Testosterone therapy for older men has skyrocketed in popularity. If you’re reading this article, chances are you’ve considered it or know someone who has. And the chances are also good that you’re aware of some of the controversy surrounding it. There have been sharp disagreements about its benefits and risks and who should be using it.
By the end of this article, you'll have the insights you need to make an informed decision about testosterone therapy. We’re going to look at the fascinating history of testosterone treatment, see what the best science says right now, and talk about a controversy around a new study that could change how we move forward.
Table of Contents
1. History
4. Takeaways
5. References
Section 1: History
We’ve actually had some idea about the effects of testosterone for a very long time. People knew the testes produced something that had a big impact on behavior. In the ancient world, castration was sometimes used to make slaves more passive and obedient. Incredibly, it was also used to keep males from going through puberty to preserve their singing voice.
Noticing these effects, people from Roman times tried eating animal testes to increase their energy and sexual function. French scientist Charles E. Brown-Séquard tried out a more sophisticated version of this approach in the late 1800s. He gave himself daily injections of a mixture he took from animal testes and claimed to see dramatic results—reporting he regained strength and increased energy.
But we know now this could only have been a placebo effect. That crude approach couldn’t actually work. They were on the right track, but our understanding had a long way to go. In particular, we needed to know what it was in the testes that explained their effect on the body.
We started to make real progress in the 1800s. A German scientist, Arnold Adolph Berthold, conducted a novel experiment. He castrated several roosters and then transplanted testes into some of them and compared their behavior. He noticed those who got the transplants had normal male rooster behaviors restored. The others didn’t. His conclusion about what was going on was remarkable for the time. He theorized the testes were producing something that traveled through the blood and affected the whole body—in other words, what we would now call a hormone.
In the early 1900s, researchers figured out more about hormones and how they work in the body. They began to be able to identify and isolate them chemically. Big breakthroughs came in the 1930s. Scientists finally identified the crucial hormone made by testes and named it “testosterone.” In the same decade, they figured out how to synthesize testosterone in the lab.
Now the question was: Can we use this testosterone to treat men whose levels are low? And if so, how? This turned out to be harder than we expected.
It was found that taking testosterone orally didn’t work. It was broken down by the liver and didn’t wind up in the blood. A different form was developed that seemed effective when taken orally, but it was later found to have toxic effects on the liver.
Testosterone was also given in injections. Those seemed to work better. But until the 1970s, we didn’t have a good way to measure testosterone levels in the blood. We were aiming for a target of “normal,” but couldn’t tell if we hit it.
Once new testing methods became available, we had a bit of a shock. All of the methods of testosterone delivery then in use made levels too high or too low. We needed something better.
That came in the 1990s with a patch applied to the skin. This finally gave us a way to reliably achieve normal testosterone levels. There are several other reliable methods in use today, including gels and injections.
This was a really exciting development. We were at a point where we could accurately assess testosterone levels and help raise them in men when they were low.
But we quickly found ourselves with two problems. First, testosterone treatment surged in popularity. Health influencers began to tout its benefits for improving strength, energy, and sexual function. Men started using it even when their testosterone levels weren’t clinically low.
Second, new data emerged that testosterone therapy could have dangerous adverse effects.
Section 2: The Present Consensus
Where does that leave us now? Let’s look at what the clinical guidelines tell us about who should consider testosterone therapy and what the true risks are. Then we’ll examine the new study and the controversy it’s causing in the field.
1. Who Is an Appropriate Candidate?
Current guidelines rest on three important considerations. First, we know unusually low testosterone levels can have negative effects. The first to show up are decreased energy, a weaker sex drive, and a depressed mood [1]. If low testosterone levels persist for years, this can also lead to decreases in muscle mass and body hair [2]. And we also know that testosterone therapy can counteract some of these problems.
Studies have found it can improve libido and sexual function [3]. Therapy can also improve muscle mass and strength. In one study, 10 weeks of therapy increased fat-free mass, muscle volume, and the maximum weight participants could lift [4]. And testosterone therapy can improve bone density. A long-term study found it could increase and then maintain bone density in men who had low testosterone before treatment [5].
