Combined Oral Contraceptive with Diuretic Effect
Drospirenone-containing combined oral contraceptives (such as drospirenone 3 mg/ethinyl estradiol 20-30 mcg) are the only COCs with diuretic (antimineralocorticoid) activity.
Mechanism of Diuretic Action
Drospirenone is structurally derived from 17α-spironolactone and possesses antimineralocorticoid properties nearly identical to natural progesterone. 1, 2
Drospirenone acts as an aldosterone antagonist at the mineralocorticoid receptor, promoting sodium excretion (natriuresis) and preventing fluid retention. 2, 3
At the 3 mg dose used for contraception, drospirenone induces mild natriuresis followed by compensatory increases in plasma renin activity and aldosterone levels—similar to the physiologic response to a low-sodium diet. 3, 4
This antimineralocorticoid effect directly counteracts the sodium-retaining properties of ethinyl estradiol, which stimulates hepatic angiotensinogen production and activates the renin-angiotensin-aldosterone system. 5, 3
Clinical Effects on Blood Pressure and Weight
Drospirenone-containing COCs lower systolic blood pressure by 1–4 mm Hg in normotensive women; in women with baseline systolic BP ≥130 mm Hg, the reduction averages approximately 8 mm Hg. 1, 6
One 12-month study documented mean systolic BP decreasing from 109.2 to 103.4 mm Hg with drospirenone/ethinyl estradiol use. 1
Body weight remains stable or decreases slightly with drospirenone formulations, in contrast to traditional COCs that may cause weight gain due to estrogen-induced fluid retention. 2, 4
Comparison to Other Progestins
All conventional synthetic progestogens—whether derived from 17α-hydroxyprogesterone or 19-nortestosterone (including levonorgestrel, norgestimate, desogestrel)—lack antimineralocorticoid activity and cannot counteract estrogen-induced sodium retention. 2, 3
In head-to-head studies, drospirenone 3 mg/ethinyl estradiol 30 mcg produced markedly greater increases in plasma renin activity and aldosterone compared to desogestrel 150 mcg/ethinyl estradiol 30 mcg, confirming the unique antimineralocorticoid effect of drospirenone. 4
Hyperkalemia Risk and Monitoring
Despite its potassium-sparing diuretic properties, large retrospective cohort studies show no increased risk of hyperkalemia in healthy women taking drospirenone-containing COCs compared to other oral contraceptives. 1, 7
A matched cohort study of 22,429 drospirenone initiators versus 44,858 other OC users found identical rates of hyperkalemia and related clinical outcomes (rate ratio 0.9,95% CI 0.7–1.1). 7
Serum potassium monitoring is required only during the first treatment cycle in women concurrently taking potassium-increasing medications (ACE inhibitors, ARBs, potassium-sparing diuretics, NSAIDs, heparin). 1
Routine potassium monitoring is unnecessary in women without these risk factors. 1
Clinical Selection Guidance
When hypertension, fluid retention, or blood pressure concerns are present, drospirenone-containing COCs (15–30 mcg ethinyl estradiol + 3 mg drospirenone) are the preferred formulation. 6
Drospirenone formulations are particularly suitable for individuals with borderline hypertension or premenstrual fluid retention symptoms. 6, 8
Available formulations include drospirenone 3 mg/ethinyl estradiol 30 mcg (Yasmin) and drospirenone 3 mg/ethinyl estradiol 20 mcg in a 24/4 regimen (Vestura, YAZ). 1, 8
Important Caveat on VTE Risk
Drospirenone-containing COCs carry a 50–80% higher venous thromboembolism risk compared to levonorgestrel-containing pills (approximately 10 events per 10,000 woman-years versus 6 per 10,000). 1
This elevated VTE risk is attributed specifically to the drospirenone component and must be weighed against the cardiovascular benefits of blood pressure reduction. 1
Standard VTE contraindications apply: age ≥35 years with smoking, prior VTE, thrombophilia, prolonged immobilization, or severe uncontrolled hypertension. 1