Testosterone therapy for older men has surged in popularity. For those considering it — or those who know someone who has — this guide cuts through the confusion. There have been sharp disagreements among researchers and clinicians about its benefits, risks, and who should actually be using it.
By the end of this article, readers will have the insights needed to make an informed decision about testosterone therapy. This covers the fascinating history of testosterone treatment, what the best science currently says, and a controversy around a major new trial that is reshaping how clinicians think about this topic.
Table of Contents
1. History
4. Takeaways
5. References
Section 1: History
The effects of testosterone have been observed for a very long time. People understood that the testes produced something that had a large impact on behavior. In the ancient world, castration was sometimes used to make slaves more passive and obedient. It was also used to keep males from going through puberty in order to preserve their singing voice.
Noticing these effects, people from Roman times tried eating animal testes to increase energy and sexual function. French scientist Charles E. Brown-Séquard tried a more sophisticated version of this approach in the late 1800s. He gave himself daily injections of a mixture extracted from animal testes and claimed dramatic results — reporting restored strength and increased energy.
As is now understood, this could only have been a placebo effect. That crude approach could not actually work. Researchers were on the right track, but the science had a long way to go. The critical missing piece was identifying what in the testes explained their effect on the body.
Real progress began 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, comparing their behavior. Those who received the transplants had normal male rooster behaviors restored; the others did not. His conclusion 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 would now be called a hormone.
In the early 1900s, researchers learned more about hormones and how they work in the body. They began to identify and isolate them chemically. The major breakthroughs came in the 1930s. Scientists finally identified the crucial hormone produced by the testes and named it "testosterone." In the same decade, they figured out how to synthesize testosterone in the laboratory.
The next question was: could this testosterone be used to treat men whose levels were low? And if so, how? This turned out to be harder than expected.
Taking testosterone orally did not work — it was broken down by the liver and never reached adequate blood levels. A different oral form was developed that appeared effective, but was later found to have toxic effects on the liver.
Testosterone was also delivered by injection. That approach worked better. But until the 1970s, there was no reliable way to measure testosterone levels in the blood. Clinicians were aiming for "normal" without being able to confirm whether they had reached it.
Once new testing methods became available, a problem emerged. All of the testosterone delivery methods then in use produced levels that were either too high or too low. A better delivery system was needed.
That came in the 1990s with a skin patch. This finally provided a way to reliably achieve normal testosterone levels. Several other reliable methods are in use today, including gels and injections.
This was a significant development — clinicians could now accurately measure testosterone levels and raise them in men when they were genuinely low.
But two problems quickly followed. First, testosterone treatment surged in popularity. Health influencers began promoting its benefits for improving strength, energy, and sexual function. Men started using it even when their testosterone levels were not clinically low. Second, new data emerged suggesting testosterone therapy could carry dangerous adverse effects.
Section 2: The Present Consensus
Where does that leave things now? Below is a review of what current clinical guidelines say about who should consider testosterone therapy and what the real risks are — followed by an examination of the major new trial and the controversy it has stirred.
1. Who Is an Appropriate Candidate?
Current guidelines rest on three important considerations. First, unusually low testosterone levels are known to have negative effects. The first to appear are decreased energy, a weaker sex drive, and a depressed mood [1]. If low testosterone persists for years, it can also lead to decreases in muscle mass and body hair [2]. Testosterone therapy can counteract some of these problems.
Studies have found therapy can improve libido and sexual function [3]. It can also improve muscle mass and strength. In one study, 10 weeks of testosterone therapy increased fat-free mass, muscle volume, and the maximum weight participants could lift [4]. Testosterone therapy can also 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 when a person has symptoms of low testosterone, therapy can help correct them. That is the first important consideration underlying current guidelines.
2. What If Testosterone Levels Are Not Abnormally Low?
The second consideration: there is not yet good evidence about the benefits of testosterone therapy for those whose levels are not abnormally low.
The word "abnormal" matters here. Testosterone levels naturally fall with age [7]. An older man will have testosterone levels significantly lower than a young man — but this does not mean his levels are low in a clinical sense. In other words, the levels may not fall to a threshold where major health issues occur.
Clinically low testosterone levels that cause symptoms are usually due to problems with the testes themselves or with the region of the brain that controls testosterone production.
As awareness has grown that testosterone declines with age and affects things like sexual function, many men whose levels are not abnormally low are pursuing therapy. Prescription sales of testosterone ballooned from $100 million in 2000 to about $2.7 billion by 2013, and they have continued to rise [8]. But most research has been conducted in men with genuinely low testosterone and with symptoms. Whether therapy can benefit those simply experiencing the normal age-related decline — without clinical deficiency — is a question current evidence cannot yet answer.
The reflexive response — "even if it does nothing, it might help, so why not try?" — runs into the third consideration: the risks associated with testosterone therapy.
3. Risks of Testosterone Therapy
One study found testosterone therapy is linked to an increase in plaque in the arteries [9]. Therapy can also raise red blood cell counts — a condition called erythrocytosis — which is the most common adverse effect of testosterone therapy [10]. Erythrocytosis increases blood viscosity, and the concern is that this thickening of the blood could contribute to higher blood pressure, blood clots, and an increased risk of heart attacks [11]. Data on those using testosterone therapy correctly have not clearly demonstrated a higher risk of these outcomes, but the evidence is mixed and inconclusive. Both the Endocrine Society and the FDA have issued formal warnings about the potential cardiovascular risks of testosterone therapy [12].
Taking these three considerations together, clinical guidelines recommend testosterone therapy only for those who have clinically low levels along with symptoms — such as low sex drive and depressed mood [13]. The reasoning is that this approach balances confidence in benefits with awareness of risks. The guidelines recommend against testosterone therapy in older men who do not have symptoms or whose levels are not clinically low, because in those cases the risks are known but the benefits are unclear [14].
