What are the treatment options for Premenstrual Dysphoric Disorder (PMDD) using combined oral contraceptives with a higher dose of estrogen than 0.02 mg of ethinyl estradiol (EE)?

Combined Oral Contraceptives for PMDD with Higher Estrogen Doses

For PMDD treatment, use drospirenone 3 mg plus ethinyl estradiol 30 μg (not 20 μg) if you specifically want a higher estrogen dose than 0.02 mg, though the FDA-approved formulation for PMDD contains only 20 μg ethinyl estradiol. 1

FDA-Approved Treatment

The only FDA-approved combined oral contraceptive for PMDD is drospirenone 3 mg plus ethinyl estradiol 20 μg in a 24+4-day regimen 1, 2. This formulation is specifically indicated for treating PMDD symptoms in women who choose oral contraceptives for contraception 1.

Higher Estrogen Dose Options

If you require a formulation with more than 0.02 mg (20 μg) ethinyl estradiol:

• Drospirenone 3 mg plus ethinyl estradiol 30 μg is available and has been studied for PMDD, though it lacks FDA approval for this specific indication 3, 4
• The 30 μg formulation showed improvement in premenstrual symptoms in clinical trials, though data are more limited than for the 20 μg formulation 3
• One trial comparing the 30 μg drospirenone formulation to desogestrel 150 μg plus ethinyl estradiol 30 μg showed similar premenstrual symptom control over two years 5

Evidence Quality and Efficacy

The 20 μg ethinyl estradiol formulation has the strongest evidence base:

• Two placebo-controlled trials demonstrated significantly reduced PMDD symptom severity after three months (mean difference -7.92; 95% CI -11.16 to -4.67) 5
• Greater improvements occurred in productivity impairment, social activities, and relationships compared to placebo 5
• The initial trial showed statistically significant improvement only in appetite, acne, and food cravings (p = 0.027), though trends favored treatment across all 22 symptom items 3

The 30 μg formulation has weaker evidence:

• One small trial showed numerical improvement in PMDD symptoms but with limited data for analysis 5
• Studies of the 30 μg formulation for less severe premenstrual symptoms provided insufficient data on primary outcomes 5

Critical Safety Considerations

Common adverse effects with drospirenone-containing contraceptives include:

• Intermenstrual bleeding (odds ratio 4.92; 95% CI 3.03 to 7.96) 5
• Nausea (odds ratio 3.15; 95% CI 1.90 to 5.22) 5
• Breast pain (odds ratio 2.67; 95% CI 1.50 to 4.78) 5
• Overall treatment-related adverse events are more likely than placebo (odds ratio 2.36; 95% CI 1.62 to 3.44) 5

Absolute contraindications for estrogen-containing contraceptives:

• High thromboembolism risk including cyanotic heart disease, Fontan physiology, mechanical valves, prior thrombotic events, or pulmonary arterial hypertension 6
• Women with cardiovascular risk factors should avoid estrogen-containing formulations 6

Important Caveats

• The effectiveness of drospirenone/ethinyl estradiol for PMDD beyond three menstrual cycles has not been established 1
• PMDD diagnosis requires DSM-IV criteria with prospective symptom assessment over at least two menstrual cycles before treatment 1
• This treatment is only indicated for women who desire oral contraception; it should not be prescribed solely for PMDD if contraception is not needed 1
• Low-dose combined oral contraceptives (≤20 μg ethinyl estradiol) are preferred when estrogen-containing contraceptives are appropriate, to minimize thrombotic risk 6

Clinical Bottom Line

While you asked about higher estrogen doses, the 20 μg ethinyl estradiol formulation has superior evidence for PMDD treatment and lower cardiovascular risk 5, 6. If you specifically require >20 μg ethinyl estradiol for other clinical reasons, the 30 μg drospirenone formulation is available but represents off-label use for PMDD with less robust efficacy data 3, 5.