A common concern with testosterone replacement therapy (TRT) is, "Does testosterone cause heart attacks?" Importantly, this worry has emerged from testosterone and estrogen blocker abuse, not medical TRT.
TRT is considered safe, and any misconceptions related to heart attack risks typically arise from misinformed associations rather than factual evidence.
These drugs are often abused by athletes and bodybuilders and used in such large quantities they can pose a risk. It's the same with many medications. If you take too much, it will be harmful. Unfortunately, this 'abuse and the media publicity behind it during the 80s and 90s has led to the assumption that TRT causes heart attacks.
Additionally, two prominent but poorly conducted studies state there is an increased risk of heart attacks and death from TRT. However, contrary to those studies, several studies over the last three decades show testosterone doesn't cause heart attacks. In fact, TRT decreases the risk of heart attack, stroke, and death.
Does Testosterone Cause Heart Attacks: The Flawed Studies
Study 1 Vigen et al
The two poorly conducted studies, Vigen et al. and Finkle et al., were what we call retrospective examinations. This type of study looks at historical insurance databases to see if people on a prescription for TRT developed any adverse outcomes. In this case, they were looking for heart attacks and mortality. The problem with these studies and what makes them unreliable is that they did not check to see if these men even took testosterone.
Just merely giving them a testosterone prescription does not mean they took the medication. Also, only the initial testosterone levels were examined and never in a laboratory over time. Therefore, we did not know whether they were even at therapeutic levels or even took testosterone. Neither of these studies holds any validity.
In another study that examined both of these studies, they stated:
"New concerns have been raised regarding cardiovascular (CV) risks with testosterone (T) therapy (TTh). These concerns are based primarily on two widely reported retrospective studies. However, methodological flaws and data errors invalidate both studies as credible evidence of risk. One showed reduced adverse events by half in T-treated men but reversed this result using an unproven statistical approach. The authors subsequently acknowledged serious data errors, including nearly 10% contamination of the dataset.
Study 2 Finkle et al
The second study mistakenly used the rate of testosterone prescriptions written by healthcare providers for men with recent heart attacks. They then used this number as a basis for their argument. These people had already had heart attacks, which had nothing to do with testosterone.
Many studies suggest testosterone is good for you with heart health benefits, including:
- Reduced heart attack rate in men at risk
- Improved Cardiovascular Health
- Reduced risk of death with higher levels of testosterone.
"Randomized controlled trials have demonstrated benefits of TTh in men with coronary artery disease and congestive heart failure. Improvement in CV risk factors such as fat mass and glycemic control have been repeatedly demonstrated in T-deficient men treated with T. The current evidence does not support the belief that TTh is associated with increased CV risk or CV mortality. On the contrary, a wealth of evidence accumulated over several decades suggests that low serum T levels are associated with increased risk and that higher endogenous T, as well as TTh itself, appear to be beneficial for CV mortality and risk."
Morgentaler A. Testosterone deficiency and cardiovascular mortality. Asian J Androl. 2015;17(1):26-31. doi:10.4103/1008-682X.143248
What Studies Show Cardiovascular Benefits when Taking Testosterone?
There are too many to present in this article. However, we will attempt to present the few that are most impactful.
First, endogenous testosterone levels and other hormones like estradiol are associated with heart disease risk in men. This study:
1. Endogenous Sex Hormones and Cardiovascular Disease in Men
This study showed that higher testosterone levels, estradiol, and adrenal hormones endogenously had a neutral or beneficial effect on heart attack risk. Meaning that if you naturally have low testosterone, you are more likely to have a heart attack. Conversely, it shows that if you have a naturally higher testosterone level, you are at a decreased risk for heart disease.
"Unlike women, men do not experience an abrupt reduction in endogenous sex hormone production. However, it has become clear that an age-associated decrease in the levels of (bioactive) sex hormones does occur. Whether endogenous sex hormones have an impact on cardiovascular disease has, for many years, remained largely unknown. Still, during the last decade, more attention has been drawn to the importance of testosterone, estrogens, and adrenal androgens in the etiology, prevention, and treatment of male cardiovascular disease."
"The purpose of this article is to summarize the evidence currently available on the association between endogenous sex hormones and cardiovascular disease in males. They reviewed published studies dealing with the relationship between circulating levels of sex hormones and cardiovascular disease in males. The studies reviewed in this article suggest that circulating endogenous sex hormones and estrogens have a neutral or beneficial effect on cardiovascular disease in men."
Muller M, van der Schouw YT, Thijssen JHH, Grobbee DE. Endogenous sex hormones and cardiovascular disease in men. The Journal of clinical endocrinology and metabolism. 2003;88(11):5076-5086.
Another study shows the same results:
2. The Unrecognized Cardiovascular Risk Factor.
This study looked at all the most recent studies showing that low testosterone puts people at risk of diseases and conditions related to metabolic syndrome. They also point out that men at risk of low T should be screened and have their levels returned to healthy levels to reduce risk factors.
