Weekly or three-monthly testosterone injections: what changes for level stability and monitoring

The big difference between frequently dosed injectable testosterone and the three-monthly option is how blood levels move. Short-acting esters such as cipionate cause peaks above the normal range after each injection, then dips before the next one. Long-acting undecanoate is given every 10 to 14 weeks and, at the correct dose, does not keep levels high for long. That difference matters for the main side effect doctors monitor: a rise in haematocrit. Both options need follow-up blood tests.

Before comparing them, one point needs to be clear. The data below come from summaries of product characteristics (SmPCs), a review and a clinical guideline. No trial has compared the two regimens head to head, so this comparison draws on several different sources.

What "weekly" and "three-monthly" actually mean in Spain

Two injectable testosterone esters for intramuscular use are authorised in Spain by the AEMPS. The first is testosterone cipionate (Testex Prolongatum), which is short-acting. It comes in two strengths: 100 mg in 2 ml, equivalent to 70.0 mg of testosterone, and 250 mg in 2 ml, equivalent to 174.8 mg. It is injected slowly into a muscle.

The second is testosterone undecanoate (Reandron 1000 mg), which is long-acting. Each ampoule contains 1000 mg in 4 ml, that is 250 mg per ml and 631.5 mg of testosterone. According to its Spanish SmPC, one ampoule is given every 10 to 14 weeks, also by slow intramuscular injection. This is what people mean when they talk about the three-monthly regimen.

A weekly regimen does not appear in any Spanish SmPC, according to the report this article is based on. When people talk about weekly injections, they usually mean short-acting esters given frequently, but that frequency is not listed as an authorised regimen. Any specific dosing interval is decided by the doctor managing the case.

Level stability: peaks and troughs versus a flatter curve

According to a review on testosterone-associated erythrocytosis, short-acting esters push testosterone above the normal range for the days following the injection. Levels then fall until the next dose. Many people notice this swing in their energy, mood or libido over the course of each cycle.

Giving smaller injections more often aims to smooth out that curve, but it does not remove the peaks. With any short-acting ester there is a rise after every dose. Undecanoate, at the correct dose, does not keep levels high for long. That is why it is considered the most stable of the injectable options.

Side effects: why haematocrit makes the difference

Haematocrit is the percentage of your blood made up of red blood cells. Testosterone raises it, and once it goes above 54% this is called erythrocytosis. The Endocrine Society's 2018 guideline estimates that men treated with testosterone have a relative risk of erythrocytosis of 8.14 compared with untreated men.

The route of administration matters. The same review notes that short-acting injectables carry a higher risk of erythrocytosis than other forms. Enantate carries the highest risk, while patches and gels carry the lowest. This is linked to those above-normal peaks. The evidence is not conclusive on whether injecting twice a week avoids the problem, so you cannot assume it does. If you want to know which figures are a concern and how this is managed, we explain it in high haematocrit on testosterone: at what level it becomes a concern.

As for the heart, the TRAVERSE trial followed 5,246 men with hypogonadism and either high cardiovascular risk or existing cardiovascular disease. Major cardiovascular events occurred in 7.0% of those treated with testosterone and 7.3% of those given placebo. The difference was not significant. Even so, testosterone was associated with more atrial fibrillation, more acute kidney injury and more pulmonary embolism. In other words, there was no increased risk of major events, but that does not mean the treatment is harmless. TRAVERSE did not compare regimens or esters, so it cannot help you choose between them.

Monitoring: what is checked with each regimen

The first check comes before you start. The SmPC requires male hypogonadism to be confirmed by both symptoms and blood tests before any testosterone treatment is started. We go through it step by step in which blood tests you need before testosterone is prescribed.

Once treatment has started, the Endocrine Society guideline recommends measuring haematocrit at baseline and again at 3 to 6 months. If it goes above 54%, testosterone is stopped until it returns to normal and then restarted at a lower dose. This applies to both regimens. An injection every three months does not mean you can skip blood tests: your individual response still needs checking, just as with the frequent regimen.

What does change is how the results are interpreted. With a short-acting ester, the testosterone reading depends heavily on which day of the cycle the blood is taken. The exact timing of the blood test for each ester is set by the doctor managing your follow-up.

Practicalities, cost and access in Spain

Day to day, the short-acting regimen means more injections and more appointments or self-injections, with the advantage that the dose is easier to adjust. Undecanoate means just a few injections a year. As it is 4 ml of solution, it is injected slowly into a muscle. If you are also weighing up injections against gel, you will find the comparison in testosterone gel vs injections.

The sources verified for this article do not include the price of either product, so we do not give figures. Both are prescription-only medicines in Spain.

When each one is considered, in general terms

Before choosing a regimen, the diagnosis has to be confirmed. The European Male Ageing Study used strict criteria: at least three sexual symptoms, total testosterone below 11 nmol/L and free testosterone below 220 pmol/L. On those criteria, late-onset male hypogonadism affects around 2.1% of European men aged 40 to 79. It is far less common than the word andropause suggests. If the symptoms sound familiar, start with low testosterone: the real symptoms and when to worry.

Once the diagnosis is confirmed, the long-acting option is usually considered when stable levels and fewer injections are the priority. The short-acting option makes sense when more flexibility is needed to adjust the dose or test the response. In every case, any history of high haematocrit, cardiovascular risk and personal preferences are assessed individually.

Key takeaways and next step

The three-monthly injection gives more stable levels, while the short-acting option produces peaks and troughs. Neither gets you out of haematocrit monitoring, which is the side effect most closely watched, and a weekly regimen does not appear in the Spanish SmPC. In Spain you can now access men's hormone health treatment with a prior assessment, blood tests to confirm the diagnosis and, where appropriate, a prescription from a registered doctor with ongoing follow-up; that is what AiON offers. You can:

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