Testosterone and Your Heart: What a Major New Study Really Found

[Nelson Vergel]

1.0 Introduction: The End of a Decade of Fear?​

For nearly a decade, a cloud of fear and controversy has hung over Testosterone Replacement Therapy (TRT). Fueled by a pair of widely publicized studies in 2013-2014, many patients and doctors became concerned about a potential link between testosterone treatment and an increased risk of heart attacks and strokes. This uncertainty led to regulatory warnings and left millions of men questioning the safety of a therapy intended to improve their health and quality of life.

In response, the FDA mandated a massive, long-term safety study to provide clear answers. That landmark study, called the TRAVERSE trial, was recently published, and its findings are reshaping our understanding of TRT and cardiovascular health. While the top-line results are profoundly reassuring for men on medically supervised therapy, the full story is more nuanced. The data reveals several surprising takeaways about the real risks and benefits of testosterone therapy.

2.0 Takeaway 1: The Big News - TRT Doesn't Increase Heart Attack or Stroke Risk​

The primary and most significant conclusion of the TRAVERSE trial is a direct refutation of the old fears. The study, which enrolled over 5,200 men who were already at high risk for cardiovascular problems, found no greater risk of major adverse cardiovascular events (MACE)—defined as heart attack, stroke, or death from cardiovascular causes—in men who received testosterone therapy compared to those who received a placebo.

This finding is a game-changer, as it directly addresses the concerns that prompted the FDA's 2015 safety warning. The strength of this conclusion has been so impactful that it has led to a major shift in the medical community's perspective. The Androgen Society, an international medical organization focused on testosterone, issued a definitive statement based on the TRAVERSE results and the weight of prior evidence.

It is the position of the Androgen Society that it has now been conclusively determined that TTh is not associated with increased risks of heart attack, stroke, or CV death.

For the influential Androgen Society, this data, combined with a mountain of prior evidence, marks the definitive end of a decade-long controversy. It provides the strongest evidence to date that when used correctly, TRT is not the cardiovascular threat it was once feared to be.

3.0 Takeaway 2: The Surprising Catch - A Rise in Heart Rhythm Issues​

While the news about fatal and catastrophic events was overwhelmingly positive, the TRAVERSE data revealed some noteworthy "red flags" in its secondary findings. A closer look at the results showed a statistically significant higher incidence of certain non-fatal heart issues in the men receiving testosterone.

Specifically, the study found:

• Heart Arrhythmias: A significantly higher rate of arrhythmias requiring intervention was seen in the TRT group (5.2%) compared to the placebo group (3.3%). This included 91 cases of atrial fibrillation (AFib), a common heart rhythm disorder, versus just 63 cases in the placebo group.
• Pulmonary Embolism: Researchers observed a doubling in cases of pulmonary embolism, a serious blood clot in the lungs, with 24 cases in the TRT group versus 12 in the placebo group. However, it is important to note this was not a primary or secondary endpoint the trial was originally designed to measure.

These findings create a more complex picture. This is particularly significant because it confirms, in a much larger and more rigorous study, similar safety signals that were raised over a decade ago in the smaller TOM Trial, which was halted early due to an increase in non-fatal cardiovascular events in the testosterone group. While TRT appears safe from the standpoint of heart attacks and strokes, it carries a measurable, increased risk of non-fatal heart rhythm disturbances and blood clots. This is a crucial consideration that cannot be overlooked, particularly for older men or those who already have pre-existing heart conditions.

4.0 Takeaway 3: The Dose Makes the Difference - Therapy vs. Abuse​

A critical point to understand is that the safety findings from the TRAVERSE trial apply only to medically supervised, therapeutic use. In the study, doctors carefully adjusted testosterone gel doses to maintain participants' hormone levels within the normal physiological range (specifically, 350–750 ng/dL). This is a world away from the supraphysiological (very high) doses of testosterone and other anabolic steroids often used without medical guidance by athletes or bodybuilders to enhance performance.

Using supraphysiological doses carries its own set of significant cardiovascular risks. Research shows that excessively high testosterone levels can harm the heart and vascular system by:

• Negatively altering lipid profiles (increasing "bad" LDL cholesterol and decreasing "good" HDL cholesterol).
• Activating chronic inflammation.
• Decreasing the availability of nitric oxide, a key molecule for blood vessel relaxation, and promoting vasoconstriction (the tightening of blood vessels).

A study using data from the National Health and Nutrition Examination Survey (NHANES) reinforces this point. While it found no link between high testosterone and death from heart attack or stroke, it did discover that testosterone levels greater than 1000 ng/dL were associated with a significant increase in all-cause mortality (death from any cause). This highlights a crucial principle: more is not better. The safety demonstrated in the TRAVERSE trial is contingent on proper medical management aimed at restoring normal, not excessive, hormone levels.

5.0 Takeaway 4: The Science Isn't Completely Settled​

The TRAVERSE trial was a monumental step forward, but experts are quick to point out that it didn't answer every question about TRT and long-term health. The scientific conversation is ongoing, and several key areas require further investigation before we have the complete picture.

Here are the most important unanswered questions that remain:

• Long-Term Safety: The average follow-up in the TRAVERSE trial was 33 months. This provides excellent short-to-medium-term data, but the effects of using TRT for decades remain unknown.
• Gels vs. Injections & The Role of Hematocrit: Most major trials, including TRAVERSE, used daily testosterone gels. However, injections are more common in real-world practice and are known to raise hematocrit (red blood cell concentration) more quickly. While there is data showing that a hematocrit level above the 52-54% threshold should not be surpassed due to a potential increase in the risk of blood clots, this critical link hasn't been rigorously investigated, nor has there been a large-scale safety trial directly comparing different TRT formulations.
• Personalized Medicine: People respond to hormones differently. Future research needs to explore how genetic factors, such as an individual's androgen receptor sensitivity, might influence how safe and effective TRT is for them. This could pave the way for a more personalized approach to treatment.

6.0 Conclusion: Navigating the New Landscape of TRT​

The landmark TRAVERSE trial has fundamentally changed the conversation around testosterone therapy. While groups like the Androgen Society now view the major safety questions as "settled science," the trial's secondary findings reveal that the story is one of evolving clinical nuance, not a closed book. The data provides powerful reassurance that TRT is much safer than previously feared regarding catastrophic events like heart attacks and strokes, but it also clarifies that TRT is not a risk-free therapy, revealing a clear association with non-fatal arrhythmias and pulmonary embolisms.

The key takeaway is that context is paramount. The safe use of testosterone depends on a proper diagnosis of hypogonadism, careful monitoring of potential risks like heart rhythm changes and hematocrit levels, and a commitment to maintaining hormone levels within a healthy, physiological range. As we move past the outdated fears, the new challenge is integrating this complex reality: How can patients and doctors best work together to harness the benefits of testosterone therapy while carefully managing its newly clarified risks?

References​

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[Nelson Vergel]

More on heart palpitations and AFIB on Androgel: Heart Palpitations and AFIB in Older Men on Testosterone: Signals from TRAVERSE - Excel Male Health Forum