"Normal levels of male sex hormones are essential to men's health. Many studies demonstrate that hypogonadal men are at higher risk for developing a host of metabolic derangements, including dyslipidemia, type 2 diabetes mellitus, obesity, and hypertension. We examined the most recent studies supporting this notion of hypogonadism as a cardiac risk factor by reviewing all relevant PubMed data. "
"Most studies showed an increase in metabolic disorders and cardiac events in hypogonadal men compared to their eugonadal counterparts. Mechanisms explaining this increased risk include adverse cytokine profiles produced by excess adipose (fatty) tissue, abnormal lipid metabolism by understimulated hormone-sensitive lipase, and abnormal cellular respiration leading to insulin resistance."
"In contrast, some studies have not demonstrated such an increased cardiac risk. Conflicting data between studies is expected, given the complexity of testosterone and its metabolic effects. Additionally, the interaction of testosterone with the androgen receptor differs based on an individual genome. Hypogonadism will affect individual men differently because of this genomic variance. The literature points toward true hypogonadism as a major cardiac risk factor. Men at risk of being hypogonadal should be screened and brought back to eugonadism with hormone replacement."
Potenza M, Shimshi M. Male hypogonadism: The unrecognized cardiovascular risk factor. Journal of clinical lipidology. 2008;2(2):71-78.
Testosterone is Good for the Heart
Now, what happens when you give testosterone to men? This process is complicated, but to simplify it, think about testosterone as being a gateway hormone. As you can see from the previous two studies, testosterone has benefits in protecting the heart by reducing the risk of metabolic syndrome and inflammation. Both of which increase the risk for cardiovascular disease.
Testosterone also reduces subcutaneous and visceral fat (around your organs) and fatty liver. So, what other benefits does testosterone have? Testosterone, although active, can be considered a prohormone - the precursor to the truly active hormones. So, what are the active hormones that come from testosterone? There are two - dihydrotestosterone (DHT) and estradiol.
DHEA Benefits the Heart
Dihydrotestosterone is the active form of testosterone. It is typically 10-100 times more active than testosterone. It gives you the same benefits as testosterone, such as reducing fat by increasing muscle, thus reducing the risk of inflammation and metabolic syndrome. All of this equates to a reduction in heart disease.
When it comes from testosterone, estradiol also protects the heart. Studies show that when you reduce estradiol via an aromatase inhibitor or fat, men have an increased risk of heart disease (up to 26%). One way estradiol helps reduce the risk of heart disease is by increasing good fatty acids. These are the cholesterol molecules you want because they help reverse plaque build-up and thus reduce heart disease.
As a caveat, there is an association of naturally elevated estradiol with heart disease in some studies. Why? Didn't I just tell you that it reduces the risk? Well, first, an association does not necessarily mean causation. Also, naturally high estradiol is not the same as giving testosterone to raise your estradiol. We need to understand the difference.
Estradiol, Testosterone, and Fat
Men who generally have naturally high estradiol are not all making it from testosterone. In fact, they make very little from their testosterone because these men typically have deficient testosterone. So, where are they making it from?
They are making it from fat. Fat produces estradiol via the action of an enzyme called aromatase. Fat in the cells generally causes an increased aromatase activity, which transforms the estrone in the fat to estradiol.
This increase in estradiol sends a signal to the brain, telling the body to reduce testosterone production because the brain thinks there is an excess of estradiol. Therefore, it must be coming from testosterone. The issue here is not the estradiol. It is the fat that produces it. Estradiol is not bad per se, but its effect on your testosterone is. You could say the estradiol is an eyewitness who happened to finger the innocent bystander (testosterone in this case) instead of the culprit (fat).
Therefore, we should block estradiol then by giving an aromatase inhibitor. No, because studies show that if you block estradiol, you will increase the risk for heart attacks, even though it will increase testosterone by stopping estradiol conversion. This is the reason steroid abusers use aromatase inhibitors, not because of gynecomastia or being over-emotional. You don't get either from estradiol.
Fat is the Issue
The issue here is the fat, not the estradiol. If you don't do something about the fat, it doesn't matter where the estradiol comes from. Fat kills. It causes heart disease. What about increasing testosterone by blocking estradiol? As a result, you can burn the fat with the muscle that testosterone produces. That would be okay if testosterone didn't depend on estradiol to sensitize your muscle to testosterone.
You need estradiol for your muscles to respond to testosterone. So, how do you reduce heart disease in men with a naturally high estradiol level from fat? You give estradiol in the form of testosterone. By doing so, you increase muscle and reduce fat, and, as a result, reduce estradiol from fat. As a result, you should never block estradiol because you put men at risk for heart disease. Testosterone, DHT, and estradiol all equally protect you against heart disease.
