ANTI-ANDROGENIC DRUGS

• MOA: Acts by inhibiting synthesis, activation or action of androgens.

Drug groups:

I) Steroid synthesis inhibitors:

• Drugs included: Ketoconazole & Abiraterone.

Ia) Ketoconazole:

MOA:

• Inhibits synthesis of adrenal & gonadal hormones.
• On prolonged use – Serious toxicity limits usage in treatment of prostatic carcinoma.

Adverse effects:

• Cause gynaecomastia – Due to increase in estradiol:testosterone ratio.

Ib) Abiraterone:

• Orally active prodrug.

MOA: 

• Acts by inhibiting 17-α-hydroxylase & 17, 20-lyase.
• Reduces synthesis of both cortisol & androgens.
• Approved for castration-resistant refractory prostate cancer.

II) 5-α reductase inhibitors:

5-α reductase –

• Most testosterone actions are mediated by its conversion to DHT by 5-α reductase.
• Actions mediated include growth of prostate, male pattern baldness & hirsutism in females.
• Drugs: Finasteride & dutasteride.
• Uses: BHP treatment, male pattern baldness & hirsutism – By reducing DHT production.

III) Androgen receptor inhibitors:

MOA: 

• Acts as antagonists of androgen receptors.

Drugs: 

• Cyproterone, cyproterone acetate, flutamide, bicalutamide, enzalutamide, nilutamide.

Cyproterone acetate:

• Marked progestational activity.
• A component of contraceptive pills.
• Inhibits feedback enhancement of LH & FSH.

Uses: 

• Hirsutism treatment.
• Treatment of prostatic carcinoma.

Flutamide:

• Cause gynaecomastia & reversible liver damage.
• Combined with GnRH agonists (like leuprolide) – To reduce initial flare-up reaction.

IV) Aldosterone antagonist:

Spironolactone:

• Competes with DHT for its receptor.
• Used for hirsutism treatment & in heart failure.