Tools for Practice Outils pour la pratique

#353 – Turn Down the Heat! Can non-hormonal drugs improve vasomotor symptoms in menopause?

Do non-hormonal medications improve menopausal vasomotor symptoms?

After 12 weeks, approximately 50-75% of women with menopausal vasomotor symptoms experience ≥50% decrease in hot flashes with selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs) or gabapentin versus 35-60% on placebo. Placebo reduces the number of hot flashes by about 40-50%, with an additional 10-20% reduction from SSRIs, SNRIs, and gabapentin.

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  • All results statistically different unless indicated.
  • SSRIs (six meta-analyses, 4-11 RCTs, 547-2069 patients);1-6 SNRIs (five meta-analyses, 2-7 RCTs, 301-3685 patients);2-3,5,7-8 gabapentin (five meta-analyses, 2-9 RCTs, 901-3519 patients);2,3,9-11 clonidine (one meta-analysis, 4 RCTs, 30-198 patients).3 When outcomes not available, largest RCTs for each drug class retrieved.
    • Hot flashes (daily):
      • SSRIs,1 gabapentin,desvenlafaxine:12-13 Baseline 9-11;
        • Mean difference: 1-2 fewer hot flashes over placebo at 4-12 weeks.
        • Example: 3-4 hot flashes (desvenlafaxine) versus 5-6 (placebo).12
      • Oxybutynin (148 patients):14 Four fewer hot flashes over placebo.
      • Clonidine:One fewer hot flash over placebo.
        • No difference when breast cancer patients excluded.
    • Proportion with ≥50% reduction in number of hot flashes. Examples at 12 weeks, (unless noted):
      • Gabapentin15 (600 patients): 73% versus 60% (placebo), number needed to treat (NNT)=8.
      • Desvenlafaxine12 (567 patients): 68-75% versus 48% (placebo), NNT=4-5.
      • SSRIs:
        • Paroxetine16 (614 patients) or escitalopram17 (205 patients): 48-55% versus 36% (placebo), NNT=6-9 over 8-12 weeks.
        • Fluoxetine, citalopram (150 patients):18 No difference versus placebo.
    • Global assessment: “Much/Very much improved” over 12 weeks:
      • Gabapentin:15 58% versus 44% (placebo), NNT=8.
      • Oxybutynin:14 73% versus 26% (placebo), NNT=2.
    • Quality of life: Versus placebo:
      • Citalopram, fluoxetine, or sertraline:18-19 No difference.
      • Escitalopram:20 Not clinically different.
  • Limitations: Event rates not reported;2-8,10-11 standard mean differences used (difficult to interpret clinically);1,2,8,10-11 breast cancer patients included;2,3,6,9-11 RCTs industry funded.13-16,18-19

  • Guidelines:
    • First-line: Hormone therapy; second-line: SSRIs, SNRIs, or gabapentin.21
  • Hormone therapy:
    • Versus placebo: ~18 fewer hot flashes/week (mostly estradiol 1-2mg).22
    • Versus gabapentin: 1 fewer hot flash/day with hormone therapy.10
    • Versus venlafaxine: RCT underpowered to compare agents for efficacy outcomes.23
      • Patient satisfaction: 70% versus 51% venlafaxine.
  • Dosing (daily):21 Paroxetine 10-25mg, desvenlafaxine 100-150mg, gabapentin 900-2400mg.

Waguih Tannous November 27, 2023

Interesting but not conclusive results.

Dubravka Rakic November 28, 2023


Luc Chagnon November 30, 2023

HRT should be gold standard , we should stop to have concern about HRT with bioidentical drugs

DATONYE DOUGLAS December 10, 2023

Excellent study material

Sayema Parveen December 11, 2023

i do use venlafaxine in my practice with good results

Nonyelum Agomo December 12, 2023

Alternatives to HRT are always welcome

James Livingstone February 5, 2024

Given a 50% respone rate to placebo therapy, it seems reasonable to start with such therapy for those
patients who inclined to more natural products as first ;ine therapy.

Lionel Martinez June 21, 2024

Interesting to see how HRT is still prominent but there is still such hesitation to taking it

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  • Ashley Domingues PharmD Candidate
  • Émélie Braschi MD PhD
  • Samantha S. Moe PharmD

1. Shams T, Firwana B, Habib F, et al. J Gen Intern Med. 2014; 29(1):204-213.

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16. Simon JA, Portman DJ, Kaunitz AM, et al. Menopause. 2013; 20(10):1027-35.

17. Freeman EW, Guthrie KA, Caan B, et al. JAMA. 2011; 305(3): 267-74.

18. Suvanto-Luukkonen E, Koivunen R, Undstrom H, et al. Menopause. 2005; 12(1): 18-26.

19. Gordon PR, Kerwin JP, Boesen KG, et al. Menopause. 2006; 13(4): 568-75.

20. LaCroix AZ, Freeman EW, Larson J, et al. Maturitas. 2012; 73(4): 361-8.

21. The North American Menopause Society. Menopause. 2023; 30(6):573-590.

22. MacLennan AH, Broadbent JL, Lester S, et al. Cochrane Database Syst Rev. 2004; Issue 4,Art. No: CD002978.

23. Joffe H, Guthrie KA, LaCroix AZ, et al. JAMA. Intern Med 2014; 174(7): 1058-66.

Authors do not have any conflicts of interest to declare