What are the common and serious side effects of Yaz (drospirenone/ethinyl estradiol) and how should they be managed?

Yaz Side Effects and Management

Yaz (drospirenone 3mg/ethinyl estradiol 20mcg) carries common side effects including breakthrough bleeding, nausea, breast tenderness, and headaches that typically resolve within 2-3 cycles, but requires careful monitoring for serious thrombotic complications, particularly venous thromboembolism which occurs at approximately 10 per 10,000 woman-years—significantly higher than other combined oral contraceptives. 1, 2

Common Side Effects (≥2% incidence)

The most frequently reported adverse reactions from clinical trials include:

• Menstrual irregularities (24.9% in PMDD trials, 4.7% in contraception/acne trials): Primarily breakthrough bleeding and spotting, most common in first 2-3 cycles 3, 4
• Nausea/vomiting (15.8% in PMDD trials, 4.2% in contraception/acne trials) 3
• Headache/migraine (13.0% in PMDD trials, 6.7% in contraception/acne trials) 3
• Breast pain/tenderness (10.5% in PMDD trials, 4% in contraception/acne trials) 3
• Mood changes (2.2% in contraception/acne trials): Including mood swings, depression, and affect lability 3

These common side effects typically resolve spontaneously within the first 2-3 cycles of use and rarely require discontinuation. 4

Serious Adverse Effects Requiring Immediate Attention

Venous Thromboembolism (VTE) - The Primary Concern

Drospirenone-containing contraceptives carry a 50-80% higher VTE risk compared to levonorgestrel-containing pills, with an incidence of approximately 10 per 10,000 woman-years versus 6 per 10,000 for standard combined oral contraceptives. 1, 2, 4

• The hazard ratio for VTE is 1.77 (95% CI 1.33-2.35) compared to other low-dose estrogen contraceptives 1, 2
• This elevated risk is specifically attributed to the drospirenone component 4
• For context, non-users have VTE rates of approximately 2 per 10,000 person-years 4

Critical teaching point: While the relative risk is elevated, the absolute attributable risk remains low, and pregnancy itself carries higher VTE risk than Yaz use. 4

Cardiovascular and Cerebrovascular Events

• Myocardial infarction risk increases primarily in women with additional risk factors: cigarette smoking, diabetes, hypertension 2
• Stroke risk (both ischemic and hemorrhagic) increases particularly with smoking, hypertension, and age ≥35 years 2
• Healthy, normotensive, nondiabetic nonsmokers show no increased MI risk at any age 2
• The attributable risk for cardiovascular events is approximately 2 per 10,000 person-years 4

Hyperkalemia Concerns - Largely Theoretical

Despite drospirenone's antimineralocorticoid properties and structural similarity to spironolactone, multiple large retrospective cohort studies found no increased risk of hyperkalemia with drospirenone-containing contraceptives compared to other combined oral contraceptives. 4

• Even concomitant use with spironolactone (5,752 patients studied) showed no significant hyperkalemia risk 4
• Routine potassium monitoring is not required in healthy women 4

Absolute Contraindications

Yaz must not be prescribed to women with: 4, 2, 5

• History of deep vein thrombosis or pulmonary embolism
• Uncontrolled hypertension (though drospirenone may actually lower BP in controlled hypertension)
• Smoking and age >35 years
• History of breast cancer or other estrogen/progestin-sensitive cancers
• Active or severe liver disease (hepatitis, cirrhosis, liver tumors)
• Ischemic heart disease or valvular heart disease with complications
• History of cerebrovascular accident
• Migraine with focal neurologic symptoms at any age, or migraine without aura if ≥35 years

Unique Beneficial Effects

Blood Pressure Reduction

Unlike other combined oral contraceptives that may elevate blood pressure, drospirenone's antimineralocorticoid properties actually decrease blood pressure by 1-4 mmHg systolic in most users. 4, 1, 5

• One study demonstrated mean systolic BP decrease from 109.2 to 103.4 mmHg after 12 months 4, 1
• In women with baseline SBP ≥130 mmHg taking drospirenone 4mg as progestin-only pill, SBP decreased by 8 mmHg 4, 1

Cancer Risk Profile

Combined oral contraceptives, including Yaz, are associated with a net decrease in overall cancer risk, including a 29% decreased risk of gynecologic malignancies. 4

• Significantly reduced risk of colon, uterine, and ovarian cancer 4
• Conflicting data exists regarding breast cancer, but overall cancer mortality is reduced 4

Management Algorithm

Initial Prescribing Decision

Reserve Yaz specifically for women who:

• Desire oral contraception AND have moderate acne vulgaris (FDA-approved indication) 4
• Desire oral contraception AND have premenstrual dysphoric disorder 3, 6
• Would benefit from blood pressure reduction while needing contraception 4, 1

Choose alternative contraceptives (levonorgestrel-containing) when:

• Patient has any VTE risk factors 2
• Patient does not specifically need drospirenone's unique antiandrogenic or antimineralocorticoid properties 2

Monitoring Requirements

• Baseline blood pressure measurement before initiation 3
• Blood pressure check at yearly visits 3
• Assess for VTE symptoms (leg pain, swelling, chest pain, shortness of breath) at each visit 2
• No routine potassium monitoring required in healthy women 4

Managing Common Side Effects

Breakthrough bleeding (most common complaint):

• Reassure patient this typically resolves within 2-3 cycles 4, 3
• Verify medication adherence, as missed pills are the primary cause 4
• If persistent beyond 3 cycles, evaluate for other causes

Nausea:

• Recommend taking pill with food or at bedtime 3
• Typically resolves within first few cycles 4

Mood changes:

• Women with history of depression require careful observation 3
• Discontinue if depression recurs to a serious degree 3

When to Discontinue Immediately

Stop Yaz and seek emergency evaluation for: 3

• Signs/symptoms of VTE (unilateral leg swelling, chest pain, dyspnea)
• Signs/symptoms of stroke (sudden severe headache, vision changes, weakness)
• Signs/symptoms of MI (chest pain, jaw pain, diaphoresis)
• New onset migraine with aura or focal neurologic symptoms
• Jaundice or severe right upper quadrant pain (liver disease)

Discontinuation Rates

• 6.6% discontinued in contraception trials, most commonly for headache/migraine (1.6%) or nausea/vomiting (1%) 3
• 11.6% discontinued in PMDD trials, most commonly for nausea/vomiting (4.6%) or menstrual irregularity (4.2%) 3