Testosterone replacement therapy (TRT) is prescribed to men with confirmed hypogonadism to restore hormone levels and alleviate symptoms such as fatigue, reduced libido, and mood disturbances. Whilst TRT can significantly improve wellbeing in many patients, some men experience mood swings during treatment. Understanding whether low testosterone treatments cause mood swings, why these changes occur, and how to manage them is essential for anyone considering or currently receiving TRT. This article examines the relationship between testosterone therapy and mood alterations, explores the underlying mechanisms, and provides guidance on when to seek medical advice, all aligned with UK clinical practice and MHRA-approved preparations.

Understanding Low Testosterone and Its Treatment Options

Low testosterone, medically termed hypogonadism, occurs when the testes produce insufficient amounts of the hormone testosterone. This condition affects approximately 2–4% of men, with prevalence increasing with age. Testosterone plays crucial roles beyond reproductive function, influencing bone density, muscle mass, fat distribution, red blood cell production, and psychological wellbeing.

Diagnosis requires both clinical symptoms and biochemical confirmation through blood tests. The British Society for Sexual Medicine recommends measuring total testosterone levels on two separate morning occasions, ideally between 7am and 11am when levels peak naturally. Normal ranges typically fall between 10–30 nmol/L, though individual laboratory reference ranges may vary. Symptoms prompting investigation include reduced libido, erectile dysfunction, fatigue, decreased muscle mass, and mood disturbances. Additional tests including luteinising hormone (LH), follicle-stimulating hormone (FSH) and prolactin help differentiate between primary and secondary hypogonadism.

Treatment options for confirmed hypogonadism include:

• Testosterone replacement therapy (TRT) – available as gels or injections in the UK

• Lifestyle modifications – weight loss, exercise, and improved sleep can naturally boost testosterone

• Treatment of underlying conditions – addressing obesity, type 2 diabetes, or pituitary disorders

The MHRA-approved testosterone preparations in the UK include transdermal gels (such as Testogel, Testavan, and Tostran) and intramuscular injections (Nebido - testosterone undecanoate, or Sustanon - mixed testosterone esters). Each delivery method has distinct pharmacokinetic profiles affecting how testosterone levels fluctuate throughout the treatment cycle. NICE Clinical Knowledge Summary (CKS) guidance emphasises that TRT should only be initiated after thorough assessment and with ongoing monitoring of symptoms, testosterone levels, haematocrit (pausing treatment if ≥0.54), and prostate health. Treatment aims to restore testosterone to mid-normal physiological levels, thereby alleviating symptoms whilst minimising adverse effects.

It's important to note that TRT suppresses sperm production and can affect fertility. Men wishing to father children should discuss this with their healthcare provider before starting treatment.

Can Testosterone Replacement Therapy Cause Mood Swings?

Testosterone replacement therapy can indeed cause mood swings in some individuals, though the relationship between TRT and mood changes is complex and not universally experienced. According to MHRA product information, mood alterations are classified as 'common' to 'uncommon' side effects, with frequency varying between different testosterone preparations.

The nature of mood changes associated with TRT can manifest in several ways. Some men report increased irritability, aggression, or emotional lability—experiencing rapid shifts between different emotional states. Conversely, others may notice anxiety, restlessness, or paradoxically, depressive symptoms during treatment. These effects appear more commonly during the initial months of therapy as the body adjusts to altered hormone levels.

Factors influencing mood-related side effects include:

• Dosage and formulation – supraphysiological doses increase risk

• Rate of testosterone level changes – rapid fluctuations may trigger mood instability

• Pre-existing mental health conditions – history of mood disorders increases vulnerability

• Individual sensitivity – genetic and neurobiological factors affect response

It is important to distinguish between mood improvements and mood swings. Many men with hypogonadism experience low mood, irritability, and reduced wellbeing as symptoms of testosterone deficiency itself. For these individuals, appropriate TRT often improves mood stability and overall psychological functioning. However, when testosterone levels rise too quickly, exceed physiological ranges, or fluctuate significantly between doses, mood destabilisation can occur. Short-acting injectable preparations may be more likely to cause fluctuations than daily-applied gels, which provide more stable hormone levels.

Patient information from UK urological and endocrine societies notes that whilst mood enhancement is a recognised benefit of TRT in hypogonadal men, careful dose titration and monitoring remain essential to prevent adverse psychological effects.

Why Mood Changes Occur During Testosterone Treatment

The mechanisms underlying mood changes during testosterone treatment likely involve complex interactions between hormones, neurotransmitters, and brain structures regulating emotion. Research suggests testosterone may influence the central nervous system through androgen receptors located in regions including the amygdala, hippocampus, and prefrontal cortex—areas critically involved in emotional processing and regulation.

Testosterone is thought to influence several neurotransmitter systems that modulate mood. Studies suggest it may affect serotonin synthesis and receptor sensitivity, with alterations potentially contributing to irritability or depressive symptoms. The hormone may also impact dopaminergic pathways involved in motivation and reward processing, whilst potentially modulating GABAergic systems that regulate anxiety and emotional reactivity. When testosterone levels change rapidly or reach supraphysiological concentrations, these neurotransmitter systems may become temporarily dysregulated, possibly manifesting as mood instability.

