Testosterone replacement therapy (TRT): what it is, how it is given and what to expect

Few topics in men's health generate as much noise as testosterone. Between the marketing of low testosterone and the promises of getting back your energy, your muscle or your youth, it is easy to lose sight of what the evidence actually supports. Let's go through it calmly: what testosterone replacement therapy (TRT) is, who it makes sense for, how it is given in Spain and what you can expect, with all the nuances and limits.

What TRT is and why it is considered

TRT is the hormone replacement therapy that supplies testosterone to a man whose body does not produce enough of it. It is not a supplement or a booster for healthy people: it is a treatment for a specific condition, male hypogonadism.

Hypogonadism is a clinical syndrome caused by a testosterone deficiency (and sometimes also a low sperm count) due to a failure of the testicles or of the axis that governs them in the brain, the so-called hypothalamic-pituitary-gonadal axis. It is classified into three types: primary, when the testicles themselves fail; secondary, when the signal coming from the hypothalamus or the pituitary fails; and functional, when there is no organic damage to the axis but it is held back by other conditions or circumstances.

The key point, and this is where marketing usually slips up, is that the diagnosis is not made with a single blood test. It requires two things at the same time: compatible symptoms or signs, and a low total testosterone confirmed on at least two morning blood samples using a reliable method. An isolated low reading, with no symptoms, does not define a disease and does not on its own justify treatment.

Age-related hypogonadism: what it is and how common it is

Testosterone tends to fall gradually over the years. The form more closely linked to age is called late-onset hypogonadism (LOH). The European Male Ageing Study, a landmark study in European men, defined it by the presence of three or more sexual symptoms (fewer morning erections, fewer sexual thoughts and erectile dysfunction) together with a total testosterone below 11 nmol/L (roughly 317 ng/dL) and a free testosterone below 220 pmol/L. In other words: symptoms plus blood results, not one or the other.

And how common is this? Far less common than the adverts suggest. In that same study, symptomatic late-onset hypogonadism (symptoms plus low testosterone) affected 2.1% of men aged 40 to 79. The figure rises with age: 0.1% between 40 and 49, 0.6% between 50 and 59, 3.2% between 60 and 69 and 5.1% between 70 and 79. Low testosterone on its own, without symptoms, is considerably more frequent, but by itself it is not a disease. Confusing the two is the basis of much of the overselling of TRT.

How testosterone is given

There is no single way of giving testosterone. The main routes are these:

• Transdermal: a gel applied to the skin daily. It tends to give more stable levels throughout the day.
• Short-acting intramuscular (testosterone enantate or cipionate): more frequent injections, with peaks after each dose and troughs before the next one.
• Long-acting intramuscular (testosterone undecanoate): an injection every 10 to 14 weeks or so.
• Subcutaneous: an injection under the skin.
• Subdermal implants or pellets: these release testosterone over several months.
• Oral (undecanoate): a formulation that can indeed be used. The classic 17-alpha-alkyl oral testosterones, such as methyltestosterone, are not used because of their liver toxicity.

Choosing one route over another is not a matter of commercial preference but a clinical decision that depends on each person's profile, on convenience, on how well the resulting levels are tolerated and on the monitoring required. It is an individual assessment and it is the doctor's call.

What is authorised in Spain

In Spain, the AEMPS authorises testosterone solely as replacement therapy for male hypogonadism when the deficiency has been confirmed clinically and biochemically, with two separate measurements. Authorised medicines include Reandron 1000 mg/4 ml (long-acting intramuscular testosterone undecanoate, given every 10 to 14 weeks or so) and the transdermal gels Testogel 50 mg and Testavan 20 mg/g. The classic oral undecanoate, Andriol Testocaps, does not appear in the AEMPS register of medicines.

One clarification is worth making: the more recent US oral formulations, marketed there as Jatenzo or Tlando, have no equivalent authorised under those brand names in Spain. All of these presentations are prescription-only medicines and can only be dispensed with a prescription. Anti-ageing, sporting or cosmetic uses are neither authorised nor publicly funded.

What the evidence says about benefits and safety

This is where we need to be especially honest, because the real benefit is narrower than what is usually promised.

Benefits: mainly in the sexual domain

The Testosterone Trials studied 790 men aged 65 or over with testosterone below 275 ng/dL and symptoms. One year of treatment with testosterone gel significantly improved sexual activity, desire and erectile function. By contrast, the benefit on six-minute walking distance, on vitality and fatigue and on physical function was modest or simply not significant in the trial specifically dedicated to it. Put simply: the clearest effect is seen in the sexual domain, not in some supposed general rejuvenation of strength and energy.

Cardiovascular safety: non-inferiority, not protection

The TRAVERSE trial, with 5,246 men aged 45 to 80 with symptomatic hypogonadism (two fasting testosterone readings below 300 ng/dL) and either existing cardiovascular disease or high risk, compared 1.62% testosterone gel with placebo. Testosterone proved non-inferior to placebo for major adverse cardiovascular events: 7.0% versus 7.3%, with virtually the same risk in both groups. No increase in prostate cancer was seen either.

It is important to read this result properly: it demonstrates relative safety, not benefit. TRT does not reduce heart attacks and does not protect the heart. And the same study detected, in the testosterone group, more cases of atrial fibrillation (an arrhythmia), pulmonary embolism and acute kidney injury. These are signals to keep in mind and monitor.

Risks that need monitoring

TRT is not harmless. It can cause an excessive rise in red blood cells (erythrocytosis or polycythaemia), so haematocrit and haemoglobin need to be checked. It can worsen sleep apnoea. And it means keeping an eye on PSA and the prostate. That is why diagnosis and follow-up involve measuring total testosterone fasting in the morning (between 7:00 and 10:00, because of its circadian rhythm), repeating a low reading before starting, and then monitoring haematocrit, PSA and the response of symptoms.

Common myths, dismantled

TRT is an anti-ageing or rejuvenating treatment. No. The FDA explicitly warns against its use for age-related low testosterone without an established cause. It is not indicated as a youth therapy, nor for sporting performance, nor for bodybuilding.

It helps fertility. Quite the opposite: testosterone given from outside the body suppresses sperm production, to the point of having a contraceptive effect. It is contraindicated in men trying to conceive, and in those cases other strategies are used, such as hCG or clomiphene.

Testosterone causes prostate cancer. TRAVERSE did not show any increase in prostate cancer. That said, this does not mean it is harmless for the prostate: it is contraindicated in active prostate cancer and in breast cancer in men, and it requires PSA monitoring.

It works for erectile dysfunction in any man. No. The sexual benefit was demonstrated in men with confirmed hypogonadism, not in men with normal testosterone. If levels are normal, TRT is not the answer to an erection problem.

One low blood test means you should start treatment. No. You need the combination of compatible symptoms plus two low morning measurements. A single low reading, with no symptoms, is not a disease.

In summary

TRT is an effective and reasonably safe treatment for one specific situation: male hypogonadism confirmed by symptoms and by blood tests. Its clearest benefit is in the sexual domain; when it comes to energy, strength or longevity, the promises outstrip the data. And it carries real risks that make medical follow-up essential. It is not a wellness product or an anti-ageing shortcut.

If you recognise yourself in these symptoms, the sensible step is not to self-diagnose or buy anything on your own: it is to measure it properly and decide with a doctor, without promises and without rushing. In Spain there is now men's hormonal health treatment with a prior assessment, a prescription from a registered doctor when appropriate and ongoing follow-up. If you want to start there, you can check whether you are eligible.