🧬💪 Testosterone

Testosterone is the principal male androgen, essential for sexual development, muscle mass, bone density, mood regulation, and metabolic health. It is primarily produced by Leydig cells in the testes under stimulation from luteinising hormone (LH). In clinical practice, interpreting testosterone requires an understanding of circadian variation, binding proteins, and laboratory-specific reference ranges. Both underdiagnosis and overtreatment remain important concerns in UK and US healthcare systems.

⚙️ Physiology and Regulation

Testosterone secretion is controlled by the hypothalamic–pituitary–gonadal (HPG) axis. Gonadotropin-releasing hormone (GnRH) stimulates pituitary LH and FSH release, with LH driving testicular testosterone production. Circulating testosterone exerts negative feedback on both hypothalamus and pituitary. Around 60–70% is bound to SHBG, 20–30% to albumin, and only 1–3% circulates as biologically active free testosterone.

📊 Normal Testosterone Levels (UK vs US)

🔄 Conversion: 1 nmol/L ≈ 28.8 ng/dL

🧠 Interpretation Note

UK laboratories typically report in nmol/L, while US laboratories use ng/dL. Reference ranges vary between laboratories depending on assay methods and population sampling. Diagnosis should never rely on a single borderline result and must be correlated with symptoms. Morning sampling (before 11 am) is essential due to diurnal variation.

⚠️ Causes of Low Testosterone (Hypogonadism)

• 🟢 Primary (Testicular Failure)
  • Klinefelter syndrome
  • Orchitis, trauma, chemotherapy
  • Testicular torsion or surgery
• 🔵 Secondary (Central / Hypogonadotropic)
  • Pituitary tumours
  • Hyperprolactinaemia
  • Chronic opioid use
  • Obesity and metabolic syndrome
• 🟠 Functional / Age-related
  • Late-onset hypogonadism
  • Chronic illness
  • Excessive alcohol use

🔍 Clinical Features of Testosterone Deficiency

• Reduced libido and erectile dysfunction
• Fatigue and low energy
• Depressed mood and irritability
• Loss of muscle mass and strength
• Increased visceral fat
• Osteopenia and fracture risk
• Infertility

🧪 Investigation Strategy

• Two early-morning total testosterone samples
• SHBG measurement if borderline results
• Calculated or measured free testosterone
• LH and FSH (primary vs secondary)
• Prolactin if central cause suspected
• Ferritin (haemochromatosis)
• Pituitary MRI if indicated

💊 Testosterone Replacement Therapy (TRT)

• 📋 Indications
  • Consistent biochemical deficiency
  • Compatible clinical symptoms
• 💉 Preparations
  • Topical gels (first-line in UK)
  • Long-acting IM injections
  • Short-acting injections
  • Transdermal patches
• ⚠️ Monitoring
  • PSA and prostate assessment
  • Haematocrit (polycythaemia risk)
  • Lipid profile
  • Liver function

🏥 UK vs US Practice Differences

• 🇬🇧 UK: More conservative prescribing (NICE/Endocrine Society guidance)
• 🇬🇧 UK: Emphasis on confirmed deficiency + symptoms
• 🇺🇸 US: Higher rates of TRT prescribing
• 🇺🇸 US: Greater use of private clinics and “anti-ageing” services
• ⚠️ Both: Risk of overtreatment in age-related decline

🚨 Contraindications to TRT

• Prostate or breast cancer
• Untreated severe sleep apnoea
• Polycythaemia (Hct >54%)
• Uncontrolled heart failure
• Active fertility planning

📚 Key Learning Points

Testosterone must be interpreted in clinical context, not in isolation. Borderline results are common and often reflect obesity, illness, or SHBG variation rather than true hypogonadism. In UK practice, treatment is reserved for symptomatic men with confirmed biochemical deficiency. A mechanistic understanding of the HPG axis helps clinicians distinguish reversible suppression from irreversible gonadal failure.