Aromatisation represents another possible mechanism. Testosterone converts to oestradiol (a form of oestrogen) through the enzyme aromatase. This conversion occurs in various tissues including adipose tissue and the brain itself. Oestradiol may play roles in male mood regulation, and excessive aromatisation—particularly in men with higher body fat—can lead to elevated oestrogen levels. Both excessively high and low oestrogen have been hypothesised to contribute to mood disturbances, irritability, and emotional lability in men, though routine clinical measurement of oestradiol is not standard in UK TRT monitoring unless specifically indicated.

The pharmacokinetics of different testosterone preparations significantly influence mood stability. Injectable testosterone preparations like Sustanon produce peak levels shortly after administration, followed by gradual decline until the next injection. This creates a 'roller-coaster' effect, with some men experiencing mood elevation during peaks and irritability or low mood as levels decline. In contrast, transdermal gels such as Testogel provide more stable daily testosterone levels, potentially reducing mood fluctuations. Individual variation in testosterone metabolism, receptor sensitivity, and psychological factors further explains why mood changes affect some men but not others during treatment.

Managing Mood Swings While on Testosterone Therapy

Effective management of mood swings during testosterone therapy requires a collaborative approach between patient and healthcare provider, with strategies tailored to individual circumstances. The primary goal involves achieving stable, physiological testosterone levels whilst minimising psychological side effects.

Optimising treatment regimen represents the first-line approach:

• Dose adjustment – reducing dosage to achieve testosterone levels in the mid-normal range within your laboratory's reference range

• Changing formulation – switching from injections to daily gels for more stable levels

• Adjusting injection frequency – for short-acting preparations like Sustanon, smaller, more frequent doses may help (following product guidance)

• Timing modifications – administering treatment at consistent times to establish routine

Regular monitoring proves essential for identifying and addressing mood-related issues. NICE Clinical Knowledge Summary and the British Society for Sexual Medicine recommend assessing testosterone levels and haematocrit at 3–6 months after initiating therapy, at 12 months, then annually thereafter. However, men experiencing mood disturbances may require more frequent evaluation. Treatment should be paused or adjusted if haematocrit reaches ≥0.54. PSA and digital rectal examination should be performed according to age and risk factors.

Lifestyle interventions support mood stability during TRT:

• Regular exercise – particularly resistance training and aerobic activity

• Sleep optimisation – maintaining consistent sleep schedules and addressing sleep disorders

• Stress management – mindfulness, relaxation techniques, or cognitive behavioural strategies

• Dietary considerations – balanced nutrition supporting overall hormonal health

• Limiting alcohol – excessive consumption can exacerbate mood instability

For men with persistent mood symptoms despite optimised TRT, additional interventions may be warranted. Psychological support through counselling or cognitive behavioural therapy can help develop coping strategies for emotional regulation. In some cases, temporary discontinuation of TRT may be necessary under medical supervision to determine whether symptoms are treatment-related. The decision to continue, modify, or cease testosterone therapy should always involve careful discussion of risks and benefits between patient and clinician.

If you experience any suspected side effects from testosterone treatment, report them to the MHRA Yellow Card scheme, which helps monitor medication safety.

When to Seek Medical Advice About Mood Changes

Whilst mild mood fluctuations during the initial adjustment period of testosterone therapy may be expected, certain symptoms warrant prompt medical evaluation. Understanding when mood changes require professional assessment helps ensure patient safety and treatment optimisation.

Seek urgent medical attention if experiencing:

• Severe depression – persistent low mood, hopelessness, or suicidal thoughts

• Uncontrollable anger or aggression – particularly if leading to relationship problems or risk of harm

• Significant anxiety or panic attacks – especially if interfering with daily functioning

• Psychotic symptoms – hallucinations, delusions, or severely disorganised thinking

• Manic symptoms – markedly elevated mood, decreased need for sleep, impulsive behaviour, or grandiosity

If you're at immediate risk, call 999 or go to A&E. For urgent concerns, call NHS 111. The Samaritans (116 123) provide 24/7 emotional support.

These symptoms may indicate that testosterone levels have become excessive, that underlying psychiatric conditions have been unmasked, or that the treatment regimen requires immediate modification. In cases of severe mood disturbance, temporary cessation of TRT may be necessary under medical supervision whilst psychiatric assessment and stabilisation occur.

Contact your GP or prescribing specialist if you notice:

• Mood swings persisting beyond the first 3 months of treatment

• Progressive worsening of irritability or emotional instability

• Mood changes affecting work performance, relationships, or quality of life

• New-onset anxiety or depressive symptoms during treatment

• Personality changes noted by family members or friends

Your healthcare provider can assess whether symptoms relate to testosterone therapy, adjust treatment accordingly, and arrange appropriate investigations. Blood tests measuring testosterone and other relevant hormones help identify biochemical causes of mood disturbance. In some instances, referral to endocrinology or psychiatry services may be appropriate for specialist input.

Men with pre-existing mental health conditions require particularly careful monitoring during TRT. Inform your prescriber about any history of depression, bipolar disorder, anxiety disorders, or other psychiatric conditions before commencing treatment. Regular follow-up appointments allow early detection of mood changes and timely intervention, optimising both the safety and efficacy of testosterone replacement therapy. Never stop or adjust your testosterone treatment without consulting your healthcare provider.

Frequently Asked Questions