How do combined oral contraceptives (COCs) help regulate menstrual-related mood disorders?

Combined Oral Contraceptives for Menstrual-Related Mood Disorders

Combined oral contraceptives (COCs) do NOT effectively regulate menstrual-related mood disorders and should not be used as primary treatment for premenstrual dysphoric disorder (PMDD) or severe premenstrual syndrome. 1

Why COCs Are Not Recommended for Mood Regulation

COCs create a false hormonal environment without addressing the underlying pathophysiology of menstrual-related mood disorders. 1 The key problems include:

• COCs do not restore spontaneous menses or normalize the metabolic factors that contribute to mood symptoms - they simply create an exogenous ovarian steroid environment that provides a false sense of security when withdrawal bleeding occurs 1

• The mechanism of PMDD involves abnormal responses to normal hormonal fluctuations, particularly involving progesterone metabolites and neurotransmitters like serotonin and GABA 2 - COCs suppress these natural fluctuations but do not correct the underlying neurobiological sensitivity

• There is limited and inconsistent evidence that COCs improve mood symptoms in women with PMDD 1

Evidence-Based First-Line Treatment for PMDD

Selective serotonin reuptake inhibitors (SSRIs) are the established first-line treatment for premenstrual dysphoric disorder, not COCs. 3, 4, 5, 6

SSRI Dosing Recommendations:

• Sertraline 50-150 mg/day 3
• Fluoxetine 10-20 mg/day 3
• Escitalopram 10-20 mg/day 3
• Paroxetine 12.5-25 mg/day 3

SSRI Administration Options:

• SSRIs can be taken either continuously (daily) or intermittently (luteal phase only) with similar effectiveness 5, 6
• Luteal phase dosing (only during the 2 weeks before menstruation) is unique to PMDD treatment and distinguishes it from depression management 6
• The moderate effect size for symptom reduction is SMD -0.65 (95% CI -0.46 to -0.84) for end scores 5

Common SSRI Side Effects (Number Needed to Harm):

• Nausea (NNH = 7) 5
• Decreased energy/asthenia (NNH = 9) 5
• Somnolence (NNH = 13) 5
• Fatigue (NNH = 14) 5
• Decreased libido (NNH = 14) 5

Limited Role for Specific COC Formulations

Only one specific COC formulation has FDA approval for PMDD: drospirenone 3 mg with ethinyl estradiol 20 mcg in a 24+4 day regimen. 3, 2

• This formulation may be considered as first or second-line treatment depending on individual circumstances 3
• The beneficial effect may relate to drospirenone's antimineralocorticoid and antiandrogenic properties rather than standard hormonal contraceptive effects 2
• It remains unclear whether the benefit is due to the specific progestogen, estrogen type, or the extended 24-day hormonal regimen 2

Adjunctive Treatments

Cognitive behavioral therapy (CBT) shows positive results in reducing functional impairment, depressed mood, anxiety, mood swings, irritability, and symptom severity in PMDD. 3

• CBT could potentially become first-line treatment if more high-quality evidence emerges 3
• Current evidence supports CBT as an effective adjunct to pharmacological treatment 3

Critical Clinical Pitfalls

Do not prescribe standard COCs to women seeking treatment for PMDD with the expectation of mood improvement - this creates false reassurance and delays appropriate treatment 1

Distinguish PMDD from premenstrual syndrome (PMS) - they have different symptom severity, potentially different etiologies, and require different treatment approaches 3

Ensure prospective symptom tracking for at least 2 menstrual cycles before diagnosing PMDD - symptoms must be present only during the luteal phase and significantly impair functioning 4, 6

Consider comorbid conditions - psychotropic medications may be beneficial for treating anxiety, depression, and obsessive-compulsive behaviors that coexist with menstrual symptoms 1