Does Testosterone Cause Heart Attacks? A Response To JAMA Study

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Dr. Josh Trutt

JAMA published a study today that looked at VA Hospital patients with low testosterone levels. The men were about 62 years old, and were given testosterone replacement therapy for about a year. But what the authors found was surprising: the men who got testosterone did worse than the men who didn’t! Specifically, they had a small increase in heart attacks and strokes. That doesn’t sound good!

It’s especially surprising since a very similar trial was published just last year in the Journal of Clinical Endocrinology and Metabolism and got exactly the opposite result!

That study also looked at male veterans, about the same age (average age 61), who also had very low testosterone. Those men got the same sort of intervention: testosterone either by injections or gel or patch, and they were tracked for about 43 months. (Today’s JAMA study only followed their patients for 28 months.) Here’s what the authors found in last year’s study:

The mortality in testosterone-treated men was 10.3% compared with 20.7% in untreated men
 (P <0.0001)!

Conclusions: In an observational cohort of men with low testosterone levels, testosterone treatment was associated with decreased mortality compared with no testosterone treatment.

The men who got testosterone had half the risk of death! That’s what I would expect to see. So what went wrong in today’s JAMA study??


First, some history:
It has for decades been known that low testosterone levels in men are bad: when your levels drop, you are at increased risk of death from all causes—and particularly from heart disease. Many studies have looked at this:
Click here to see a handful of studies showing that low testosterone levels are associated with heart disease and death.

In fact, cardiologists have studied testosterone as a treatment for coronary heart disease for over 70 years. The idea appeared in the New England Journal of Medicine way back in May 1942(!!), followed immediately by a series of case reports published in the Journal of Clinical Endocrinology and Metabolism, by Dr. L. Hamm.
Dr. Hamm reported:

[I] administered testosterone [injections] to 24 patients with angina pectoris in order to determine its influence on the frequency and/or severity of attacks. All patients improved as measured by diminution in frequency, duration, and severity of their anginal attacks and by their ability to increase physical activity without precipitating attacks. This improvement persisted for 2 to 12 months following interruption of therapy. Similar results did not follow injections of sterile sesame oil given as a control measure.2

Over the ensuing 70 years, many others have followed in Dr Hamm’s footsteps, with similar results. Click here to see other studies looking at testosterone injections in men with known coronary artery disease.

An excellent review of the literature was provided in 2012 by Morris and Channer, which can be seen in its entirety here: Testosterone and Cardiovascular Disease in Men


In light of all that, the JAMA results are surprising: Why did the same type of patients (VA Hospital patients around 61 years old) have great results in the testosterone study published last year– half the risk of death! — yet this year another study shows that giving them testosterone increased their risk of heart attacks and strokes?? Which study should we believe??

The answer is, maybe we can believe both studies– because even though both studies looked at men of about the same age and from the same type of treatment center, these two groups of men were very different.

The men in today’s JAMA study were in terrible health:

  • 20% had had a prior heat attack,
  • 18% had Congestive Heart Failure,
  • 55% had confirmed obstructive coronary artery disease by angiogram.

By contrast, in last years study, only 20% had heart disease of any kind (angina, heart attacks, or congestive heart failure).

To put it another way, its possible that the patients in this year’s study were “too far gone.” Testosterone is perhaps most beneficial as a preventative, and these men were well past the “preventive medicine” stage.

As one cardiologist put it:

“You need to be careful about the conclusion you draw from this JAMA study,” says Dr. Warren Levy, a cardiologist and director of Virginia Heart, based in Northern Virginia. “The study is of men who had undergone cardiac catheterization – so that already selects out a higher-risk population. The conclusion may be that for men with a higher risk of cardiovascular disease, testosterone therapy may increase risk slightly.”

But there is also another issue to be aware of:

Dr Anne Coppola, an associate professor of Endocrinology at University of Pennsylvania, wrote an editorial accompanying the JAMA study. This is right on the money:

Frustratingly little information is available in this VA database analysis about whether testosterone was appropriately prescribed according to accepted guidelines. In addition, 36% of the men were using testosterone injections, which have the disadvantage of nonphysiologic peak and trough levels when using either a once a week or once every two weeks dosing strategy.

I could not have said it better myself. This is why we have our testosterone replacement patients at PhysioAge use smaller doses twice a week, to get more physiologic levels. (And my more meticulous patients actually inject tiny doses three times a week, to get the smoothest levels possible.)

There is another advantage to dosing with small amounts more frequently: You don’t convert as much to estrogen. If you are getting testosterone replacement from a doctor that is advising you to use once-weekly testosterone injections plus an estrogen blocker, you need a new doctor. Blocking estrogen also has significant long term health risks, and with proper dosing, we very rarely need to do so in any of our patients.


Preventive Medicine is the name of the game. My practice is made up largely of pro-active, healthier patients, but I will certainly discuss this study with my few patients that may have significant health issues prior to walking in the door. With those people, we should proceed more cautiously. And with ALL patients, using physiologic dosing regimens is crucial.

This aricle originally appeared on 


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