Androgen replacement has been indicated in patients with symptomatic hypogonadism having confirmed two low early morning testosterone and considering the underlying cause.

Oral replacement is not generally recommended due to very poor absorption. Standard therapy is IM injection of testosterone.

Monitoring

• Prostate-specific antigen (PSA): PSA should be measured at the start of therapy and annually thereafter. If PSA is increasing over time then a referral to urology and stopping testosterone supplementation should be considered.
• Full blood count: FBC should be performed and treatment reduced or stopped if polycythaemia or haematocrit is greater than 50%.

Androgens

Testosterone intramuscular injection (IM)

(Testosterone propionate/ testosterone phenylpropionate/ testosterone isocaproate/ testosterone decanoate)

• Sustanon 250 solution for injection 250mg/1ml (£2.45 = 1ml amp)

Indications

• Male hypogonadism

Dose

• Usual therapy is 250mg IM injection every 3-4 weeks.
• For patients who report large swings in their symptomatic response, an alternative dosing schedule of a lower dose more frequently, may be given

Notes

1. Contains arachis oil and is contraindicated in patients allergic to peanuts or soya

The following second line treatment options cost considerably more and should be reserved for those patients with very fluctuant symptoms on Sustanon or those unable to attend frequent injection appointments. Transdermal preparations may be useful for patients with needle phobia.

Testosterone intramuscular injection (IM) (long-acting)

(Testosterone undecanoate)

• Nebido oily solution for injection 1000mg/4ml (£87.11 = 4ml vial)

Indications

• Male hypogonadism

Dose

• 1g every 10-14 weeks, to be given over 2 minutes by deep intramuscular injection. A second dose maybe given after 6 weeks to achieve rapid steady state plasma testosterone levels and then every 10-14 weeks

Testosterone transdermal gel

• Testogel gel 16.2mg/g (£31.11 = 88g pump)
  • One pump actuation delivers 1.25g gel containing 20.25mg testosterone
• Testogel gel 40.5mg/2.5g (£31.11 = 30 x 2.5g sachets)
  • One 2.5g sachet contains 40.5mg testosterone
• Tostran gel 2% (£28.63 = 60g pump)
  • One pump actuation delivers 0.5g gel containing 10mg testosterone

Indications

• Male hypogonadism

Dose

• Testogel 16.2mg/g pump:
  • Apply 40.5mg (two actuations) once each morning. Increase dose in steps of 20.25mg (one actuation), according to response; max 81mg (4 actuations) per day
• Testogel 40.5mg/2.5g sachet:
  • Apply 40.5mg (1 x 2.5g sachet) once each morning. Increase dose in half sachet steps (1.25g of gel) according to response; max 81mg (2 x 2.5g sachet) per day
• Tostran 2% pump:
  • Apply 60mg (six actuations) once each morning. Adjust dose according to response; max 80mg (eight actuations) per day

Notes

1. Avoid skin contact with gel application sites to prevent testosterone transfer to other people, especially pregnant women and children—consult product literature and see note 4.
2. Refer to individual product literature for specific application directions
3. Do not apply to the genital areas
4. MHRA Drug Safety Update (January 2023): Topical testosterone: risk of harm to children following accidental exposure
   1. Inform patients that accidental transfer to other people can lead to increased blood testosterone levels in the other person.
   2. Advise patients of the possible effects should accidental exposure occur in adult women (facial and/or body hair growth, deepening of voice, changes in menstrual cycle) or children (genital enlargement and premature puberty, including development of pubic hair).
   3. Counsel patients on methods to reduce the risks of accidental exposure, including washing their hands with soap and water after application, covering the application site with clean clothing (such as a t-shirt) once the gel has dried, and washing the application area with soap and water before physical contact with another person.

Anti-androgens

Cyproterone acetate

• Tablets 50mg, 100mg (£132.57 = 300mg daily)

Notes

1. Hepatotoxicity: Direct hepatic toxicity including jaundice, hepatitis and hepatic failure has been reported (usually after several months) in patients treated with cyproterone acetate 200-300mg daily. Liver function tests should be performed before treatment and whenever symptoms suggestive of hepatotoxicity occur-if confirmed cyproterone should normally be withdrawn. Cyproterone is no longer recommended for long term use
2. Prevention of tumour flare in patients starting treatment with gonadorelin analogues should be achieved by the use of cyproterone 300mg daily in 2 or 3 divided doses starting at least 3 days before the gonadorelin analogue and continuing for 3 weeks.
3. Megestrol acetate 160mg daily (see 8.3.2) or cyproterone acetate 50-150mg daily may be used in low doses to control unacceptable symptomatic flushes associated with LHRH analogues

5 alpha-reductase inhibitors

Sexual dysfunction (decreased libido, ejaculation disorder, and impotence) and breast tenderness are reported in the first year of use for fewer than one in 10 men. Advise patients:

• Sexual dysfunction tends to improve with duration of treatment.
• Changes in breast tissue (lumps, pain, nipple discharge) should be promptly reported; cases of breast cancer have (rarely) been reported.

Finasteride

• Tablets 5mg (£1.38 = 28 tablets)

Indications and dose

• Benign prostatic hyperplasia:
  • 5mg once daily

Notes

1. Finasteride can decrease PSA levels by approximately 50%. For men undergoing PSA monitoring: Recheck PSA levels after 6 months of treatment to establish a new PSA baseline. Any confirmed increase in PSA (even if values are within normal range) may indicate prostate cancer; careful interpretation is advised (see NICE CKS LUTS in men for further details).
2. Finasteride can be absorbed through the skin and is excreted in semen; women of childbearing potential should avoid handling crushed or broken finasteride tablets; use of a condom is recommended if sexual partner is pregnant or likely to become pregnant.
3. MHRA Drug Safety Update (April 2024): Finasteride: reminder of the risk of psychiatric side effects and of sexual side effects (which may persist after discontinuation of treatment)
   1. Finasteride has been associated with depression, suicidal thoughts and sexual dysfunction.
      1. 281 UK reports of finasteride and psychiatric dysfunction (depressed mood disorders, suicidal and self-injurious behaviours) and 426 UK reports of finasteride and sexual dysfunction (erectile dysfunction, decreased sex drive) were received from 1992 to 2024.
   2. Before prescribing finasteride, ask patients if they have a history of depression or suicidal ideation.
   3. Advise patients prescribed finasteride 5mg (Proscar) for benign prostatic hyperplasia to consult their doctor for further medical advice as soon as possible if they develop depression or suicidal thoughts
   4. Monitor patients for psychiatric and sexual side effects
   5. Refer to the Drug Safety Update for advice to give to patients