Section 3: The Controversy
A major new trial has generated significant controversy, with results that some believe require a fundamental revision of the logic above.
The study was the TRAVERSE trial [15]. It centres on the question of cardiovascular risk. It enrolled over 5,000 middle-aged to older men with pre-existing heart disease or a high risk of it. These men also met the standard criteria for testosterone therapy: they had clinically low testosterone and symptoms of deficiency. After approximately two years of treatment, researchers followed participants for a further three years, looking for cardiovascular events including heart attacks and strokes.
The findings: 7% of patients taking testosterone experienced heart attacks or strokes during the study — a figure that sounds high. But the rate in the placebo group was 7.3%. The researchers concluded that testosterone replacement therapy was no worse than placebo in terms of causing heart problems [15].
At first glance, this appears to have major implications. If testosterone therapy does not actually increase the risk of heart problems, clinicians may not need to be as cautious when prescribing it. Some have even suggested that more men could be offered therapy, even where benefits remain unclear.
But does the TRAVERSE trial really show that cardiovascular concerns are overblown?
That is certainly how some have interpreted it. Experts at a recent conference on testosterone treatment claimed the study "can finally put to rest the anecdotal and wholly unproven fear physicians have that testosterone therapy will cause heart disease." A closer look, however, reveals important limitations.
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 the confidence interval is critical. This tells us the range of results that could be expected if the study were repeated multiple times. In this case, the range extends from the testosterone group having 22% fewer problems to 17% more. Collecting more data would narrow that range and provide greater confidence about the true effect of testosterone therapy. For now, this study only establishes that therapy is unlikely to be worse than a 17% increase in cardiovascular events — which would still be clinically significant.
Notably, 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].
There are further methodological concerns. The study had a very high dropout rate. Approximately 62% of those in the testosterone group stopped treatment before the study concluded [16]. That means a majority of the testosterone group did not actually complete the therapy the trial was designed to evaluate.
Therapy also did not succeed in getting testosterone levels into the target range for many of the men in the trial [17]. Cardiovascular researcher Dr. Matthew Budoff raises a pointed question: how can the safety of testosterone therapy be concluded when most men were treated only to a low-normal testosterone level, with short and incomplete follow-up, and large discontinuation rates [18]?
Despite the TRAVERSE trial's headline findings, the totality of current evidence still points toward caution.
Section 4: Takeaways
For men over 50 considering testosterone therapy, what are the most important evidence-based takeaways?
Despite the controversy around the TRAVERSE trial, the current consensus is to adhere to the clinical guidelines above. Testosterone therapy should be considered only when testosterone levels are clinically low and symptoms are present — such as reduced libido and depressed mood.
There is an important additional step: investigating why testosterone is low. 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 testosterone levels. These underlying issues should be evaluated and addressed first, where possible.
Weight loss and resistance exercise are the most evidence-based first-line approaches, and should be undertaken before considering testosterone therapy.
Natural Testosterone Support: What the Evidence Says
For those looking beyond lifestyle changes, some supplements have been studied for their effects on testosterone and physical performance. Most marketed products lack robust clinical evidence — but there are exceptions.
Betaine (also called trimethylglycine, or TMG) has research supporting effects on both testosterone levels and athletic performance. At higher doses, betaine combined with exercise has improved strength and body composition beyond what exercise alone achieves in clinical trials. In a 2013 JISSN study by Cholewa et al., participants supplementing with betaine showed significantly greater gains in lean mass and strength compared to placebo over a 6-week resistance training programme. A 2021 JISSN study by Arazi et al. in soccer players found betaine supplementation improved both performance and hormonal markers. TMG is also a methyl donor that supports the homocysteine-lowering pathway alongside methylated B vitamins — relevant because elevated homocysteine is associated with cardiovascular and cognitive risk in older adults.
From the MicroVitamin range
MicroVitamin includes 500 mg of TMG (betaine anhydrous) per daily serving alongside methylated B12 and folate, supporting the homocysteine-lowering pathway studied in clinical trials. MicroVitamin.
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.
- https://www.uptodate.com/contents/clinical-features-and-diagnosis-of-male-hypogonadism
- https://www.uptodate.com/contents/clinical-features-and-diagnosis-of-male-hypogonadism
- https://pmc.ncbi.nlm.nih.gov/articles/PMC3064036/
- https://pubmed.ncbi.nlm.nih.gov/9024227/
- https://pubmed.ncbi.nlm.nih.gov/9253305/
- https://pubmed.ncbi.nlm.nih.gov/26886521/
- https://pmc.ncbi.nlm.nih.gov/articles/PMC11562514/
- https://pmc.ncbi.nlm.nih.gov/articles/PMC7880314/
- https://pubmed.ncbi.nlm.nih.gov/28241355/
- https://pmc.ncbi.nlm.nih.gov/articles/PMC5690890/
- https://pmc.ncbi.nlm.nih.gov/articles/PMC5690890/
- https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-cautions-about-using-testosterone-products-low-testosterone-due
- https://www.uptodate.com/contents/approach-to-older-males-with-low-testosterone
- https://www.uptodate.com/contents/approach-to-older-males-with-low-testosterone
- https://www.nejm.org/doi/full/10.1056/NEJMoa2215025
- https://www.jacc.org/doi/10.1016/j.jacadv.2023.100742
- https://www.jacc.org/doi/10.1016/j.jacadv.2023.100742
- https://www.jacc.org/doi/10.1016/j.jacadv.2023.100742
- https://academic.oup.com/jcem/article-abstract/95/4/1810/2597149
