Commentary| Volume 40, ISSUE 10, P1778-1786, October 2018

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Beyond Estrogen: Treatment Options for Hot Flashes

Published:September 12, 2018DOI:


      Nonhormonal medications and complementary and alternative therapies are used by many women seeking relief from bothersome hot flashes. However, health care professionals may be less familiar with these treatment modalities. Although estrogen remains the most effective medication to reduce hot flashes, its potential harmful effects have led investigators to examine other treatments for hot flashes, and many women seek alternative forms of relief. Most of these trials are limited by a significant placebo effect, which frequently equals the effectiveness of the medication being evaluated. Despite this limitation, selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), and gabapentin have robust evidence for hot flash reduction. Each of these may be chosen for additional treatment effects that may benefit some women. Complementary and alternative medication trials are fraught with additional limitations, namely, a large placebo effect, greater homogeneity of participants, lack of validated tools, and lack of robust reporting of adverse effects. The data appear most robust for isoflavone supplementation, with overall hot flash reduction similar to the SSRIs, SNRIs, and gabapentin. Mindfulness-based stress reduction therapy also has evidence of effectiveness and may be an ideal choice for some. Primrose oil, Chinese herbal medicine, acupuncture, and yoga have mixed results. The concerns related to hepatotoxicity preclude the use of black cohosh. Exercise, relaxation, and paced respiration have no proven benefit thus far in reducing hot flashes. Our goal with this commentary is to arm clinicians with information about the medications and complementary therapies available to provide symptom relief to women. Providing information about the possible benefits and harms of these therapies despite the limitations of the current evidence is helpful to patients and can help guide them to seek the treatment option most beneficial and appealing to them.

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        • Kronenberg F.
        • Downey J.A.
        Thermoregulatory physiology of menopausal hot flashes: a review.
        Canadian Journal of Physiology and Pharmacology. June 1987; 65: 1312-1324
        • Kronenberg Fredi
        Menopausal hot flashes: a review of physiology and biosociocultural perspective on methods of assessment.
        Journal of Nutrition. July 2010; 140: 1380S-1385S
        • Grant MarkD.
        • Marbella Anne
        • Wang AmyT.
        • Pines Elizabeth
        • Hoag Jessica
        • Bonnell Claudia
        • Ziegler KathleenM.
        • Aronson Naomi
        Menopausal Symptoms: Comparative Effectiveness of Therapies.
        Agency for Healthcare Research and Quality (US), RockvilleMD2015
        • Writing group for THE WOMEN'S HEALTH INITIATIVE
        Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial.
        JAMA. 2002; 288 (July): 321-333
        • KEENAN NoraL.
        • MARK Saralyn
        • FUGH-BERMAN Adriane
        • BROWNE Doris
        • KACZMARCZYK Joseph
        • HUNTER Carrie
        Severity of menopausal symptoms and use of both conventional and complementary/alternative therapies.
        Menopause. 2003; 10 (November): 507-515
        • LI Lujin
        • XU Ling
        • WU Junyi
        • DONG Lidan
        • LV Yinghua
        • ZHENG Qingshan
        Quantitative analysis of placebo response and factors associated with menopausal hot flashes.
        Menopause. 2017; 24 (August): 932-937
        • LOPRINZI CharlesL.
        • SLOAN Jeff
        • STEARNS Vered
        • SLACK Rebecca
        • IYENGAR Malini
        • DIEKMANN Brent
        • KIMMICK Gretchen
        • LOVATO James
        • GORDON Paul
        • PANDYA Kishan
        • GUTTUSO Jr, Thomas
        • BARTON Debra
        • NOVOTNY Paul
        Newer antidepressants and gabapentin for hot flashes: an individual patient pooled analysis.
        Journal of Clinical Oncology. 2009; 27 (June): 2831-2837
        • STEARNS Vered
        • BEEBE KatherineL.
        • IYENGAR Malini
        • DUBE Eric
        Paroxetine controlled release in the treatment of menopausal hot flashes: a randomized controlled trial.
        JAMA. 2003; 289 (June): 2827-2834
        • GRADY Deborah
        • COHEN Beth
        • TICE Jeffrey
        • KRISTOF Margaret
        • OLYAIE Azin
        • SAWAYA GeorgeF
        Ineffectiveness of sertraline for treatment of menopausal hot flushes: a randomized controlled trial.
        Obstetrics and Gynecology. 2007; 109 (April): 823-830
        • SHAMS Taghreed
        • FIRWANA Belal
        • HABIB Farida
        • ALSHAHRANI Abeer
        • ALNOUH Badria
        • MURAD MohammadHassan
        • FERWANA Mazen
        SSRIs for hot flashes: a systematic review and meta-analysis of randomized trials.