What about mood? In a large study of testosterone therapy in older men, participants reported better mood and milder depressive symptoms compared to the control group [6].
Overall, this much is clear: low testosterone can cause problems, and if a person has symptoms of low testosterone, therapy can help correct them. That’s the first important consideration that underlies current guidelines.
2. What If Testosterone Levels Aren’t Abnormally Low?
The second consideration is this: we don’t have good evidence about the benefits of testosterone therapy for those whose levels aren’t abnormally low. And I will go through the controversial study shortly.
Now, the word “abnormal” is important. As we age, testosterone levels naturally fall [7]. This means an older man will have testosterone levels significantly lower than a young man. But this doesn’t mean his levels are low in a clinical sense. In other words, the testosterone levels may not fall to a threshold where major issues occur.
In contrast, clinically low testosterone levels that cause symptoms are usually due to problems with the testes or the region of the brain that controls testosterone production.
As more people know testosterone declines with age and affects things like sexual function, lots of men whose levels aren’t abnormally low are trying therapy. Prescription sales of testosterone ballooned from $100 million in 2000 to about $2.7 billion already by 2013, and it’s only gone up from there [8]. But most of the research so far has been done in men with genuinely low testosterone and with symptoms. Can therapy benefit those who are simply experiencing the normal decline due to aging? At this point, we simply don’t have the data to say.
And you might think, “Well, even if it does nothing, it might help. So why not try?” But this is where the third consideration comes in. There are risks associated with testosterone therapy.
3. Risks of Testosterone Therapy
For example, one study found testosterone therapy is linked to an increase in plaque in the arteries [9]. Testosterone therapy can also raise red blood cell counts. This condition is called erythrocytosis and is the most common adverse effect of therapy [10]. The concern is that this could lead to higher blood pressure, blood clots, and heart attacks [11]. So far, data on those using testosterone therapy correctly don’t clearly show a higher risk of these problems. But the evidence is mixed and inconclusive. It has led both the Endocrine Society and the FDA to issue warnings about the potential cardiovascular risks of therapy [12].
Taking these three considerations together, clinical guidelines recommend testosterone therapy only for those who have clinically low levels along with symptoms of low levels [13]. The reasoning is that this balances our confidence in benefits with our awareness of risks. The guidelines recommend against older men taking testosterone who don’t have symptoms or whose levels aren’t low. In these cases, there are known risks and unclear benefits [14].
Section 3: The Controversy
A new study has caused a lot of controversy. Its results seem to require a big adjustment in the logic we’ve just looked at.
The study was called the TRAVERSE trial [15]. It centers on the question of cardiovascular risk. It involved over 5,000 middle-aged to older men with pre-existing heart disease or a high risk for it. These men also met the normal conditions for testosterone therapy: they had clinically low testosterone and symptoms of deficiency. After around two years of treatment, researchers followed up for another three years. They were looking for symptoms of heart problems including heart attacks and strokes.
Here’s what they found. Seven percent of the patients taking testosterone had heart attacks or strokes during the study, which sounds very high. But the figure for the placebo group was 7.3%. The researchers concluded that testosterone-replacement therapy was no worse than placebo when it comes to causing heart problems [15].
At first glance, it looks like this study has important implications. If there isn’t actually an increased risk of heart problems with testosterone therapy, then we don’t have to be as cautious about prescribing it. Maybe more men could then try it, even if the benefits at this point are unclear.
But does the study really show heart disease risks are overblown?
That’s certainly how some are interpreting it. Experts at a recent conference on testosterone treatment claimed this study “can finally put to rest the anecdotal and wholly unproven fear physicians have that testosterone therapy will cause heart disease.” But let’s take a closer look.
4. A Closer Look at the TRAVERSE Trial
Yes, the percentage of patients who experienced heart problems was slightly lower in the testosterone group. But we need to look at the confidence interval. This tells us the range the number could fall within if we were to repeat the study multiple times. In this case, the range goes from the testosterone group having 22% fewer problems to 17% more. Collecting more data would allow us to narrow down that range. This would give us more confidence about the actual impact of testosterone therapy. But for now, this study tells us it is unlikely to be worse than a 17% increase—which would still be significant.
