How to manage Premenstrual Dysphoric Disorder (PMDD) in patients undergoing Menopausal Hormone Therapy (MHT)?

Management of Premenstrual Dysphoric Disorder (PMDD) in Patients on Menopausal Hormone Therapy (MHT)

For patients with PMDD who are undergoing MHT, selective serotonin reuptake inhibitors (SSRIs) are the first-line treatment option, with fluoxetine 10-20 mg/day being particularly effective when administered during the luteal phase of the menstrual cycle. 1, 2

Assessment and Diagnosis

• Evaluate for disruptive symptoms affecting quality of life, including mood disturbances, irritability, anxiety, and physical symptoms that occur during the luteal phase of the menstrual cycle 1
• Laboratory evaluation should include estradiol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin, as clinically indicated 3
• Rule out other medical causes of symptoms such as thyroid disease and diabetes 3
• Note that FSH is not a reliable marker of menopausal status in women on MHT 3

Pharmacological Management

First-Line Treatment: SSRIs

• SSRIs have demonstrated effectiveness in reducing premenstrual emotional and physical symptoms 4, 1

• Recommended SSRI options:

  • Fluoxetine 10-20 mg/day 2
  • Sertraline 50-150 mg/day 2
  • Escitalopram 10-20 mg/day 2
  • Paroxetine 12.5-25 mg/day 2

• Administration options:

  • Luteal phase dosing (from ovulation to menses) - effective for most patients 4, 5
  • Continuous daily dosing - may provide greater symptom reduction for severe cases 1

Important Considerations with SSRIs and MHT

• Avoid paroxetine and fluoxetine in patients on tamoxifen (if part of MHT regimen) due to CYP2D6 inhibition 3
• Prefer citalopram, escitalopram, sertraline, or venlafaxine which have minimal effect on tamoxifen metabolism 3
• Monitor for side effects including nausea, insomnia, sexual dysfunction, fatigue, dizziness, and dry mouth 1

Non-Pharmacological Approaches

• Cognitive Behavioral Therapy (CBT) has shown positive results in reducing functional impact of PMDD 2
• CBT can help reduce:
  • Depressed mood and feelings of hopelessness
  • Anxiety and mood swings
  • Irritability and conflict with others
  • Impact of symptoms on daily life 2

Special Considerations for MHT

• MHT formulations should be tailored based on menopausal symptoms and PMDD presentation:

  • For women with intact uterus: combination estrogen and progestin 3
  • For women without uterus: estrogen alone 3

• Avoid MHT in women with:

  • History of hormone-dependent cancers
  • History of abnormal vaginal bleeding
  • Active liver disease 3

• For women with severe vasomotor symptoms and PMDD, consider:

  • Adjusting MHT dosing with specialist consultation 3
  • Adding non-hormonal treatments for hot flashes such as venlafaxine if SSRIs are not sufficient 3

Monitoring and Follow-up

• Regular assessment of symptom response using validated tools 2
• Monitor for adverse effects of both SSRI therapy and MHT 1
• Consider specialist referral for complex cases or when symptoms are refractory to initial management 3

Contraindications and Cautions

• Combined estrogen plus progestin hormone therapy should not be initiated to prevent cardiovascular disease 3
• Use caution with MHT in women with history of or risk factors for cardiovascular disease 3
• Consider antiphospholipid antibody status before initiating MHT 3
• For patients with breast cancer history, avoid systemic MHT and consider non-hormonal options for both PMDD and menopausal symptoms 3