        Journal of General Internal Medicine. 2014; 29 (January): 204-213
        • SIMON JamesA.
        • PORTMAN DavidJ.
        • KAUNITZ AndrewM.
        • MEKONNEN Hana
        • KAZEMPOUR Kazem
        • BHASKAR Sailaja
        • LIPPMAN Joel
        Low-dose paroxetine 7.5 mg for menopausal vasomotor symptoms: two randomized controlled trials.
        Menopause. 2013; 20 (October): 1027-1035
        • CARROLL DanaG.
        • LISENBY KatelinM.
        • CARTER TracyL
        Critical appraisal of paroxetine for the treatment of vasomotor symptoms.
        International Journal of Women's Health. 2015; 7 (June): 615-624
        • POLLACK Andrew
        F.D.A. Panel Advises Against Two Medicines to Treat Hot Flashes.
        (The New York Times [online]. 4 March[Accessed 24 November 2017]. Available from:)
        • POLLACK Andrew
        F.D.A. Approves a Drug for Hot Flashes.
        (The New York Times [online]. 28 June[Accessed 24 November 2017]. Available from:)
        • GUTTUSO Jr, Thomas
        • KURLAN Roger
        • MCDERMOTT MichaelP
        • KIEBURTZ Karl
        Gabapentin's effects on hot flashes in postmenopausal women: a randomized controlled trial.
        Obstetrics and Gynecology. 2003; 101 (February): 337-345
        • BUTT DebraA.
        • LOCK Michael
        • LEWIS JacquelineE.
        • ROSS Sue
        • MOINEDDIN Rahim
        Gabapentin for the treatment of menopausal hot flashes: a randomized controlled trial.
        Menopause. 2008; 15 (March): 310-318
        • SAADATI Najmieh
        • MOHAMMADJAFARI Razieh
        • NATANJ Solmaz
        • ABEDI Parvin
        The effect of gabapentin on intensity and duration of hot flashes in postmenopausal women: a randomized controlled trial.
        Global Journal of Health Science. 2013; 5 (September): 126-130
        • LOPRINZI CharlesL.
        • QIN Rui
        • BALCUEVA ErnieP.
        • BACLUEVA ErnieP.
        • FLYNN KathleenA.
        • ROWLAND Jr, KendrithM.
        • GRAHAM DavidL.
        • ERWIN NancyK.
        • DAKHIL ShakerR.
        • JURGENS DonaldJ.
        • BURGER KelliN.
        Phase III, randomized, double-blind, placebo-controlled evaluation of pregabalin for alleviating hot flashes, N07C1.
        Journal of Clinical Oncology. 2010; 28 (February): 641-647
        • SETCHELL K.D.
        • CASSIDY A.
        Dietary isoflavones: biological effects and relevance to human health.
        Journal of Nutrition. 1999; 129 (March): 758S-767S
        • LETHABY Anne
        • MARJORIBANKS Jane
        • KRONENBERG Fredi
        • ROBERTS Helen
        • EDEN John
        • BROWN Julie
        Phytoestrogens for menopausal vasomotor symptoms.
        Cochrane Database of Systematic Reviews. 2013; (December)CD001395
        • MYERS S.P.
        • VIGAR V.
        Effects of a standardised extract of Trifolium pratense (Promensil) at a dosage of 80mg in the treatment of menopausal hot flushes: A systematic review and meta-analysis.
        Phytomedicine. 2017; 24 (January): 141-147
        • LEACH MatthewJ.
        • MOORE Vivienne
        Black cohosh (Cimicifuga spp.) for menopausal symptoms.
        Cochrane Database of Systematic Reviews. 2012; (September)CD007244
        • MAHADY GailB.
        • LOW DOG
        • Tieraona BARRETT
        • Marilyn L.
        • CHAVEZ MaryL.
        • GARDINER Paula
        • KO Richard
        • MARLES RobinJ.
        • PELLICORE LindaS.
        • GIANCASPRO GabrielI.
        • SARMA DandapantulaN
        United States Pharmacopeia review of the black cohosh case reports of hepatotoxicity.
        Menopause. 2008; 15 (July): 628-638
        • ZHU Xiaoshu
        • LIEW Yuklan
        • LIU ZhaoLan
        Chinese herbal medicine for menopausal symptoms.
        Cochrane Database of Systematic Reviews. 2016; 3 (March)CD009023
        • GREEN Julia
        • DENHAM Alison
        • INGRAM Jennifer
        • HAWKEY Sue
        • GREENWOOD Rosemary
        Treatment of menopausal symptoms by qualified herbal practitioners: a prospective, randomized controlled trial.
        Family Practice. 2007; 24 (October): 468-474
        • FARZANEH Farah
        • FATEHI Setareh
        • SOHRABI Mohammad-Reza
        • ALIZADEH Kamyab
        The effect of oral evening primrose oil on menopausal hot flashes: a randomized clinical trial.
