Not all women can or wish to take hormone therapy. Here are the alternatives with the best evidence.

Fezolinetant (Veozah) — first-in-class NK3 antagonist:

  • FDA-approved specifically for hot flashes (May 2023)
  • SKYLIGHT 1 & 2 phase 3 trials (The Lancet, 2023): 45 mg daily significantly reduced VMS frequency vs placebo at weeks 4 and 12
  • ~50-60% reduction in hot flush frequency (compared to ~20-66% placebo response in nonhormone trials)
  • Improvement within 1 week, sustained over 52 weeks in extension studies
  • Most common side effect: headache. Rare, reversible liver enzyme elevation — periodic monitoring recommended

SSRIs/SNRIs (proven off-label):

  • Paroxetine: 40-65% reduction (FDA-approved as Brisdelle 7.5 mg)
  • Venlafaxine/desvenlafaxine: 40-60% reduction, best for night sweats
  • Escitalopram and citalopram also effective
  • MsFLASH trial (Joffe et al., JAMA Internal Medicine 2014, n=339): low-dose venlafaxine 75 mg reduced VMS by 47.6% vs 28.6% placebo

Gabapentin and pregabalin:

  • Gabapentin: 40-60% reduction, best for night sweats; start 300 mg at bedtime
  • Side effects: drowsiness, headache

Cognitive Behavioral Therapy (CBT):

  • Level I evidence for reducing hot flash bother and improving sleep (The Menopause Society 2023, NICE 2026)
  • Does NOT reduce frequency but significantly reduces how much they bother you
  • Clinical hypnosis also Level I evidence

Lifestyle:

  • Avoid triggers (coffee, alcohol, spicy food) — frequency not changed but bother can decrease
  • Paced respiration at onset of a flash
  • Cooling strategies: fans, layered clothing, cold drinks

Important context from research:

Placebo response in nonhormone VMS trials ranges from 20% to 66% — women with higher anxiety show greater placebo response. This does NOT make the effect 'not real'; it underscores the role of mind-body approaches.

⚠️ Dietary supplements (soy, black cohosh, evening primrose, vitamin E, cannabinoids) are NOT recommended by The Menopause Society due to lack of rigorous evidence. A 2024 evidence map identified 57 RCTs of complementary therapies but methods were too varied for conclusions.