Headline: Testosterone Doubles the Incidence of Heart Attack (2014)  Reality: Testosterone Group had 0.7% more Heart Attacks

A paper by Finkle et. al. (Increased Risk of Non-Fatal Myocardial Infarction [Heart Attack] Following Testosterone Therapy Prescription in Men) published in the free-access journal PLOS One examined insurance records of 225,000 men aged 50 to 75 and concluded that the risk of non-fatal myocardial infarction increased during the first 90 days of testosterone therapy, and even more so when the patient had a prior history of cardiovascular disease.  The report of “doubled risk” made every news television show and newspaper, but the actual increase was 7 cases per thousand patients.

 

The anti-pharmaceutical campaign trumpeted the findings, and the anti-aging crowd attacked the study for its limitations (which are discussed in the paper). The Food and Drug Administration reviewed the results and concluded that patients should not stop testosterone without consulting their physician.

 

For comparison, in 2012 another retrospective study was published about aspirin “doubling” the risk of gastrointestinal bleeding. The absolute increase in bleeding from one group to another was 0.19%. The FDA made a similar “not stop” statement about the aspirin study as they did in the testosterone study. I am unaware of any cardiologist who recommended a discontinuation of the drug.

 

Relative risk, the statistic used in the Finkle study, can be 100% greater if for example; a group of one million patients had two cases of something and the comparison group of one million had only one case. It is a valid statistical method for detecting possible relationships, but it can be misleading. When Medicare first published surgical outcome data, Massachusetts General Hospital had relatively poor outcomes; when the data was corrected to account for the complexity of the surgical cases, Massachusetts General had excellent outcomes. The same data can give different conclusions. A quote comes to mind (whose origin is contested between Mark Twain or Benjamin Disraeli), “There are three kinds of lies: lies, damned lies, and statistics.”

 

The Finkle study does indeed demonstrate an increased risk of heart attack during the first 90 days after filling a testosterone prescription. However, some details are missing. It does not show if patients took the prescription, or had blood levels checked before and/or after the prescription. Since the symptoms of low testosterone can resemble depression and/or hypothyroidism, the possibility holds that inadequate evaluations can lead to inappropriate outcomes.

 

Testosterone is enormously beneficial when prescribed in the right dose and for the right reasons:

 

Testosterone administration increases coronary artery diameter and flow, improves symptoms in men with chronic stable angina, and reduces peripheral vascular resistance in chronic heart failure. Animal studies have consistently demonstrated that testosterone is atheroprotective, whereas testosterone deficiency promotes the early stages of atherogenesis.”  (Kelly and Jones – Journal of Endocrinology – 2013)

 

All medications have risks. The short term risk of testosterone increasing the odds of blood clotting has been known for 50 years, so why the recent alarm? Perhaps because the number of testosterone prescriptions has skyrocketed to over one million per year since the “Low-T” campaign began. This creates the possibility that some doctors who don’t appreciate the risks are being pressured to prescribe testosterone. Finkle only found the increased risk in the first 90 days (short term) and no increased risk thereafter.  Kelly and Jones are describing the long-term benefits of testosterone. The correct conclusion is that there might be more short-term risks involved, but that there is a continuously growing understanding of the long-term benefits.

 

The study’s greatest flaw is the choice of the groups that were used for comparison. Finkle had access to almost unlimited data (he actually owns the company that supplied the data), but he chose his groups based on one group receiving prescriptions for testosterone with the other group receiving Viagra type drugs. Why didn’t he choose two groups of men with existing heart disease of equal severity, one who received testosterone prescriptions and one who didn’t?

 

If this was the case, he could have identified the characteristics of the men having the heart attacks in order to help physicians screen them out before treatment, or pursue alternatives. It would have been extremely helpful, for example, to know which men were treated according to the Endocrine Society Guidelines, and if following the Guidelines reduced the risk. As circumspect clinicians, Dr. Nadelberg and I have reviewed our protocols (based on the Guidelines) and they still reflect adequate caution.

 

The other unanswered question is whether the heart attacks in the first 90 days were due to testosterone or was it the natural course of their underlying heart disease? Two groups of equal cardiac severity would have answered this question too.

 

This study leaves us with an increased concern about why these patients were treated the way they were, and until there is a study produced using sounder methodology, we won’t get much else. This is another lost opportunity.

James Katz MD

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