When I tell men over 50 that I’m on Testosterone Replacement Therapy (TRT) they often ask if TRT causes heart attacks. “I hear things,” they say, in their Tony Soprano voice. “I hear it causes, ya know, heart problems. I got enough problems.”
The short response is that TRT does not (necessarily) cause heart problems. In fact, in most cases, therapeutic levels of serum (in the blood) testosterone can be cardio-protective.
When we discuss heart problems with our average New Jersey man, what we are really discussing is ASCVD or atherosclerotic cardiovascular disease. Included in this suitcase term are angina (pain in the heart not caused by a woman whose name ends in the ah sound), Myocardial Infarction (MCI), a heart attack, as well as an array of heart-related events known under the acronym, MACE, which stands for Major Adverse Cardiac Event. The question is this. Does being on TRT, a phrase I’ll define in a moment, cause MACEs or can it accelerate Tony’s rapidly descending pathway to such events?
The truth is, it's more likely his salami-based diet and gym-avoidant lifestyle that are causal factors rather than the TRT he is considering.
Let’s first look at the problems associated with low testosterone, which is why one would consider TRT. In this report published in the National Library of Medicine, the authors explain that low testosterone is associated with endothelial dysfunction. The endothelial is the inner lining of the artery walls. When it is dysfunctional, a couple of things can occur. For one, a damaged endothelial wall, or the lesions that are produced by among other factors, high blood pressure, can be sticking points for the lipoproteins (specifically LDL and ApoB) which transport cholesterol through the bloodstream. The lipoprotein particles stick to the lesions and begin to aggregate in the area, forming soft plaque, which can break free and block arteries in the heart or brain causing heart attacks or strokes. There is yet another process that creates the plaque, but I’ll spare you that level of granularity for now.
A damaged endothelial wall can create a situation in which the body reads the damaged lining as a tear and sends clotting agents to repair it, adding to the plaque that has likely, thanks to your genes, been forming in your artery walls for decades. It’s the body’s own inflammatory response that exacerbates the plaque problem. Next, what I would call the calcium paradox begins to take effect. In most people, after plaque accumulates, a layer of calcium forms over the top of it, doing two things. It creates a hard cap on the soft plaque, reducing the chances that the plaque can break off and create a clot, causing a heart attack. The problem is the calcium adds an extra layer within the artery that further shrinks the lumen, the inside space in the blood vessel, further limiting blood flow.
Your calcium score is measured with a non-invasive cardiac CT scan. A word of caution. Any calcium score above zero means you have plaque, but a zero score does not mean you don’t have plaque. It simply means the body has yet to form the calcium layer over the soft plaque that may exist. To be clear, a zero is almost always better than a number above zero, but it doesn’t tell the whole story.
In addition, the endothelium, the cells of the endothelial wall, produce nitric oxide (NO), which helps to relax the artery walls so they can expand and contract for proper blood flow. Like muscles, when they don’t move, they become stiff. Your arteries are much more like muscles than pipes. Before research scientists discovered that the endothelium produced the NO molecule, that ‘gas’ was known as endothelial-derived relaxation factor.
Does it mean that low T per se is the cause of endothelial dysfunction? Maybe not. To be fair that’s a little like saying that if you took an aspirin and it fixed your headache that the pain was caused by a lack of aspirin. However, as we will see, there are a number of poor health indicators and blood markers that exist in the presence of low testosterone.
Let’s back up.
What exactly is TRT? To begin with, we’re animals, primates really and as such, our mission on earth is to produce offspring. Testosterone works with FSH or follicle stimulating hormone, to produce sperm. Testosterone also plays a role in libido, the sex drive that pushes us to mate with the aforementioned woman whose name ends in ah, or nearly any other womb-endowed member of our species, despite her lack of interest in our deadlift PR’s.
As we age and our relevance in creating progeny declines, we begin to produce less and less testosterone. It’s a grim reality of the natural aging process, along with repeating ourselves and ear hair. Sidebar: it isn’t dying that scares us so much as irrelevance. We’ll talk about that at another, more depressing time.
There are a host of other age-related declines not limited to cognitive speed, foot speed, loss of muscle/energy and other outward symptoms. Some of these declines can be mitigated or offset through diet and exercise, with the latter being paramount. Much of this natural loss of function is associated with low testosterone, a sex hormone that can be increased with fat loss, better sleep and exercise. Increasing testosterone is beneficial in several ways, including the enhancing of our ability to work out harder and recover faster so that we may continue to work hard to maintain and yes, increase muscle mass along with increasing bone density. Thicker bones are harder to break. In people over 80, a broken hip or femur is tantamount to a death sentence.
Over the last 5-10 years, medical science has come to recognize that strength is an important marker of longevity. Therapeutic levels of testosterone help us to age better, to be stronger, more agile, viral and productive, well after the age at which our culture tends to write us off. Exercise, by the way, is also critical for staving off neurodegenerative diseases and yes, we will explore how in upcoming articles.
Testosterone Deficiency (TD) is measured in two ways: bloodwork and clinically, that is, by presenting symptoms to your doctor. The “normal” range of serum testosterone is between 300 and 1,000 nanograms per deciliter, depicted on your results as, for example 450 ng/dl. But what is normal for one man may not be for another, which is why symptoms, such as low libido, lack of energy, loss of muscle mass, and decreased sexual function, should be factored in with your bloodwork for your doctor to determine if you are a candidate for TRT and for your health insurance to determine if they’ll pay for it.
