TRT Side Effects: What to Expect

Testosterone replacement therapy is generally well-tolerated when properly supervised, but like any medical treatment, it carries potential side effects. Understanding these risks — and how they're monitored — is an important part of making an informed decision about treatment.

Common side effects

Erythrocytosis (increased red blood cells)

This is the most clinically significant side effect of TRT. Testosterone stimulates red blood cell production, which can increase haematocrit — the percentage of your blood volume occupied by red blood cells. Elevated haematocrit thickens the blood and can increase the risk of blood clots. According to research published in the National Library of Medicine, therapeutic phlebotomy (controlled blood donation) is indicated if haematocrit exceeds 52%.

How it's managed: Regular blood tests monitor haematocrit. If levels rise too high, your GP will adjust the dose or pause treatment. This is why ongoing blood work is non-negotiable.

Oestrogen conversion

Testosterone is partially converted to oestradiol (a form of oestrogen) by the aromatase enzyme, particularly in fat tissue. Elevated oestrogen can cause fluid retention, breast tenderness, and in some cases gynaecomastia (breast tissue growth).

How it's managed: Oestradiol is monitored on blood tests. If levels rise excessively, your GP may adjust the testosterone dose. In rare cases, aromatase inhibitors may be considered.

Acne and oily skin

Testosterone increases sebum production, which can trigger acne — particularly on the back and shoulders. This is more common in the first few months of treatment and often settles.

How it's managed: Topical treatments, dose adjustment if severe.

Testicular atrophy

When you supply testosterone externally, the pituitary gland reduces LH and FSH production, which causes the testes to shrink. This is a predictable physiological response, not a sign of damage.

How it's managed: For men concerned about fertility, enclomiphene preserves testicular function. Some clinicians use low-dose hCG alongside TRT to maintain testicular size.

Less common side effects

Sleep apnoea

TRT may worsen existing sleep apnoea in some men. If you snore heavily, experience daytime sleepiness, or have been diagnosed with sleep apnoea, your GP should be aware before starting treatment.

Mood changes

While most men report improved mood on TRT, some experience irritability, particularly if testosterone levels spike too high or fluctuate significantly between doses. This is more common with injectable formulations and often resolves with dose adjustment.

Injection site reactions

For men using Reandron (intramuscular injection), localised pain, swelling, or itching at the injection site can occur. A rare but serious reaction called pulmonary oil microembolism can cause coughing immediately after injection — this is self-limiting but should be reported to your GP.

What the research says about cardiovascular risk

The relationship between TRT and cardiovascular risk has been extensively studied. A large body of evidence, including recent reviews published in peer-reviewed journals, indicates that TRT does not increase the risk of major cardiovascular events when administered under proper medical supervision and within therapeutic ranges. However, monitoring blood pressure, haematocrit, and lipids remains essential. For more detail, see our article on TRT and heart health.

What about prostate cancer?

TRT does not cause prostate cancer. This concern originated from decades-old hypotheses that have been largely disproven by modern research. However, TRT can stimulate growth of existing prostate tissue, which is why a baseline PSA test is taken before starting treatment and monitored regularly. According to Healthdirect Australia, PSA testing is an important screening tool that helps detect prostate changes early.

Fertility impact

TRT suppresses the hypothalamic-pituitary-gonadal axis, reducing or eliminating sperm production. This effect is usually reversible after stopping TRT, but recovery can take months and may not be complete in all men. For men planning families, enclomiphene is an alternative that preserves fertility while raising testosterone.

Why monitoring matters

Nearly all TRT side effects are manageable — the key is catching them early through regular blood work. A responsible TRT provider will monitor you every 8–12 weeks initially, then every 6 months, checking testosterone levels, haematocrit, PSA, oestradiol, liver function, and lipids.

This is exactly why we require ongoing GP supervision — and why subscription platforms that skip proper monitoring are doing their patients a disservice.