful.

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