What is the most appropriate birth‑control method for a reproductive‑age woman with premenstrual dysphoric disorder (PMDD)?

Birth Control for PMDD Symptoms

For women with PMDD who desire contraception, prescribe drospirenone 3 mg/ethinyl estradiol 20 mcg in a 24/4-day regimen (24 active pills followed by 4 placebo pills), as this is the only FDA-approved contraceptive specifically indicated for treating PMDD symptoms. 1

First-Line Recommendation: Drospirenone-Containing Combined Oral Contraceptives

Drospirenone 3 mg/ethinyl estradiol 20 mcg (24/4 regimen) is FDA-approved for treating PMDD symptoms in women who choose oral contraceptives for contraception. 1 This formulation has demonstrated significant improvement in both emotional and physical PMDD symptoms in randomized, double-blind, placebo-controlled trials. 2, 3

Why This Specific Formulation Works

• Drospirenone is a spironolactone derivative with anti-mineralocorticoid and anti-androgenic properties, which distinguishes it from other progestins and contributes to its efficacy in PMDD. 1, 4
• The 24/4 regimen (24 active hormone days, 4 placebo days) shortens the hormone-free interval, which is critical because PMDD symptoms are triggered by progesterone exposure after ovulation and resolve with menstruation. 2, 5
• Studies show significant improvements in productivity, social activities, and relationships compared to placebo, with standardized mean differences of -0.31 to -0.30 for functional impairment measures. 3

Evidence Quality and Magnitude of Benefit

The evidence shows that drospirenone/ethinyl estradiol may improve overall premenstrual symptoms with a standardized mean difference of -0.41 (95% CI -0.59 to -0.24), representing a small to moderate effect size. 3 Response rates improve from 36% with placebo to 39-58% with active treatment. 3

Important caveat: Placebo effects are substantial in PMDD trials, so counseling should set realistic expectations about symptom improvement. 3, 4

Alternative Combined Hormonal Contraceptive Options

If drospirenone-containing pills are unavailable or contraindicated:

• Consider other monophasic, extended-cycle combined oral contraceptives with less androgenic progestins (such as norgestimate or desogestrel), though these lack specific PMDD efficacy data. 2
• Extended or continuous regimens that minimize hormone-free intervals may help conditions exacerbated cyclically, including PMDD-like symptoms. 6
• Start with 30-35 mcg ethinyl estradiol formulations with levonorgestrel or norgestimate as standard low-dose options. 6

Contraceptive Methods to AVOID in PMDD

Progestin-only methods have the potential to worsen mood symptoms in women with PMDD and should be avoided or used with extreme caution:

• Progestin-only pills, levonorgestrel IUD, etonorgestrel implant, and depot medroxyprogesterone acetate (DMPA) can negatively affect mood in women with baseline mood disorders including PMDD. 2
• If a patient with PMDD insists on progestin-only methods, provide careful counseling about mood worsening and arrange close follow-up. 2

Non-Hormonal Option

• Copper IUDs are recommended for women with PMDD who do not want hormonal contraception, as they provide highly effective contraception without hormonal effects on mood. 2
• However, copper IUDs do not treat PMDD symptoms and may worsen menstrual bleeding, which could be problematic if heavy bleeding is part of the symptom complex. 2

Contraindications to Drospirenone-Containing Pills

Do not prescribe drospirenone/ethinyl estradiol to women with:

• Renal impairment or adrenal insufficiency, as drospirenone has anti-mineralocorticoid activity that can cause hyperkalemia. 1
• High risk of arterial or venous thrombotic disease, including women over 35 who smoke. 1
• Uncontrolled hypertension (≥160/100 mm Hg), migraines with aura, current/history of thromboembolism, liver disease, or breast cancer. 1
• Co-administration with hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir with or without dasabuvir. 1

Monitoring and Safety Considerations

• Check serum potassium during the first treatment cycle if the patient takes medications that may increase potassium (ACE inhibitors, ARBs, potassium-sparing diuretics, NSAIDs, heparin). 1
• Monitor blood pressure regularly, as this is the primary safety requirement for long-term combined oral contraceptive use. 6
• Counsel patients that withdrawal due to adverse effects is higher with drospirenone/ethinyl estradiol (6-16%) compared to placebo (3%), with increased risks of breast pain, nausea, intermenstrual bleeding, and menstrual disorders. 3

Initiation Protocol

• Start drospirenone/ethinyl estradiol on the first day of menstrual bleeding or use "quick start" (same-day initiation) if reasonably certain the patient is not pregnant. 7, 6
• If started more than 5 days after menstrual bleeding began, use backup contraception for 7 days. 7, 6
• Take one tablet daily at the same time each day in the order directed on the blister pack. 1

Common Pitfall to Avoid

Do not prescribe standard 21/7 regimen combined oral contraceptives for PMDD, as the longer hormone-free interval may allow more luteal-phase symptoms to emerge. The 24/4 regimen is specifically designed to minimize symptom recurrence during the placebo week. 2, 5