Testosterone Replacement 

Hypogonadism is a condition resulting from the failure of the testes to produce physiological levels of Testosterone (T), the principal androgen in males. Low T levels can lead to physical and psychological symptoms. This can be down to failure of the testes to produce T (primary), or failure in hormonal stimulation of the testes, with a defect at the hypothalamic-pituitary axis (secondary). Low T levels can also be ‘functional’, most commonly relating to an elevated body mass index (BMI) or diabetes. T concentrations exhibit significant diurnal variations and can be suppressed by food intake. Acute illness or new medications can also affect T production. Which is why T levels should be taken fasted between 8-10am when well. T is principally bound to sex hormone binding globulin (SHBG) (44%) and weakly to albumin (54%), only a small fraction (0.3-3%) circulates free or active.

Diagnosis

Total T level lower than 8 nmol/L based on 2 separate fasted levels (from 8 to 10 AM) usually requires T replacement therapy. Consideration can be given to treatment if the T level is between 8-12nmol/l, where there is a definite underlying testicular or pituitary pathology and patient is symptomatic. Free T can be calculated, with a value <225pmol/L (0.225nmol/L) confirming hypogonadism. Only treat if low levels and symptomatic (any one symptom/sign). Do not test if acutely unwell. 

Main symptoms:

• mood swings and irritability

• Sexual

• loss of muscle mass and reduced ability to exercise

• fat redistribution, such as developing a large belly or "man boobs" (gynaecomastia)

• a general lack of enthusiasm or energy

• difficulty sleeping (insomnia) or increased tiredness

• poor concentration and short-term memory

T replacement will turn off the body’s natural production of testosterone. This natural production from the testes is vital for sperm production. Any form of external T replacement will render the patient infertile while on treatment. Most will return to normal sperm production on cessation, but this will take time and in a small percentage may not recover. Men seeking to start a family should avoid testosterone replacement. 

Treatment comes in two forms:

Injection

The long-acting intra-muscular depot T injection, Nebido (testosterone undeconoate) 1000mg/4ml, is administered into the gluteal muscle via a slow and deep intramuscular injection over four to five minutes. Injections are performed every 10-14 weeks once established (initially two injections 6-weeks apart).

Topical

T gels are applied on bare skin in areas with good muscle and fat coverage avoiding bony areas. Recommended areas shown below (figure 1) including shoulders or abdomen. The gel is applied in the morning over a large area and allowed to dry for 3-4 mins before dressing. Washing and bathing should be undertaken before applying the gel to avoid it being washed off. The gel will diffuse into the skin over two hours and from the skin into the body over the whole day. After the gel has been applied hands need to be washed thoroughly to avoid passive transfer to others. Caution with skin to skin contact with others, especially children and pregnant women.  Peak T seen two hours post-application. Side effects include skin irritation that could affect compliance. 

Figure1. Skin areas best to apply gels, avoiding hair prone areas for best absorption.

T therapy alone is not enough. Replacement therapy should be done in combination with regular exercise, good sleep and a balanced diet for maximal results.

Monitoring

Careful monitoring is required for men on T replacement to check for unwanted side effects. It can cause excess production of red blood cells leading to an increased risk of clots. It can also cause liver damage, and in men with undiagnosed/aggressive prostate cancer can worsen the disease. As such careful monitoring is required lifelong.

Regular blood tests listed below are required:

• T, Aim for a trough target TT level of 10-15 nmol/L
• Monitor haematocrit
• Monitor liver function
• Men aged > 50years assess prostate using PSA and DRE before commencing TT replacement and at interval checks.