Does low testosterone lead to heart disease?

Is low testosterone a contributor to cardiovascular disease? Is testosterone replacement the answer? It's a bit more complicated than that, according to researcher Ben Trumble, whose study of the Tsimane, an Indigenous population in the Bolivian Amazon, upends previous assumptions about low testosterone.

Trumble, an associate professor in Arizona State University’s School of Human Evolution and Social Change and the Center for Evolution and Medicine, addressed those questions his paper, “Testosterone is positively associated with coronary artery calcium in a low cardiovascular disease risk population,” published by the peer-reviewed journal Evolution, Medicine & Public Health.

Trumble also recently had a paper, titled “Energetic costs of testosterone in two subsistence populations,” published by the American Journal of Human Biology.

ASU News talked with Trumble about the studies and their findings.

Editor's note: This interview has been edited for length and clarity.

Question: How are testosterone levels linked to heart disease?

Answer: There have been a number of observational studies that have reported that men who have low testosterone have higher morbidity and mortality. Men with low testosterone are more likely to have a number of health conditions, including cardiovascular disease. Men (in the lowest 10th percentile) of testosterone levels have the highest risk of dying within five years.

So, in the United States, a lot of doctors have started to look at that association and say, “Maybe there’s something about testosterone that’s protective, and that if we give guys testosterone, we could prevent this morbidity and mortality.” That’s led to this huge rise in the number of men taking testosterone replacement therapy.

Q: Is that a potential solution to limiting the risk factor of heart disease?

A: One of the problems with that idea is that testosterone is the canary in the coal mine. It is downregulated as soon as guys get sick. So, guys who have low testosterone, it’s not that the testosterone is causing whatever their illness is. It’s just a symptom of whatever illnesses they do have.

In fact, giving guys testosterone in that case might actually not be the best thing to do because then you’re adding something back that has a bunch of energetic costs associated with it. If it’s being downregulated on purpose, then by taking testosterone you might be fighting against your own physiology.

Q: Your paper says cardiovascular disease is a special case when it comes to testosterone levels. Why is that?

A: Anytime testosterone interacts with fat tissue, it converts to estrogen. Estrogen and testosterone are chemically almost identical, and the male brain doesn’t differentiate well between the two hormones. So if I injected myself with a bunch of estrogen right now, my brain would say, “Whoa, we have way too much testosterone. We need to slow down our testosterone production.” When guys put on body fat, testosterone interacts with the fat tissue and converts into estrogen, and the brain says, “We’ve still got enough testosterone.” So you start producing less and less testosterone, and you start getting a higher estrogen-to-testosterone ratio. And that actually makes it easier to put on more body fat.

So this is where it becomes important in terms of cardiovascular disease. If guys are obese, they’re going to have low testosterone because their testosterone is converting to estrogen. So if you look at the association between testosterone and cardiovascular disease, you might note that guys who have low testosterone tend to have higher rates of cardiovascular disease, but it’s really obesity that is resulting in both cardiovascular disease and low testosterone.

Q: You’re hesitant about testosterone replacement. Why?

A: Low testosterone is usually a symptom of a bigger problem. Our bodies downgrade testosterone when we have to focus on health issues, so by taking supplemental testosterone, we are circumventing our own bodies. Plus, there haven't been very many large, long-term randomized controlled trials, so we may not know all the risks yet.

A paper that came out in 2018 suggested that 40% of guys that were prescribed testosterone never had a testosterone test before they got prescribed. Also, there aren’t many good studies looking at testosterone replacement therapy and cardiovascular disease. It’s difficult to assess the real association because you can’t really disentangle testosterone, obesity and cardiovascular disease.

Q: You’ve worked with the Tsimane — Indigenous people in lowland Bolivia — for years. How does their lifestyle influence your paper?

A: Unlike the U.S., where low testosterone is associated with cardiovascular disease, we found that Tsimane men who have higher levels of testosterone were more likely to have cardiovascular disease.

Q: That sounds counterintuitive.

A: What it suggests is that perhaps testosterone isn’t that great for the heart, and having higher levels of testosterone isn’t going to prevent cardiovascular disease at all. This population is very physically active and has low levels of cardiovascular disease. Our study suggests that the focus should be on reducing obesity and other cardiovascular risk factors and not on low testosterone.

In the U.S., many older men have high levels of body fat, which makes it hard to test the association between testosterone and cardiovascular disease. So working with a population like the Tsimane is kind of ideal because they have low body fat, and thus we can examine associations between testosterone and cardiovascular disease without obesity confounding the situation. If Tsimane want meat for dinner, they have to go hunting, and the average hunt is about 8½ hours and covers a little over 10 miles. So, we can look at the association between testosterone and cardiovascular disease without this confounding factor of obesity.

Q: This is hard to grasp because there seem to be mixed messages. A higher testosterone level in the Tsimane is associated cardiovascular disease, but it appears to be the opposite for people in the U.S.

A: Yeah, when it comes to cardiovascular disease, everybody wants a silver bullet. Like, do this one simple thing and everything will be fine. Unfortunately, that silver bullet probably isn't going to be testosterone. It’s also not going to be just about diet. It's going to be a complicated interaction between both diet and physical activity, and immune function is going to play an important role as well. We’d love to have a silver bullet to prevent or fix cardiovascular disease, but unfortunately it is not going to be that simple.