What are the side effects, contraindications, and warning signs associated with Yaz (drospirenone/ethinyl estradiol) combined oral contraceptive?

Yaz (Drospirenone/Ethinyl Estradiol) Side Effects and Safety Profile

Yaz carries a 50-80% higher risk of venous thromboembolism compared to levonorgestrel-containing pills and should be reserved for women who specifically need its unique antimineralocorticoid or antiandrogenic properties—such as blood pressure reduction or moderate acne treatment—and who have no VTE risk factors. 1, 2

Common Side Effects (Resolve Within 2-3 Cycles)

The majority of common adverse effects are self-limiting and rarely require discontinuation 1:

• Menstrual irregularities (breakthrough bleeding/spotting) occur in 24.9% of PMDD trial participants and 4.7% of contraception/acne trial participants, most frequently during the first 2-3 cycles 1, 3
• Nausea/vomiting affects 4.2% of users in contraception trials and 15.8% in PMDD trials 3, 2
• Headache/migraine occurs in 6.7% of contraception users and 13.0% of PMDD users 3, 2
• Breast pain/tenderness affects 4.0% of contraception users and 10.5% of PMDD users 3, 2
• Mood changes occur in 2.2% of contraception users, with specific symptoms including irritability (2.8%) and affect lability (2.1%) in PMDD trials 3, 2
• Weight gain affects 2.5% of PMDD trial participants 3
• Decreased libido occurs in 2.8% of PMDD users 3

Serious Cardiovascular Risks

Venous Thromboembolism (VTE)

The VTE risk with drospirenone is specifically attributed to the drospirenone component itself, not the estrogen dose 1:

• VTE incidence is approximately 10 per 10,000 woman-years with drospirenone formulations, compared to 6 per 10,000 woman-years for standard low-dose estrogen COCs and 2 per 10,000 woman-years in non-users 1, 2
• The hazard ratio for VTE is 1.77 (95% CI 1.33-2.35) compared to levonorgestrel-containing pills 1
• Relative risk is 50-80% higher than levonorgestrel formulations 1, 2

Arterial Thromboembolism

• The absolute attributable risk for major cardiovascular events (myocardial infarction, stroke) is approximately 2 per 10,000 person-years 1
• Risk is strongly associated with cigarette smoking, diabetes, and hypertension 1

Metabolic Effects

Blood Pressure (Unique Benefit)

Unlike other progestins, drospirenone's antimineralocorticoid activity lowers blood pressure 1, 2:

• Systolic blood pressure decreases by 1-4 mmHg in most users 1
• In women with baseline systolic BP ≥130 mmHg, systolic BP drops by approximately 8 mmHg 1
• One study showed mean systolic BP decreased from 109.2 mmHg to 103.4 mmHg over 12 months 1

Hyperkalemia Risk

• Large retrospective cohort analyses found no increased risk of hyperkalemia with drospirenone-containing COCs compared to other COCs 1, 2
• Even when combined with spironolactone (5,752 patients), hyperkalemia rates were not significantly elevated 1
• Routine serum potassium monitoring is not required in healthy women 1, 2
• However, check serum potassium during the first treatment cycle in women on long-term medications that may increase potassium (ACE inhibitors, ARBs, potassium-sparing diuretics, NSAIDs, heparin) 3, 2

Absolute Contraindications

Do not prescribe Yaz to women with 2, 3:

• History of deep vein thrombosis or pulmonary embolism 2, 3
• Renal impairment or adrenal insufficiency 2, 3
• Uncontrolled hypertension or hypertension with vascular disease 2, 3
• Smoking combined with age >35 years 2, 3
• History of breast cancer or other estrogen/progestin-sensitive malignancies 2, 3
• Active or severe liver disease (hepatitis, cirrhosis, hepatic tumors) 2, 3
• Ischemic heart disease or complicated valvular heart disease 2
• Prior cerebrovascular accident (stroke) 2
• Migraine with focal neurologic symptoms at any age, or migraine without aura in women ≥35 years 2, 3
• Undiagnosed abnormal uterine bleeding 2, 3
• Co-administration with Hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir with or without dasabuvir 3

Cancer Risk Profile (Protective)

• Combined oral contraceptives including Yaz are linked to a 29% reduction in gynecologic malignancies and net decrease in overall cancer risk 1
• Significant risk reductions for colon, uterine, and ovarian cancers 1, 2
• Overall cancer-related mortality appears lower with COC use 1

Emergency Discontinuation Criteria

Immediately stop Yaz and seek urgent medical evaluation for 1:

• Signs of stroke: sudden severe headache, visual changes, weakness, speech difficulties 1
• Signs of myocardial infarction: chest pain, jaw pain, diaphoresis 1
• New-onset migraine with aura or focal neurologic symptoms 1, 3
• Signs of deep vein thrombosis: unilateral leg pain, swelling, warmth 3
• Signs of pulmonary embolism: sudden shortness of breath, chest pain 3

Management of Common Side Effects

Breakthrough Bleeding

• Reassure patients that breakthrough bleeding typically resolves within 2-3 cycles 1
• Verify adherence to the dosing schedule, as missed pills are the primary cause of persistent bleeding 1
• If bleeding persists beyond 3 cycles, rule out pregnancy, STDs, new pathologic uterine conditions, and drug interactions before switching methods 4

Nausea

• Advise taking the pill with food or at bedtime; nausea generally resolves within the first few cycles 1

Clinical Decision Algorithm

Choose Yaz specifically when 1, 2:

• Patient needs oral contraception AND has moderate acne vulgaris (FDA-approved indication) 2, 1
• Patient needs contraception AND would benefit from modest blood pressure reduction 1
• Patient has PMDD symptoms and desires oral contraception 3, 5

Choose levonorgestrel-containing pills instead when 1:

• Patient has any VTE risk factors (personal/family history of VTE, obesity, prolonged immobilization, thrombophilia) 1
• Patient does not specifically need drospirenone's unique antimineralocorticoid or antiandrogenic properties 1

Required Monitoring

• Baseline: Blood pressure measurement, breast and pelvic examinations (including Papanicolaou smear), urine pregnancy test 2
• Ongoing: Blood pressure monitoring at follow-up visits, assessment for VTE symptoms at each visit 2, 1
• Note: Papanicolaou smear and pelvic examination are no longer mandatory before initiating COCs but provide valuable information 2

Critical Drug Interactions

• Enzyme inducers (CYP3A4 inducers including anticonvulsants, rifampin, St. John's wort, griseofulvin) may decrease effectiveness or increase breakthrough bleeding—counsel patients to use backup contraception 3, 2
• Tetracycline antibiotics do NOT reduce COC effectiveness when taken concomitantly (common misconception) 2
• Monitor potassium when combined with medications that increase serum potassium (ACE inhibitors, ARBs, NSAIDs, potassium-sparing diuretics, heparin) 2, 3

Timing Considerations

• Start no earlier than 4 weeks postpartum in women who are not breastfeeding 3
• Stop at least 4 weeks before and through 2 weeks after major surgery to reduce VTE risk 3
• Acne improvement takes time—statistically significant improvement by cycle 3, but counsel patients that visible reduction may not be appreciated for the first few months 2