Male hypogonadism (Guidelines)

If history is suggestive, biochemical evaluation is as per the flowchart below to determine if testosterone levels are below the normal reference range.

• In general, testosterone levels <6 mmol/L are more common in secondary causes of hypogonadism, whereas milder degrees of testosterone deficiency may be more suggestive of non-gonadal illness / late onset hypogonadism associated with increasing age and obesity.
• Opiate medications may also be implicated in some.

Abbreviations:

• FSH: follicle stimulating hormone          
• LH: luteinising hormone         
• NGI: Non-gonadal illness

Mild testosterone deficiency and suspected non-gonadal illness:

• Lifestyle measures and weight loss should be encouraged as 5 to 10% weight loss may improve testosterone concentrations.

Testosterone replacement

In general, testosterone replacement will be recommended by endocrinology in cases of obvious hypogonadism eg Klinefelter’s syndrome, hypopituitarism. In more borderline cases a 3 to 6 month trial of treatment may be considered after counselling patients on the potential benefits and risks of treatment. 

• In brief, the long term risks and cardiovascular safety are unknown, and whilst treatment has not been shown to cause prostate cancer, testosterone may promote its growth.
• It may also exacerbate or unmask symptoms of benign prostatic hyperplasia.
• Some studies have shown an increased risk of venous thromboembolism, AF and fractures, albeit the latter may not be a direct effect given the early onset.
• There is no guarantee erectile dysfunction will improve.

Absolute contraindications:

• Desire for fertility
• Current prostate carcinoma
• Breast carcinoma
• Raised haematocrit >0.50
• Elevated PSA or prostate lump on digital rectal examination that has not been evaluated
• NYHA grade 3 or 4 heart failure
• Liver tumour
• Hypercalcaemia
• Nephrotic syndrome.

Screening for prostate cancer

The UK Society for Endocrinology guidance does NOT suggest routinely screening for prostate cancer (with PSA and digital rectal examination) during testosterone treatment. However, we would usually check a baseline PSA and monitor men aged >45 years and in higher risk individuals eg black ethnicity, or individuals with a first degree relative with prostate cancer aged <60. 

Medications:

See Highland Formulary: Testosterone and esters (Formulary: Endocrine)

Gels

Base product choice on patient preference and availability. 

Tostran^® 2% gel

• One metered application contains 10 mg of testosterone
• Manufacturer advises apply gel on clean, dry, intact skin of abdomen or both inner thighs, preferably in the morning. Gently rub in with a finger until dry before dressing. Wash hands with soap and water after applying gel; avoid washing application site for at least 2 hours. Not to be applied on genital area.
• Dose:
  • Apply 4 applications (40 mg) once daily, subsequent application adjusted according to response (To note that this dose is lower than the BNF starting dose of 60mg)
  • Usual maintenance dose: 4 applications (40 mg) per day
  • Maximum: 8 applications (80 mg) per day.

Testogel^® 16.2 mg/g gel sachet

• One 2.5g sachet contains 40.5 mg of testosterone.
• Apply thin layer of gel on clean, dry, healthy skin over right and left upper arms and shoulders immediately after sachet is opened. Not to be applied on genital area as high alcohol content may cause local irritation. Allow to dry for 3 to 5 minutes before dressing. Wash hands with soap and water after applying gel, and cover the site with clothing once gel dried; avoid shower or bath for at least 1 hour.
• Dose:
  • Apply the contents of 1 sachet (40.5 mg) once daily; adjusted in steps of 20.25 mg, dose to be adjusted according to response
  • Usual standard dose: 1 sachet (40.5 mg) per day
  • Maximum: 2 sachets (81 mg) per day.

Testogel^® 16.2 mg/g gel pump

• One pump actuation delivers 1.25 g of gel containing 20.25 mg of testosterone.
• Apply thin layer of gel on clean, dry, healthy skin over right and left upper arms and shoulders. Not to be applied on genital area as high alcohol content may cause local irritation. Allow to dry for 3 to 5 minutes before dressing. Wash hands with soap and water after applying gel, and cover the site with clothing once gel dried; avoid shower or bath for at least 2 hours.
• Dose:
  • Apply 2 actuations (40.5 mg) once daily; increased in steps of 20.25 mg, adjusted according to response.
  • Usual maintenance dose: 2 actuations per day (40.5mg)
  • Maximum: up to 4 actuations per day (81 mg).

Notes: 

• Check testosterone levels 2 to 6 hours after applying the gel in the morning
  • Adjusting dose, aiming for middle of reference range.
  • If >30 nmol/L a dose reduction will be required (NB possible skin contamination).  
• Applied daily in the morning as per manufacturer’s instructions.
• Wash hands after application and avoid skin to skin contact for 6 hours.
• Can be discontinued quickly.

Injection

Testosterone undecanoate (Nebido^®) 1 g/4 mL (250 mg/ mL) solution for injection

• Dose: 1g by deep IM (gluteal) injection over 2 minutes
• The first two injections are given 6 weeks apart, to achieve rapid stead state plasma testosterone levels then ~12 weekly.
• Aim for trough testosterone levels just below, or at the lower end of the normal reference range prior to the third injection.
• Adjust injections to 10 to 14 weekly. Occasionally a longer interval is needed.  

Monitoring

FBC, PSA (where applicable), lipids, and LFTs should be checked prior to commencing testosterone replacement.

• Repeat at 3, 6, and 12 months, and then annually thereafter.
• It is important to monitor the haematocrit in particular, to avoid polycythaemia.

• FBC: full blood count
• IM: intramuscular 
• LFT: liver function test
• NYHA: New York Heart Association
• PSA: prostate specific antigen