TRT Side Effects: What to Know Before Starting Testosterone Replacement

Every prescription treatment has trade-offs, and TRT is no exception. The side effects of testosterone replacement therapy are well-documented and largely manageable when treatment is monitored appropriately — but they are real, and they shape who TRT is and isn't appropriate for. This guide walks through what to expect, what to watch for, and how monitoring works in Singapore.

For background on what TRT is and how it works, see our TRT explainer.

The headline trade-offs

For most men appropriately selected for TRT and monitored well, the benefits substantially outweigh the side effects. But "appropriately selected" and "monitored well" do a lot of work in that sentence. Understanding what could happen — and what is being watched for — is part of being an informed patient.

1. Effects on fertility

This is the most important consideration for men of reproductive age. TRT suppresses sperm production, often substantially. The mechanism is the natural feedback loop: when the body detects adequate testosterone, it reduces the pituitary signals (LH and FSH) that drive sperm production in the testes.

Men who wish to have children in the foreseeable future should discuss this with their doctor before starting TRT. There are alternative approaches — selective oestrogen receptor modulators like clomiphene, or human chorionic gonadotropin — that can raise testosterone while preserving fertility in some men. The conversation about fertility should happen at the start, not after treatment is underway.

2. Cardiovascular considerations

Cardiovascular safety has been the most debated topic in TRT in the past decade. Earlier observational studies raised concerns, while subsequent randomised trials painted a more reassuring picture.

The 2023 TRAVERSE trial, published in the New England Journal of Medicine, was the largest randomised trial of TRT cardiovascular safety to date. It studied over 5,000 men with hypogonadism and existing cardiovascular risk over an average of three years. The result: TRT did not significantly increase the risk of major adverse cardiovascular events (heart attack, stroke, cardiovascular death) compared with placebo.

Current guidance from the Endocrine Society and the American Urological Association (both updated post-TRAVERSE) is that TRT, when appropriately indicated and monitored, does not appear to substantially increase cardiovascular risk for most patients. This remains an active area of research, and individual cardiovascular risk should be factored into any decision.

3. Prostate considerations

TRT is contraindicated in men with active prostate cancer. For men without prostate cancer, current evidence does not suggest that TRT causes prostate cancer, though it can sometimes accelerate the growth of pre-existing undiagnosed disease.

Standard practice in Singapore is to screen prostate health before starting TRT (PSA, digital rectal exam where appropriate) and to monitor PSA periodically during treatment. If PSA rises significantly, further evaluation is undertaken.

4. Polycythaemia (high red blood cell count)

Testosterone stimulates red blood cell production. On TRT, haematocrit (the percentage of blood that is red blood cells) can rise above the normal range — a condition called polycythaemia. Significant polycythaemia raises the risk of blood clots and stroke.

This is one of the most commonly seen side effects of TRT and one of the main reasons regular monitoring is important. If haematocrit rises significantly, the dose can be reduced, the formulation can be changed, or in some cases, blood donation (therapeutic phlebotomy) is recommended.

5. Skin reactions (gel formulations)

Topical testosterone gel can cause skin irritation, redness, or rash at the application site. This is usually mild and manageable.

A more important consideration with gels is skin-to-skin transfer. Testosterone from the application site can transfer to other people through close contact, particularly before the gel has fully absorbed. This is a risk for women (pregnancy and adult contact) and children (development). Practical guidance: wash hands after application, allow the gel to dry, cover the application site, and avoid skin-to-skin contact with women and children for several hours after application.

6. Mood and behaviour

For most men with hypogonadism, TRT improves mood, motivation, and emotional steadiness. In some men, particularly at higher doses or in the early weeks of treatment, there can be transient irritability, agitation, or sleep disruption. These usually settle with dose adjustment.

7. Other considerations

• Acne and oily skin can occur, particularly in younger men.
• Mild fluid retention in some men, particularly at the start.
• Sleep apnoea can be worsened by TRT, which is why pre-existing sleep apnoea is treated first.
• Gynaecomastia (development of breast tissue) can occur due to aromatisation of testosterone to oestrogen, particularly in men with higher body fat.
• Testicular atrophy — mild reduction in testicular size as the body's own production is suppressed. Usually reversible if treatment stops.

What standard monitoring looks like in Singapore

A typical monitoring schedule for a man on TRT:

• At 6 weeks: testosterone level, full blood count, symptom review
• At 3 months: testosterone level, FBC, PSA (if relevant), symptom review
• At 6 months and then 6–12 monthly: testosterone level, FBC, PSA (if relevant), full review

If any results trigger concern — rising haematocrit, rising PSA, new symptoms — the schedule tightens and additional investigation follows.

When to call your doctor

Some things on TRT warrant reaching out to your doctor between scheduled checks:

• Chest pain, shortness of breath, calf pain or swelling (possible blood clot or cardiovascular event)
• Sudden severe headache or vision changes
• Significant new or worsening urinary symptoms
• Marked irritability, mood change, or sleep disruption
• Skin rash that is significant or spreading

Frequently asked questions

Is TRT safe long-term?

When appropriately indicated, dosed, and monitored, TRT is considered a well-established long-term treatment for men with confirmed hypogonadism. It is not without risks, but the framework for managing those risks is well-defined.

Will TRT increase my risk of heart attack?

The 2023 TRAVERSE trial — the largest randomised study of TRT cardiovascular safety — did not find a significant increase in major adverse cardiovascular events compared with placebo, in men with hypogonadism and existing cardiovascular risk. Current guidance reflects this, while continuing to advise individualised risk assessment.

Can TRT cause prostate cancer?

Current evidence does not suggest that TRT causes prostate cancer. TRT is, however, contraindicated in men with active prostate cancer, and PSA monitoring is part of standard care during treatment.

What's the most common side effect?

Polycythaemia (rising red blood cell count) is one of the most commonly monitored and managed side effects, particularly with injectable testosterone. Most cases respond to dose adjustment or formulation change.

Can I stop TRT if I get side effects?

Yes — with your doctor. TRT can be paused, the dose adjusted, or the form changed. Stopping abruptly without medical guidance is not recommended.

Speak to a Singapore-licensed doctor on Noah

If you are considering TRT or already on it and want to discuss side effects or monitoring, you can book a confidential consultation with a Singapore-licensed doctor on Noah.