Oral Contraceptives for PMDD and Premenstrual Anxiety
Drospirenone-containing oral contraceptives (specifically drospirenone 3 mg/ethinyl estradiol 20 mcg in a 24/4 regimen) are the recommended choice for treating PMDD and premenstrual anxiety in women who also desire contraception. 1, 2
Specific Formulation and Dosing
Drospirenone 3 mg combined with ethinyl estradiol 20 mcg, administered in a 24/4 regimen (24 days of active pills followed by 4 days of placebo), is FDA-approved specifically for PMDD treatment. 1 This extended active pill regimen (24/4 rather than the traditional 21/7) provides superior symptom control by shortening the hormone-free interval when symptoms typically worsen. 3, 4
Evidence of Efficacy
Drospirenone/EE reduces overall premenstrual symptoms with a standardized mean difference of -0.41 compared to placebo, representing a small to moderate effect size 2
Response rates (≥50% symptom reduction) reach 48-62% with drospirenone/EE versus 32-36% with placebo, yielding a number-needed-to-treat of 8 patients 2, 4
Symptom improvement occurs rapidly—within the first treatment cycle—and continues through subsequent cycles 5
All three major symptom clusters improve significantly: negative emotions/mood (mean difference -3.9), physical symptoms including water retention (mean difference -2.1), and behavioral symptoms including food cravings (mean difference -1.5) 4, 5
Mechanism of Action
Drospirenone is unique among progestins as a spironolactone analogue with anti-mineralocorticoid and anti-androgenic properties 6, 7. These properties specifically address premenstrual water retention, bloating, and mood symptoms through aldosterone antagonism. 8, 1
Critical Safety Considerations and Contraindications
Absolute Contraindications
Do not prescribe drospirenone-containing OCPs if the patient has:
- Kidney, liver, or adrenal disease (risk of hyperkalemia and serious cardiac complications) 1
- Smoking and age >35 years (increased cardiovascular risk including death from MI, stroke, or blood clots) 1
- Positive antiphospholipid antibodies (estrogen increases thrombosis risk) 6
- Migraine with aura (increased stroke risk regardless of menstrual association) 6
Medication Interactions Requiring Monitoring
Check potassium levels during the first month if the patient takes any of the following chronically: 1
- NSAIDs (ibuprofen, naproxen) for arthritis or chronic pain
- Potassium-sparing diuretics (spironolactone)
- ACE inhibitors or angiotensin-II receptor blockers
- Aldosterone antagonists
- Heparin
Common Adverse Effects
Drospirenone/EE increases withdrawal rates due to adverse effects (OR 3.41) and total adverse effects (OR 2.31) compared to placebo. 2 Specifically, it increases breast pain, nausea, intermenstrual bleeding, and menstrual disorders. 2 Most adverse effects occur in the first few cycles and typically resolve. 7
Clinical Decision Algorithm
For women with PMDD or premenstrual anxiety:
First, confirm the diagnosis requires prospective symptom charting (not retrospective recall) showing symptoms that significantly interfere with work, school, social activities, or relationships 1
If the patient desires contraception AND has PMDD, prescribe drospirenone 3 mg/EE 20 mcg in 24/4 regimen 1, 2
If the patient has only PMS (less severe symptoms) without desire for contraception, do not prescribe OCPs—use alternative therapies 1
Screen for all contraindications before prescribing, particularly renal/hepatic/adrenal disease, smoking status if age >35, antiphospholipid antibodies, and migraine with aura 6, 1
Assess blood pressure before initiation, as estrogen-containing contraceptives can elevate BP 6, 8
Evaluate response after 3 cycles using validated symptom scales, as maximal benefit occurs within the first cycle and continues through subsequent cycles 5
Important Clinical Pitfalls
Do not prescribe drospirenone/EE solely for PMDD treatment if the patient does not want contraception—other medical therapies exist without the cardiovascular and thrombotic risks of combined hormonal contraceptives. 1 The FDA approval is specifically for women who choose to use oral contraceptives for birth control AND have PMDD.
Do not assume all combined oral contraceptives are equivalent for PMDD—only drospirenone-containing formulations have demonstrated efficacy for premenstrual symptoms, likely due to the unique anti-mineralocorticoid properties. 6, 2, 7 Other progestins lack this mechanism.
Do not use the traditional 21/7 regimen—the 24/4 regimen with shortened hormone-free interval is essential for PMDD symptom control, as symptoms worsen during the hormone-free days. 3, 4