A woman is prescribed combined oral contraceptive pills and notices that her blood pressure rises after 3 months. The mechanism responsible is:

• A Progestogen component activates mineralocorticoid receptors causing sodium retention
• B Both estrogen and progestogen increase adrenal cortisol production
• C Ethinyl estradiol directly activates vascular alpha-1 adrenergic receptors causing vasoconstriction
• D Estrogen component stimulates hepatic angiotensinogen production, increasing renin-angiotensin system activity and aldosterone levels ✓

Explanation

Synthetic estrogens in combined OCPs (especially ethinyl estradiol) stimulate hepatic synthesis of angiotensinogen (renin substrate). The resultant increase in angiotensinogen raises angiotensin I and II generation, increasing aldosterone secretion, sodium and water retention, and blood pressure. This is a class effect of estrogen-containing contraceptives and is the major mechanism of OCP-induced hypertension. Blood pressure elevation is typically modest (3-5 mmHg) but can be more pronounced in susceptible women. Progestogens with androgenic activity may contribute slightly, but the predominant mechanism is estrogen-mediated angiotensinogen induction.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

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