What is the latest evidence on the safety and efficacy of Yaz (drospirenone and ethinyl estradiol) and Yasmin (drospirenone and ethinyl estradiol)?

Latest Evidence on Yaz and Yasmin

Yaz and Yasmin (drospirenone-containing oral contraceptives) carry a significantly elevated risk of venous thromboembolism—approximately 50-80% higher than levonorgestrel-containing pills—and should be reserved for women who specifically benefit from drospirenone's unique antimineralocorticoid properties (blood pressure reduction, PMDD treatment, acne management) and who have no VTE risk factors. 1, 2

Thrombotic Risk Profile

The most critical safety concern with drospirenone-containing contraceptives is their elevated thrombotic risk:

• VTE incidence is approximately 10 per 10,000 woman-years with drospirenone formulations, compared to 3-9 per 10,000 woman-years for standard combined oral contraceptives and 1-5 per 10,000 woman-years for non-users 1, 2

• The hazard ratio for VTE is 1.77 (95% CI 1.33-2.35) compared to low-dose estrogen comparators 2

• A UK nested case-control study found a threefold higher risk (OR 3.3,95% CI 1.4-7.6) of non-fatal idiopathic VTE with drospirenone versus levonorgestrel 3

• The relative risk of venous thrombosis is 50-80% higher than levonorgestrel-containing pills 1, 2

Blood Pressure Effects (Unique Benefit)

Unlike other oral contraceptives, drospirenone's antimineralocorticoid properties may actually lower blood pressure:

• SBP decreases of 1-4 mmHg have been demonstrated with ethinyl estradiol/drospirenone combinations 1

• In women with baseline SBP ≥130 mmHg, drospirenone 4 mg as a progestin-only pill produces SBP reductions of 8 mmHg and DBP reductions of 5 mmHg 1

• One Turkish study showed mean SBP decreased from 109.2 mmHg to 103.4 mmHg after 12 months of use 1

Efficacy for Approved Indications

Contraception

• Pearl indices of 0-0.71 demonstrate highly effective pregnancy prevention comparable to other combined oral contraceptives 4, 5

Acne Treatment

• Significant reductions in inflammatory, non-inflammatory, and total acne lesions compared to placebo in moderate acne vulgaris 1
• FDA-approved specifically for moderate acne in women who also desire contraception 1, 4

PMDD Treatment

• Yaz (24/4 regimen) is the only hormonally-based contraceptive with large randomized controlled trials demonstrating PMDD efficacy 6
• Significantly improves emotional and physical symptoms associated with PMDD over three treatment cycles 4

Cardiovascular Risk Stratification

Myocardial Infarction

• MI risk is strongly associated with cigarette smoking, diabetes, and hypertension 1
• WHO states no increased MI risk in healthy, normotensive, nondiabetic nonsmokers at any age 1

Stroke

• Increased risk of both ischemic and hemorrhagic stroke, particularly with cigarette smoking, hypertension, and age ≥35 years 1
• One Israeli study found drospirenone-containing pills were not associated with increased TIA or stroke risk 1

Absolute Contraindications

Drospirenone formulations are absolutely contraindicated in: 7

• History of deep vein thrombosis or pulmonary embolism
• Renal impairment (any degree)
• Hepatic disease
• Uncontrolled hypertension
• Smoking in women over 35 years
• History of breast cancer or other estrogen/progestin-sensitive cancers

Clinical Decision Algorithm

Choose drospirenone-containing pills when:

1. Patient specifically needs blood pressure reduction AND desires oral contraception 1
2. Patient has PMDD requiring treatment AND desires contraception 6, 4
3. Patient has moderate acne AND desires contraception 1
4. AND patient has NO VTE risk factors (no personal/family history, non-smoker, BMI <30, no thrombophilia) 1, 2

Choose levonorgestrel-containing pills when:

• Patient has any VTE risk factors 3
• Patient does not specifically need drospirenone's unique properties 1, 2
• Patient prioritizes lowest possible thrombotic risk 2, 3

Monitoring Requirements

• Serum potassium monitoring in patients with CLcr 30-49 mL/min or those on potassium-sparing drugs (though use is contraindicated in renal impairment) 7
• Blood pressure monitoring at baseline and follow-up visits 1
• Assess for VTE symptoms (leg pain, chest pain, dyspnea) at each visit 1

Common Pitfalls to Avoid

• Do not prescribe to women with any degree of renal impairment—DRSP exposure increases 37% with CLcr 30-49 mL/min 7
• Do not assume all "newer generation" pills are equivalent—drospirenone has distinctly higher VTE risk than levonorgestrel 1, 2, 3
• Do not overlook smoking status—the combination of smoking and drospirenone substantially increases cardiovascular risk 1
• Do not prescribe for acne or PMDD alone—FDA approval requires concurrent need for contraception 1, 4