What is the recommended combined oral contraception (COC) regimen for treating Premenstrual Dysphoric Disorder (PMDD)?

Combined Oral Contraceptive Regimen for Premenstrual Dysphoric Disorder (PMDD)

A drospirenone-containing combined oral contraceptive (COC) in a 24/4 regimen is the recommended treatment for PMDD in women seeking contraception. 1

First-Line COC Regimen for PMDD

• Drospirenone 3 mg with ethinyl estradiol 20 μg in a 24/4 regimen (24 active pills followed by 4 placebo pills) is FDA-approved specifically for PMDD treatment 1
• This regimen has demonstrated significant improvement in both emotional and physical symptoms of PMDD compared to placebo 2, 3
• The 24/4 regimen provides a shorter hormone-free interval which contributes to better symptom control compared to traditional 21/7 regimens 4, 3

Mechanism of Action for PMDD Treatment

• Drospirenone is a spironolactone-like progestin with antimineralocorticoid and antiandrogenic properties that help address PMDD symptoms 5, 6
• The extended regimen (24 active pills) minimizes hormone fluctuations that can trigger PMDD symptoms 3
• Continuous hormone delivery helps stabilize neurotransmitter systems involved in PMDD pathophysiology, including serotonin and GABA 7, 6

Clinical Considerations

• Effectiveness for PMDD has been demonstrated primarily in the first three menstrual cycles of use 1, 2
• Blood pressure monitoring is important for all COC users, especially those with PMDD who may be sensitive to fluid retention 4
• Women should be counseled that a backup method (condoms or abstinence) should be used for the first 7 days when starting the COC if initiated >5 days after the start of menses 4

Contraindications and Cautions

• COCs containing drospirenone are contraindicated in women with:
  • Renal impairment or adrenal insufficiency (due to potential hyperkalemia) 1
  • High risk of arterial or venous thrombotic disease 1
  • Uncontrolled hypertension 4, 1
  • Women over 35 who smoke 4, 1
• Drospirenone-containing COCs may be associated with a higher risk of venous thromboembolism compared to COCs containing levonorgestrel 1

Potential Side Effects

• Common side effects include:
  • Menstrual irregularities (24.9%) 1
  • Nausea (15.8%) 1
  • Headache/migraine (13%) 1
  • Breast tenderness (10.5%) 1
  • Mood changes 4, 1

Alternative Options

• If drospirenone-containing COCs are contraindicated, other monophasic COCs with less androgenic progestins may be helpful, though less well-studied 7
• For women who cannot use hormonal methods, copper IUDs are recommended as they do not affect mood symptoms 7
• Caution is advised with progestin-only methods (POP, LNG-IUD, implant, DMPA) as they may potentially worsen mood symptoms in women with PMDD 7

Clinical Pearl

• When prescribing for PMDD, always consider that COCs containing drospirenone may increase serum potassium levels due to the antimineralocorticoid activity; check serum potassium during the first treatment cycle in women on medications that may increase potassium concentration 1