Antiandrogens

Antiandrogens block androgen action or lower androgen production. They treat hirsutism, acne and hair loss in women, prostate cancer, benign prostatic hyperplasia and gender-affirming therapy.

Several drugs with different actions share the label: receptor blockers (spironolactone, cyproterone acetate, flutamide, bicalutamide, enzalutamide, apalutamide, darolutamide), enzyme inhibitors (finasteride, dutasteride, abiraterone) and gonadotropin suppressors.

Mechanism. Receptor blockers compete with testosterone and dihydrotestosterone at the androgen receptor. Finasteride and dutasteride block 5-alpha reductase and lower dihydrotestosterone. Abiraterone blocks CYP17 and reduces androgen synthesis in adrenals, testes and tumour tissue. Spironolactone also lowers androgen production and is an aldosterone antagonist.

Pharmacokinetics. Spironolactone is converted to active metabolites with half-lives of 13 to 24 hours. Cyproterone acetate has a long half-life of 2 to 4 days. Bicalutamide has a half-life of about 6 days.

Women with hirsutism. Treatment takes 6 months for visible effect. Combine an antiandrogen with effective contraception, since antiandrogens can feminise a male foetus. Mechanical hair removal helps at once.

Dose adjustment. Spironolactone starting 50 mg daily, increased every 4 to 6 weeks.

• First-line. Combined oral contraceptive for hirsutism and acne; spironolactone for acne and hirsutism when contraception is acceptable; androgen deprivation with GnRH analogue for advanced prostate cancer; finasteride for BPH with large prostate.
• Alternative. Cyproterone-containing pill; finasteride for female pattern hair loss (specialist, with contraception).
• Specialist. Enzalutamide, apalutamide, darolutamide and abiraterone in castration-resistant or metastatic disease; gender-affirming therapy (spironolactone or cyproterone).
• Emergency. None.

Selection. For women, begin with the combined pill, and add spironolactone after 6 months if response is poor. For prostate cancer, use a GnRH analogue (or orchidectomy) as the backbone, adding an antiandrogen as indicated.

Contraindications. Pregnancy (all except where specified, due to risk of feminisation of male foetus); hyperkalaemia and severe kidney disease (spironolactone); liver disease (flutamide, cyproterone); history of meningioma (cyproterone); active thrombosis (cyproterone); seizure disorder (enzalutamide, apalutamide, relative).

Serious adverse effects.

• Spironolactone: hyperkalaemia, menstrual irregularity, breast tenderness, dizziness.
• Cyproterone: liver injury, meningioma (with high dose and long use), depression, thrombosis, weight gain.
• Finasteride and dutasteride: reduced libido, erectile dysfunction, depression, gynaecomastia; PSA falls by about 50%.
• Bicalutamide and flutamide: gynaecomastia, breast pain, hot flushes, liver toxicity (flutamide).
• Enzalutamide and apalutamide: fatigue, hypertension, falls, seizures, rash; abiraterone: hypertension, hypokalaemia, fluid retention.

Major interactions. Spironolactone with ACE inhibitors, ARBs, potassium supplements and trimethoprim (hyperkalaemia); enzalutamide and apalutamide are strong CYP3A4 inducers and lower levels of many drugs (warfarin, DOACs, antiretrovirals); abiraterone with CYP2D6 substrates; CYP3A4 inhibitors raise bicalutamide and darolutamide levels slightly.

Common prescribing errors.

• Prescribing in women without contraception.
• Not checking potassium on spironolactone.
• Forgetting to double the PSA on finasteride.
• No steroid with abiraterone.
• Missing drug interactions with enzalutamide.

Special groups.

• Pregnancy: contraindicated.
• Breastfeeding: avoid.
• Children and adolescents: specialist use only.
• Older adults: monitor for falls, hypotension and cognitive effects.
• Kidney: avoid spironolactone in severe disease; monitor potassium in mild disease.
• Liver: avoid flutamide and cyproterone; reduce abiraterone in moderate disease.
• East Africa: prostate cancer is often advanced at diagnosis, so bicalutamide with GnRH analogue or orchidectomy is a realistic first step; newer androgen receptor drugs are costly; hirsutism and acne from polycystic ovary syndrome are common, and spironolactone is affordable but needs reliable contraception and potassium checks.

Monitoring. Potassium and creatinine at baseline, 4 weeks and then every 6 to 12 months (spironolactone); liver tests (cyproterone, flutamide, abiraterone); PSA and testosterone in prostate cancer; blood pressure; symptoms of mood change.

Referral and escalation. Visual change or headache with cyproterone; jaundice; hyperkalaemia; rapidly rising PSA; pregnancy.

Comparison with alternative classes. Antiandrogens treat the cause of androgen-driven skin and hair problems and prolong survival in prostate cancer, but need contraception and monitoring. Cosmetic hair removal and topical treatments are safer alternatives for mild disease.