TRT and Heart Attack Risk—Research Behind Claims Refuted
The rumor that Testosterone replacement Therapy (TRT) increases the risk of cardiovascular disease (CVD) events, which include heart attacks and strokes, continues to be repeated as though it were a fact.
If you’re concerned about a connection between TRT and heart attacks, 2 facts you need to know are:
- The 2 studies most often used to support claims of an increased risk have been heavily criticized under peer review
- The bulk of methodologically reliable research shows the opposite to be true—health risks increase with Low T
Flawed Research Connects TRT and Heart Attack Risk
TRT (Testosterone Replacement Therapy) has been falsely linked with an increased risk of cardiovascular disease (CVD) events that include heart attacks and strokes using unreliable data.
The first research project that caused concern was a large retrospective study published in the November 2013 Journal of the American Medical Association. Scientists claimed to have found an association between the use of TRT and increased adverse cardiovascular outcomes—the risk of mortality, heart attacks, or strokes—among male veterans.
8,709 men with low testosterone who were undergoing angiography were observed for an average of 840 days.
Of the 7,486 patients who did not receive TRT:
- 681 died
- 420 had a heart attack
- 486 suffered a stroke
Of the remaining 1,233 patients receiving TRT:
- Only 67 died
- 23 suffered a heart attack
- 33 had a stroke
These numbers seem to indicate that the group with testosterone levels normalized by TRT had a lower rate of cardiovascular issues. However, using an acrobatic statistical analysis that included more than 50 variables, the authors concluded that there was a greater risk with TRT.
Peers in the research community strongly criticized the project’s methodology:
- Some 1,132 patients were excluded because they were prescribed TRT after the event instead of being included in the untreated group, falsely increasing the events by 70%.
- Results from 104 women had been mistakenly included
- Inconsistent methods of TRT administration were used, even though the effectiveness varies between methods
- Varied durations of therapy
A second study by Finkle et al., published in September 2014 in the research journal PLOSONE, claimed to establish an association between TRT and cardiovascular disease by searching a large healthcare database for non-fatal heart attacks that followed an initial TRT prescription.
First, researchers looked for non-fatal coronary events in the 12 months before and 3 months after therapy was initiated—a major methodological weakness because the restorative or preventative cardiovascular benefits of TRT would take longer than this to appear. In fact, more reliable studies have excluded the first 3 months of treatment from their analyses entirely due to the possible effects of pre-existing conditions.
Peers, including Dr. Tamara L. Wexler, an endocrinologist specializing in reproductive and neuroendocrinology at Massachusetts General Hospital, also criticized the the exclusion of possible estradiol imbalances, which could increase the rate of mortality due to estrogen’s association with chronic heart failure:
“Exogenous testosterone not only raises the level of serum testosterone but also the level of serum estradiol. The failure of the authors to monitor and control estradiol levels is a serious defect in their research.”
(Her full comments can be read here.)
Despite poor methodological reliability and being discredited by peer review, these studies have been used as evidence against the safe use of TRT.
Sound Research: Heart Attack Risks Increase With Low T Levels
A comprehensive analysis of the current research conducted by Michael Kirby, Geoffrey Hackett, and Sudarshan Ramachandran, and published in Eur Cardiol, July 2019 concluded:
“The balance of evidence is that T therapy does not increase CV risk. Many studies have demonstrated that a low serum T concentration is associated with increased CV risk and mortality and that T therapy may have clinically relevant CV benefits.”
Specifically, they found evidence supporting the following conclusions:
- Higher endogenous testosterone levels reduced CV risk
- CV risk factors improved with TRT and
- Reduced mortality was observed in men who received TRT compared to untreated men
- Beyond 6 months, additional TRT health benefits appear, including stronger body composition and improved bone mineralisation
- Reductions metabolic syndrome risk, including improved BMI and waist circumference
- Improvements in glycaemic control and lipid profiles
The Mayo Clinic also disputed the assumed risk of heart attack with TRT while supporting the existence of TRT benefits:
“More recent studies show no increase in heart disease in men taking testosterone therapy. Some research even shows a lower risk of death in men receiving testosterone therapy compared with those not receiving therapy.”
Healthy Testosterone Levels—Learn the Benefits
Let’s set the record straight:
The bulk of reliable scientific research indicates that supplementary testosterone does not increase the risk of CV events (including heart attacks and strokes), and that there are numerous health benefits with normalized testosterone levels.
Testosterone Replacement Therapy (TRT) is the most effective way to restore and then maintain healthy testosterone levels for men who are chronically deficient.
Our comprehensive guide. It contains key facts and answers to the most common questions regarding the treatment of chronic low testosterone.