        Archives of Gynecology and Obstetrics. 2013; 288 (November): 1075-1079
        • DE LUCA A.CasteloBranco
        • DA FONSECA A.Maggio
        • LOPES C.M.Carvalho
        • BAGNOLI V.R.
        • SOARES J.M.
        • BARACAT E.C.
        Acupuncture-ameliorated menopausal symptoms: single-blind, placebo-controlled, randomized trial.
        Climacteric. 2011; 14 (February): 140-145
        • AVIS NancyE.
        • COEYTAUX RemyR.
        • ISOM Scott
        • PREVETTE Kristen
        • MORGAN Timothy
        Acupuncture in Menopause (AIM) study: a pragmatic, randomized controlled trial.
        Menopause. 2016; 23 (June): 626-637
        • NIR Yael
        • HUANG MaryI.
        • SCHNYER Rosa
        • CHEN Bertha
        • MANBER Rachel
        Acupuncture for postmenopausal hot flashes.
        Maturitas. 2007; 56 (April): 383-395
        • DODIN Sylvie
        • BLANCHET Claudine
        • MARC Isabelle
        • ERNST Edzard
        • WU Taixiang
        • VAILLANCOURT Caroline
        • PAQUETTE Joalee
        • MAUNSELL Elizabeth
        Acupuncture for menopausal hot flushes.
        Cochrane Database of Systematic Review. 2013; (July)CD007410
        • CHIU Hsiao-Yean
        • PAN Chieh-Hsin
        • SHYU Yuh-Kae
        • HAN Bor-Cheng
        • TSAI Pei-Shan
        Effects of acupuncture on menopause-related symptoms and quality of life in women in natural menopause: a meta-analysis of randomized controlled trials.
        Menopause. 2015; 22 (February): 234-244
        • NEWTON KatherineM.
        • REED SusanD.
        • GUTHRIE KatherineA.
        • SHERMAN KarenJ.
        • BOOTH-LAFORCE Cathryn
        • CAAN Bette
        • STERNFELD Barbara
        • CARPENTER JanetS.
        • LEARMAN LeeA.
        • FREEMAN EllenW.
        • COHEN LeeS.
        • JOFFE Hadine
        • ANDERSON GarnetL.
        • LARSON JosephC.
        • HUNT JulieR.
        • ENSRUD KristineE.
        • LACROIX AndreaZ.
        Efficacy of yoga for vasomotor symptoms: a randomized controlled trial.
        Menopause. 2014; 21 (April): 339-346
        • LEE MyeongSoo
        • KIM Jong-In
        • HA JeongYong
        • BODDY Kate
        • ERNST Edzard
        Yoga for menopausal symptoms: a systematic review.
        Menopause. 2009; 16 (May): 602-608
        • CRAMER Holger
        • LAUCHE Romy
        • LANGHORST Jost
        • DOBOS Gustav
        Effectiveness of yoga for menopausal symptoms: a systematic review and meta-analysis of randomized controlled trials.
        Evidence-Based Complementary and Alternative Medicine. 2012; 2012 (November)863905
        • STERNFELD Barbara
        • GUTHRIE KatherineA.
        • ENSRUD KristineE.
        • LACROIX AndreaZ.
        • LARSON JosephC.
        • DUNN AndreaL.
        • ANDERSON GarnetL.
        • SEGUIN RebeccaA.
        • CARPENTER JanetS.
        • NEWTON KatherineM.
        • REED SusanD.
        • FREEMAN EllenW.
        • COHEN LeeS.
        • JOFFE Hadine
        • ROBERTS Melanie
        • CAAN BetteJ.
        Efficacy of exercise for menopausal symptoms: a randomized controlled trial.
        Menopause. 2014; 21 (April): 330-338
        • SAENSAK Suprawita
        • VUTYAVANICH Teraporn
        • SOMBOONPORN Woraluk
        • SRISURAPANONT Manit
        Relaxation for perimenopausal and postmenopausal symptoms.
        Cochrane Database of Systematic Reviews. July 2014; CD008582
        • CARPENTER JanetS.
        • BURNS DebraS.
        • WU Jingwei
        • OTTE JulieL.
        • SCHNEIDER Bryan
        • RYKER Kristin
        • TALLMAN Eileen
        • YU Menggang
        Paced respiration for vasomotor and other menopausal symptoms: a randomized, controlled trial.
        Journal of General Internal Medicine. 2013; 28 (February): 193-200
        • CARMODY JamesFrancis
        • CRAWFORD Sybil
        • LEUNG Katherine
        • CHURCHILL Linda
        • OLENDZKI Nicholas
        Mindfulness training for coping with hot flashes: results of a randomized trial.
        Menopause. 2011; 18 (June): 611-620