A 24-year-old woman with polycystic ovary syndrome is prescribed spironolactone for hirsutism. The antiandrogenic basis of its benefit is:

• A Irreversible inhibition of adrenal CYP17
• B Stimulation of hepatic SHBG production only
• C Agonism at progesterone receptors suppressing LH
• D Inhibition of 5-alpha reductase and blockade of the androgen receptor ✓

Explanation

Spironolactone acts at two points relevant to androgen excess: it competitively blocks the androgen receptor and it inhibits steroidogenic enzymes including 5-alpha reductase, reducing local DHT formation in hair follicles. Clinical improvement in hirsutism takes several months because terminal hairs cycle slowly. Its mineralocorticoid receptor antagonism explains the accompanying risks of hyperkalemia and menstrual irregularity. It does not act as a progesterone agonist and its CYP17 inhibition is reversible and clinically minor.

Reference: Katzung Basic and Clinical Pharmacology, 15th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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