While Testosterone Replacement Therapy (TRT) is a highly effective treatment for hypogonadism, it is not without potential risks. Like any medical intervention that alters the endocrine system, TRT requires careful clinical oversight to manage its biological impact. In 2026, the focus has shifted from fearing the therapy to meticulously monitoring its effects on blood thickness, fertility, and organ health. When prescribed correctly and monitored by a physician, most side effects are either preventable or manageable.
What We Will Cover in This Article
- Erythrocytosis and the risk of thickened blood
- The impact of TRT on natural fertility and sperm production
- Dermatological side effects including acne and hair changes
- Oestrogen management and breast tissue sensitivity
- Cardiovascular and prostate health considerations in 2026
- Common localised reactions to different delivery methods
Blood Thickness: Erythrocytosis
The most common significant side effect of TRT is an increase in red blood cell production, known as erythrocytosis or polycythaemia.
Testosterone stimulates the kidneys to produce erythropoietin, which tells the bone marrow to make more red blood cells. While this can improve oxygen delivery, if the blood becomes too thick, specifically a high haematocrit, it can increase the risk of blood clots. In 2026, clinical protocols require regular full blood counts. If haematocrit levels exceed 54 percent, doctors may adjust the dosage or recommend therapeutic blood donation to keep the blood flowing safely.
Fertility and Testicular Changes
A frequently misunderstood risk of TRT is its impact on the body natural reproductive signalling.
- Sperm Production: Because TRT provides external testosterone, the brain detects high levels and stops sending the signals, LH and FSH, that tell the testes to work. This can lead to a significant drop in sperm count, effectively acting as a male contraceptive.
- Testicular Atrophy: Without these internal signals, the testes may decrease in size.
- The 2026 Solution: For men who wish to remain fertile or prevent atrophy, clinicians often prescribe HCG (Human Chorionic Gonadotropin) alongside TRT to maintain natural testicular function.
Oestrogen Conversion and Gynaecomastia
Testosterone naturally converts into oestradiol, a form of oestrogen, via the aromatase enzyme. When you increase testosterone levels, oestrogen levels often rise as well.
If oestrogen levels become too high, some men may experience nipple sensitivity or the development of breast tissue, known as gynaecomastia. Other symptoms of high oestrogen include water retention and mood swings. In 2026, we manage this by optimising the testosterone dose first, rather than automatically prescribing oestrogen blockers, as a certain amount of oestrogen is vital for bone and brain health.
Dermatological and Physical Side Effects
External hormones can affect the skin and hair follicles, particularly during the first few months of therapy as the body adjusts.
- Acne: Increased oil production in the skin can lead to breakouts, especially on the back and shoulders.
- Hair Loss: In men with a genetic predisposition to male pattern baldness, TRT can accelerate hair thinning by increasing DHT levels.
- Sleep Apnoea: TRT can worsen pre-existing obstructive sleep apnoea. In 2026, we screen patients for sleep issues before starting therapy to ensure respiratory safety.
Cardiovascular and Prostate Health
Two of the most historically debated risks are the heart and the prostate.
| Factor | 2026 Clinical Consensus |
| Prostate Health | TRT does not cause prostate cancer. However, it can stimulate the growth of an existing cancer. Regular PSA screening is mandatory. |
| Heart Health | Maintaining physiological levels of testosterone is generally considered heart protective. Risks primarily arise when doses are too high or when blood thickness is not managed. |
Localised Side Effects by Method
The delivery method you choose carries its own specific set of minor risks:
- Injections: Temporary pain, swelling, or bruising at the injection site.
- Gels: Skin irritation and the risk of accidental transfer to women or children through skin contact.
- Pellets: Risk of the pellet being extruded or pushed out by the body or minor infection at the site of the small incision.
To Summarise
The risks of TRT are largely predictable and manageable through a combination of correct dosing and regular blood monitoring. The most critical factors to watch in 2026 are red blood cell counts and the preservation of fertility. For most men, the benefits of restored energy, bone density, and metabolic health far outweigh the potential side effects, provided they remain under the care of a qualified physician.
If you experience sudden calf pain, shortness of breath, or a significant change in urinary habits while on therapy, contact your doctor immediately for a review.
Will TRT affect my mood?
For most men, TRT improves mood by reducing irritability and anxiety. However, if oestrogen or testosterone levels are too high, it can lead to mood swings.
Is the risk of blood clots high?
The risk is low if you are monitored correctly. We manage this by ensuring your haematocrit stays within a safe range through dosage adjustments.
Can I still have children while on TRT?
Natural fertility is usually suppressed on TRT. If you plan to have children, you should talk to your doctor about using HCG or other fertility-preserving treatments.
Does TRT cause a large prostate?
TRT can cause a slight increase in prostate size, but this is usually not clinically significant unless you already have severe symptoms of an enlarged prostate.
Will my acne go away?
Yes, acne is often a temporary side effect that occurs during the initial adjustment phase. It can usually be managed with over the counter treatments or skin hygiene.
How often do I need blood tests?
In 2026, the standard is every 3 to 6 months during the first year of therapy and then every 6 to 12 months once you are stable.
Authority Snapshot
This article was written by the MyPatientAdvice clinical team and reviewed by Dr. Stefan Petrov, a UK trained physician with an MBBS and extensive experience in general medicine, surgery, anaesthesia, ophthalmology, and emergency care. Dr. Petrov has postgraduate certifications including Basic Life Support (BLS), Advanced Cardiac Life Support (ACLS), and the UK Medical Licensing Assessment (PLAB 1 & 2). He has worked in both hospital wards and intensive care units, performing diagnostic and therapeutic procedures, and has contributed to medical education by creating patient focused health content and teaching clinical skills to junior doctors.
