Testosterone Replacement Therapy and Cardiovascular Disease

Does Testosterone Replacement Therapy (TRT) cause Cardiovascular Disease, Stroke, or Heart Attacks?

The Idea doing TRT is Dangerous Continues to Trump Science.

Many male patients come into the clinic with the impression TRT is dangerous because it causes cardiovascular disease, strokes, and heart attacks because their doctor told them so.  Even if their testosterone level is below normal and they have symptoms of low testosterone, they are told not to use TRT.  Never has any proof supporting these statements been offered to substantiate the doctors claim.  Only fear has been established in an unknowing and questioning patient.  Why?

The conventional medical establishment erroneously continues to conclude TRT increases the risk of cardiovascular disease, stroke, heart attack and prostate cancer. Discussed in a previous blog post, Harvard-based MD, Abraham Morgentaler, has demonstrated all these theories to be mistaken in numerous publications.

This blog post will look into the November 2013 study published in the well-respected Journal of the American Medical Association (JAMA), entitled “Association of Testosterone Therapy with Mortality, Myocardial Infarction, and Stroke in Men with Low Testosterone Levels.”   This is the study the conventional medical establishment uses to prove men should not do TRT.  However, this study makes an incorrect conclusion based on flawed data, and yet can still be found in JAMA in its entirety for all to read again and again.  The publication, although deemed no longer credible by experts, is still believed by the general medical community.  Why?

Hormone and Testosterone Replacement Therapy Called Dangerous in the Media

The 2013 study was the first to report a negative association and outcome with testosterone therapy.  This bad news rapidly made its way throughout the world on major media platforms causing a frenzy.  Soon after the article’s release, medical groups followed suit and declared extreme caution regarding testosterone therapy. The results of this study were accepted as definitive and testosterone therapy was deemed dangerous.

One such high-profile editorial from the New York Times was published entitled “Overselling Testosterone, Dangerously,”.  The editorial contends testosterone prescriptions have increased in recent years simply due to the fact that men cannot handle getting older. The author states there is reckless overprescribing and overselling of hormone replacement therapy and cites the majorly flawed November 2013 study and the Women’s Health Initiative to back this stance. Hence, we have two flawed studies still being cited by doctors today.

A Look into the Study

The November 2013 study priming fear surrounding testosterone therapy was a retrospective analysis of 8709 men in the Veterans Administration healthcare system with serum testosterone levels below 300 ng/dL who had undergone coronary angiography. The rates of strokes, heart attacks and deaths were calculated and compared between men receiving testosterone replacement therapy (TRT) and men not receiving testosterone.

The authors concluded the absolute rate of events among men receiving TRT was 25.7% compared to 19.9% for men in the untreated group.

However, Morgentaler’s research into the study revealed this conclusion to be misleading and incorrect. Why?

• The authors referred to their statistics as absolute rates however absolute rates refer to raw data. The authors adjusted the percentages using complex statistics to account for 54 variables so the resulting conclusion was not based on raw data.
• The authors excluded a group of 1132 men and reported they only excluded 128 men. This is an error rate of 89%.
• 1 out of 11 “men” were actually women. Months after publication, 100 women were identified among the original subject group of 1132 individuals.

The most eye-opening error was when the actual raw data percentages were analyzed in this study, an opposite conclusion was found.

• The percentage of men who suffered a cardiovascular/stroke event was half as great in the TRT group than the untreated group: 10.1% for the TRT group and 21.2% for the untreated group showing TRT decreased the incidence of cardiovascular/stroke events.

Two corrections were made by the authors within months of publication. They corrected for the misuse of the term “absolute rate of events” by replacing it with “Kaplan-Meier estimated cumulative percentages with events,” producing a more accurate reflection of the statistical nature of the results and conclusion.

After multiple letters were submitted to JAMA pointing out the flaws of the study and the incorrect conclusion, the authors replied they had made an incorrect notation and made an additional correction. Medical experts around the world concluded these errors rendered the results no longer credible.

Retraction of Testosterone Study Demanded by World Experts

On March 25, 2014, a letter was submitted to the JAMA Editor-in-Chief recommending a retraction of this publication as it was no longer credible. Subsequently, the world’s experts in men’s health and testosterone therapy submitted a petition for the retraction, marking the first time in history distinguished researchers and clinicians worldwide united to demand the removal of a study.

The petition for retraction of the article was signed by “20 medical societies and more than 150 of the most distinguished medical scholars, researchers, and clinicians from 28 countries, including 8 emeritus professors, 9 journal editors, and 14 society presidents. The only continent not represented was Antarctica. ISSAM and several regional Aging Male societies were signers.”  The controversy was not reported by the media.  Why?

Testosterone Therapy and Cardiovascular Risk

Morgentaler et al. published an article, in light of the November 2013 study, reviewing the literature of testosterone therapy and cardiovascular risk in publications between 1940 and August 2014.  Only four articles were found to suggest an increased cardiovascular risk with testosterone prescriptions. A further analysis of these four articles showed they had serious methodological limitations, questionable studies and events. These four articles are in comparison to “several dozen studies that have reported a beneficial effect on normal T levels on cardiovascular risks and mortality.”

In conclusion, Morgantaler et al. stated,

• “There is no convincing evidence of increased Cardiovascular risks with TRT.
• On the contrary, there appears to be a strong beneficial relationship between normal T levels and Cardiovascular health that has not yet been widely appreciated.”

Integrity of Medical Literature, The Media, and Patient Well-being

Extensive literature spanning decades has repeatedly shown TRT to improve risk factors for chronic diseases and outcomes.  Unfortunately, a weak study or two can quickly disseminate in the media and fear suddenly trumps science resulting in a remarkable negative impact on medical practices and patient well-being for decades.

Morgentaler stated, “Lost in the media frenzy that followed this article’s publication is the fact substantial evidence accumulated over 30 years has shown repeatedly higher testosterone levels are associated with better cardiovascular outcomes. In the interests of medical science and the public good, JAMA should do the right thing and retract the article.”

The article was not retracted and remains in JAMA today. In a time of doctors being silenced for “misinformation,” JAMA is complicit in the misinformation of this article. Clinicians continue to cite this flawed study to support opposition to testosterone therapy jeopardizing the health and well-being of patients and perpetuating the fear surrounding hormone therapy.

The requested retraction of this article by clinicians and medical societies around the world is unprecedented, producing a cautionary tale of how it can take decades to correct a flawed established medical “truth”, during which time,  patients continue to suffer.

Have an awesome day!  Dr D