Exogenous (from outside the body) testosterone is administered through a few mechanisms, the most common of which are gels and intramuscular injections. The gels are ok but don’t increase your T levels by much. If your bloodwork shows your testosterone levels are hovering around the low normal, say 300 ng/dl, you can expect your levels to go up to around 400 on the gel but not much more.
The better option is intramuscular injections, in the thighs, butt or shoulders, but a lot of guys don’t like to give themselves weekly shots. Happy Mother’s Day to those guys. The alternative is for the doctor, or some other health professional, such as a PA or nurse, to give you the shot, and a lollipop. They usually give the shots twice a month for the sake of convenience. The problem with that method is that you end up getting a big surge of testosterone for your body to deal with, followed by two weeks of decreasing levels. Weekly or even twice weekly shots self-administered give your body a smaller, steady push of T which is better for the body overall because it better mimics the natural phasic expression of the hormone.
How much testosterone? Typical doses are between 100 to 200 milligrams per week, but most seem to be more in the 100mg range. I’m on 100-125mg per week depending on my bloodwork, which I get done quarterly. My bloodwork is a relatively complete panel, measuring metabolism, my lipid profile, vitamin levels, PSA and testosterone. My T levels are typically in the high 800s to low 900s, ng/dl.
Back to the original question, does TRT increase the risk of a major cardiac event?
In the 2022 study cited above the authors noted the following. “On 17 September 2014, the U.S. FDA convened an advisory committee to review the use of TRT and its cardiovascular risks. The committee was asked to give an opinion on the current indications for TRT and whether manufacturers of testosterone products should conduct studies to assess cardiovascular risks associated with the use of TRT. The committee concluded that there was not enough evidence that TRT was a significant CV risk for any given group of patients treated with TRT.” In simple terms, the FDA concluded there wasn’t even enough evidence of risk to warrant a closer look.
A 2017 study published in the Debakey Cardiovascular Journal stated, read this carefully, “[However], there currently is no credible evidence that T therapy increases CV risk and substantial evidence that it does not. In fact, existing data suggests that T therapy may offer CV benefits to men.”
That same study highlighted the litany of diseases that are linked to testosterone deficiency. “Low T levels are also associated with chronic medical conditions such as metabolic syndrome, diabetes, dyslipidemia, hypertension, renal failure, frailty, malignancy, and cardiovascular (CV) events. Several meta-analyses and systematic reviews have clearly associated TD with increased CV disease and mortality.”
I’ll step into the metabolic health arena in an upcoming article because I believe there’s enough evidence offered by medical doctors and PhD researchers that strongly suggest a laser focus on LDL may be insufficient to slow, halt or even reverse CVD.
“But I hear it thickens the blood,” said the gym bro.
Yes, there is some evidence that TRT can increase thrombotic events, also known as blood clots. In some individuals, the body reacts to endogenous testosterone by increasing the number of red blood cells, which means more blood volume and thus elevated blood pressure. Anyone on TRT should be getting regular bloodwork which includes a check of their blood pressure. For those rare individuals who respond to TRT in this manner, regular, perhaps quarterly blood donations will usually fix the problem. If you’re reluctant, know that your blood donations benefit society so there’s plus.
There are some studies that raise a concern for risk of cardiac events, particularly in people with existing CVD. The literature seems to suggest that cardiac events are likely to happen within the first 90 days of use, but again that data are confounded by who was studied, the ages of the cohorts, their fitness levels, the degree to which they were hypogonadal, other meds they were on and many other covariants. When older populations are studied, the confounders have to be more carefully considered.
However, the DeBakey article stated, “Three recent randomized, placebo-controlled trials demonstrated that administration of T improves myocardial ischemia in men with CAD. All three found that in men with CAD, testosterone prolongs the time to exercise-induced ST-segment depression as measured on treadmill stress testing.24–26 Testosterone has been reported to have direct vasodilatory effects on coronary arteries in men with CAD.” #Stamina
One more. This 2023 study published in the New England Journal of Medicine demonstrated that in a “multicenter, randomized, double-blind, placebo-controlled, noninferiority trial,” there was no difference in cardiac events between the group administered testosterone and the placebo group after a three-year follow-up. 5,246 men were studied. There were 190 events in the T group and 193 in the placebo group.
From what I’ve learned, I believe the potential benefits far outweigh the risks, but I’m not risk-averse. The benefits include increased energy, muscle mass, libido, sexual function and insulin sensitivity. All these factors lead to a general upswing in mood and well-being, particularly if you exercise and get proper sleep.
It appears clear that low T causes more misery and early death than therapeutic levels do. What is also clear is that you should get your diet, sleep and exercise houses in order before you turn to pharmacological interventions. This concept applies in many areas beyond TRT, including Type II diabetes and back pain.
I recommend this article as a starting point only. It’s far from all-encompassing. There’s a lot to learn. Get after it.
If all of this sounds too burdensome, I suppose I understand, to a degree, or not.
Actually no. If you want to live a robust life and have a longer, stronger health-span and not just a longer lifespan, you must take control and make some changes. You must know your numbers: BP, lipid levels, kidney/liver function, fasting glucose levels, VO2 max. Can you deadlift your own body weight? Can you hang from a bar for ninety seconds? You need to stay lean and exercise. No love, sauntering through the mall with a bag of donut holes isn’t exercise. Start walking briskly before running, add resistance work. Make slow, incremental but continuous progress. Focus on making healthier food choices and getting stronger. Get a check-up and bloodwork before you make drastic changes.
Getting started is hard; dying young is harder.