Surprisingly, the study design allowed for the conclusion that testosterone therapy was no worse than placebo even if it increased the incidence of heart problems by 50% [15].
And there are further issues. The study had a very high dropout rate. About 62% of those in the testosterone group stopped treatment before the study was over [16]. That means a majority of the testosterone group didn’t actually complete the therapy the study was supposed to evaluate.
Also, therapy did not succeed in getting testosterone levels into the target range for many of the men in the trial [17]. An expert researcher on heart disease, Dr. Matthew Budoff, rightly asks how we can conclude that testosterone therapy is safe given that most men were treated only to a low-normal testosterone level, with short and incomplete follow-up, and large discontinuation rates [18].
So, despite the results of the TRAVERSE trial, the evidence we have now still points toward caution.
Section 4: Takeaways
What are the key takeaways, then? If we’re over 50 and considering testosterone therapy, what do we need to keep in mind?
Despite the controversy about the TRAVERSE trial, the consensus now is to stick to the clinical guidelines we looked at above. We should only consider testosterone therapy for those with clinically low testosterone levels and symptoms that go along with it—like a low sex drive and depressed mood.
There’s an important point to add, however. We need to investigate why testosterone is low. For example, lower levels can be driven by obesity. One study found a BMI over 30 was associated with nearly nine times the risk of low testosterone [19]. Diabetes and chronic illness can also lower our levels. We should evaluate and address these issues first, if possible.
Losing weight and doing resistance exercise are a must, and definitely should be done before considering adding testosterone therapy.
Close
If you really want to look at other ways to boost testosterone, there is another path. We’ve all seen the supplements promising to do this, but not all claims are backed up by evidence.
One supplement that does have good evidence for boosting testosterone and improving athletic performance is betaine (also called TMG). That’s why I include it in MicroVitamin. But just because I take a supplement in no way means you have to.
References
Below are the links to the studies referenced in this article. The text quoted from them in the original script has been removed, and only in-line citations appear above.
1. https://www.uptodate.com/contents/clinical-features-and-diagnosis-of-male-hypogonadism
2. https://www.uptodate.com/contents/clinical-features-and-diagnosis-of-male-hypogonadism
3. https://pmc.ncbi.nlm.nih.gov/articles/PMC3064036/
4. https://pubmed.ncbi.nlm.nih.gov/9024227/
5. https://pubmed.ncbi.nlm.nih.gov/9253305/
6. https://pubmed.ncbi.nlm.nih.gov/26886521/
7. https://pmc.ncbi.nlm.nih.gov/articles/PMC11562514/
8. https://pmc.ncbi.nlm.nih.gov/articles/PMC7880314/
9. https://pubmed.ncbi.nlm.nih.gov/28241355/
10. https://pmc.ncbi.nlm.nih.gov/articles/PMC5690890/
11. https://pmc.ncbi.nlm.nih.gov/articles/PMC5690890/
13. https://www.uptodate.com/contents/approach-to-older-males-with-low-testosterone
14. https://www.uptodate.com/contents/approach-to-older-males-with-low-testosterone
15. https://www.nejm.org/doi/full/10.1056/NEJMoa2215025
16. https://www.jacc.org/doi/10.1016/j.jacadv.2023.100742
17. https://www.jacc.org/doi/10.1016/j.jacadv.2023.100742
18. https://www.jacc.org/doi/10.1016/j.jacadv.2023.100742
19. https://academic.oup.com/jcem/article-abstract/95/4/1810/2597149
1 comment
Good article on the pros and cons. My experience at 75 years was that TRT took my T from 202 to 1100 (and Free T to optimal) within two months, with obvious improvements in my body composition/musculature. I have no cardiovascular issues (CAC score of zero), so I’m willing to live with the risk, given the clear benefits to fitness, mood, and libido.