What are the alternative treatment options for menopausal hot flashes in women who are contraindicated for Hormone Replacement Therapy (HRT)?

Management of Menopausal Hot Flashes in Women Contraindicated for HRT

For women contraindicated for hormone replacement therapy (HRT), first-line treatment for menopausal hot flashes should be non-hormonal pharmacologic options including SNRIs, SSRIs, gabapentin, or pregabalin. 1

First-Line Pharmacologic Options

Antidepressants

• SNRIs/SSRIs:
  • Venlafaxine (SNRI): 37.5-75 mg daily 1
  • Paroxetine: 7.5-12.5 mg daily (avoid in women taking tamoxifen) 1
  • Citalopram: Lower doses than used for depression 1
  • Desvenlafaxine: Effective for vasomotor symptoms 2

Important caution: Pure SSRIs, particularly paroxetine, should be avoided in women taking tamoxifen due to inhibition of CYP2D6, which blocks conversion of tamoxifen to active metabolites 1

Anticonvulsants

• Gabapentin: 900 mg/day (start at lower doses and titrate up) 1
  • Particularly useful when taken at bedtime due to somnolence side effect 1
  • Shown to decrease hot flash severity score by 46% compared to 15% with placebo 1
• Pregabalin: Lower doses than used for neuropathic pain 1

Other Options

• Clonidine: Antihypertensive medication with modest efficacy 1
• Oxybutynin: May help with vasomotor symptoms 3

Second-Line and Emerging Options

• Neurokinin-3 receptor antagonists (fezolinetant, elinzanetant): Newer agents with efficacy approaching that of hormone therapy 3
• Low-dose vaginal estrogen for genitourinary symptoms only (minimal systemic absorption) 4
• Ospemifene: FDA-approved for dyspareunia due to menopausal atrophy 5

Non-Pharmacologic Approaches

Lifestyle Modifications

• Dress in layers that can be removed during hot flashes 1
• Wear natural fibers 1
• Use cold packs intermittently 1
• Identify and avoid triggers using a hot flash diary (e.g., spicy foods, alcohol, caffeine, stress) 1
• Maintain healthy weight and stop smoking (hot flashes may be more severe in overweight women and smokers) 1
• Regular exercise may reduce risk or ameliorate hot flashes 1

Behavioral Interventions

• Paced respiration training: Shown to be significantly beneficial in RCTs 1
• Relaxation techniques: 20 minutes daily with proper training 1
• Clinical hypnosis: Pilot studies show 59% decrease in daily hot flashes 1

Limited Evidence Interventions

• Acupuncture: Mixed results in studies, may improve sleep quality 1
• High-dose vitamin E (800 IU/day): Limited efficacy for mild symptoms, but supplementation >400 IU/day linked with increased all-cause mortality 1

Interventions to Avoid

• Black cohosh: No benefit over placebo, reports of liver failure 1, 6
• Multibotanical supplements with soy: May worsen symptoms 1
• Evening primrose oil: Insufficient evidence of benefit, may cause nausea and headache 6

Treatment Algorithm Based on Symptom Severity

1. Mild to moderate symptoms:

   • Start with lifestyle modifications and behavioral interventions
   • If insufficient, add vitamin E (≤400 IU/day) or clonidine 1

2. Severe symptoms:

   • Start with SNRIs/SSRIs (venlafaxine preferred if on tamoxifen)
   • Review for efficacy and side effects at 2-4 weeks 1
   • If ineffective or intolerable, switch to gabapentin
   • Review at 4-6 weeks 1

3. For persistent symptoms despite above measures:

   • Consider referral to specialist for discussion of other options

Special Considerations

• Women with breast cancer: Carefully weigh risks and benefits; non-hormonal options are strongly preferred 1, 7
• Women on tamoxifen: Avoid paroxetine and other strong CYP2D6 inhibitors; venlafaxine is preferred 1, 2
• Women with sleep disturbances: Consider gabapentin at bedtime to leverage somnolence side effect 1

Regular follow-up is essential to assess treatment efficacy and manage side effects. Review treatment at 2-4 weeks for antidepressants and 4-6 weeks for gabapentin 1.