Does TRT Work? Clearly For Sex Drive. Not At All For Energy.

This is the part of the series where something works.

After five pages of supplements that do not do what the label says, testosterone replacement therapy is the intervention with real trials behind it and a real effect. It is also the one with a bill attached, and the bill includes a result from 2024 that almost nobody saw coming.

What it definitely does

In 2016 the National Institutes of Health published the Testosterone Trials: 790 men aged 65 and over, all with testosterone under 275 ng/dL and symptoms, randomised to testosterone gel or placebo gel for a year. [1]

Treatment lifted their testosterone into the mid-normal range for men aged 19 to 40. And it “significantly increased sexual activity… as well as significantly increased sexual desire and erectile function” (P < 0.001). [1]

That finding has held up under much harder scrutiny since. In 2023 a team went back to 35 trials covering 5,601 men and, crucially, obtained the individual participant data from 17 of them — the raw per-man records rather than the published averages. That is the strongest form a meta-analysis takes. [2]

Testosterone raised scores on the International Index of Erectile Function by 5.52 points, and the erectile function subscore by 2.14 — enough to reach what researchers call the minimal clinically important difference for mild erectile dysfunction. In plain terms: not just a number moving, but a change big enough that a man would notice it. [2]

And the accompanying health technology assessment, working from the same dataset, found testosterone “improved quality of life and sexual function in almost all patient subgroups.” [3]

Who it works for — and a distinction worth holding on to

The individual-data analysis was able to ask a question the averages cannot: does it matter who you are?

The improvement itself was “not found to be dependent on participant age, obesity, presence of diabetes, or baseline serum total testosterone.” [2] Older men benefited. Heavier men benefited. Men who started only mildly low benefited about as much as men who started very low.

But the same paper adds something that gets lost: the absolute level reached during treatment did depend on age and starting testosterone. [2]

Those are two different statements and both are useful. The size of the improvement is roughly the same for everyone. Where you end up is not — because men who are older or heavier start from worse symptoms, and the same improvement from a lower floor lands lower.

What it does not do — including the thing men come in for

Here is the part the clinics tend not to lead with.

The T-Trials had a Vitality Trial specifically to test energy and fatigue. Result: “no significant benefit with respect to vitality, as assessed by the Functional Assessment of Chronic Illness Therapy-Fatigue scale.” [1]

The individual-data meta-analysis, across all 35 trials: testosterone “did not significantly improve psychological symptoms” on the Beck Depression Inventory. [2] The T-Trials did find “slightly better mood” — slightly is the word the paper uses. [1]

Walking is the honest middle case. The Physical Function Trial asked whether more men could improve their six-minute walking distance by at least 50 metres. Within that trial, no significant difference. Pooled across all three trials, there was one: 20.5% versus 12.6%. [1] Both numbers are in the paper and both belong in any summary of it.

If you arrived here from part two, this should sound familiar. The European ageing study found that only three sexual symptoms clustered with low testosterone — not fatigue, not low mood. Treatment turns out to fix roughly the same list that low testosterone actually predicts. The tiredness was never the hormone.

The result nobody expected

Testosterone improves bone density. That has been known for years, it is the opening sentence of the paper we are about to describe, and it is why people assumed it would prevent fractures.

In 2024, researchers counted the fractures. Inside the big cardiovascular safety trial, 5,204 men were followed for a median of 3.19 years, with every reported fracture checked against medical records. [4]

Fractures occurred in 3.50% of the testosterone group and 2.46% of the placebo group. Hazard ratio 1.43, confidence interval 1.04 to 1.97. And the paper adds that the incidence “also appeared to be higher in the testosterone group for all other fracture end points.” [4]

More testosterone. Better bones on a scan. More broken bones in real life.

This is the third time in this series we have run into the same trap. Ashwagandha lowered cortisol without making anyone feel less stressed. A testosterone number can read normal while the man has symptoms. And now bone density — the thing you can measure easily — improves while the thing you actually care about gets worse.

Nobody knows why. One reasonable guess is that men who feel better move more, and men who move more fall over more, but that is a hypothesis and the paper does not establish it. What the paper establishes is that if you were told testosterone would protect your bones, the only trial big enough to check found the opposite.

Worth noting who ran it: that subtrial and its parent were funded by AbbVie, which sells testosterone. The manufacturer-funded trial produced the least flattering result in this whole page, which is not the direction industry funding is usually assumed to push.

The costs that are certain

Fertility. This one is not a risk, it is a mechanism. Taking testosterone tells your brain to stop asking your testes to make it, which collapses the testosterone concentration inside the testicle — and that is what sperm production runs on. A 2025 review puts it plainly: exogenous testosterone “drastically reduces intratesticular testosterone, consequently impairing spermatogenesis”, and “is contraindicated in men trying to conceive.” [6]

Production usually restarts after stopping, but with “highly variable kinetics that might complicate family planning.” [6] Usually. Variable. If you are 35 and not finished having children, that is the sentence to read twice.

The cardiovascular question, answered. This used to be the great worry. It has now been tested properly: in 5,246 men at high cardiovascular risk followed for a mean 33 months, major cardiovascular events occurred in 7.0% on testosterone and 7.3% on placebo. [5] The evidence synthesis agrees — 7.5% versus 7.2%, odds ratio 1.07, and its conclusion is that the findings “do not support a relationship between testosterone replacement therapy and cardiovascular/cerebrovascular events in the short-to-medium term.” [3]

And the list of men who should not start. The Endocrine Society names them: men planning fertility in the near term, men with breast or prostate cancer or a suspicious prostate exam or PSA, elevated haematocrit, untreated severe sleep apnoea, severe urinary symptoms, uncontrolled heart failure, a heart attack or stroke in the last six months, or a clotting disorder. [7] Monitoring afterwards is not optional either.

About “before and after”

A lot of people arrive at this question through photographs. It is worth saying what the trials did and did not measure.

They measured sexual function questionnaires, walking distance, fatigue scales, mood inventories, cardiovascular events and fractures. They were not photograph studies, and a photograph cannot tell you what a man was eating, lifting or taking alongside the prescription.

The honest before-and-after is the table at the top of this page.

The verdict

Testosterone therapy works, for a specific list of things, in men who genuinely have low testosterone and symptoms to go with it. We rate it Supported: a 790-man NIH trial and an individual-participant meta-analysis of 35 trials both find a clinically meaningful improvement in sexual function and quality of life, and the cardiovascular alarm has been properly tested and did not ring.

It is not Established, because the benefit does not extend to the complaints most men bring — energy and mood — and because the largest trial to count fractures found 43% more of them on treatment.

So the useful framing is not “does TRT work”. It is: for what, and at what cost. If you have two confirmed low morning readings and the sexual symptoms that actually track with them, the evidence says treatment helps and the heart worry has been retired. If what you have is tiredness, the trial designed to test that found nothing. And if you want children in the next few years, this is the wrong drug.

It is also worth remembering what the rest of this series found. No supplement comes close to this, and losing weight does about as much to your number as anything you can buy — with no fracture signal and no effect on your fertility.

Part 8 of a series on testosterone. Earlier: whether to get tested, what normal means, free versus total, what actually raises it, and whether boosters work.

Related: should you get your testosterone tested · normal testosterone levels by age · how to increase testosterone naturally · do testosterone boosters work