II. Epidemiology

  1. Vasomotor symptoms occur in 85% of perimenopausal women
    1. Starts 1-2 years before Menopause
    2. Continues for up to 5 years

III. Differential Diagnosis

  1. Medications
    1. Isoniazid
    2. Disulfiram reaction
      1. Griseofulvin
      2. Flagyl
      3. Chlorpropamide
      4. Chloral Hydrate
    3. Niacin
    4. Hydralazine
    5. Calcitonin
    6. Aspirin sensitive
    7. Procardia
    8. Capsaicin
    9. MAO inhibitor when taken with Tyramine (beer, cheese)
  2. Medication Withdrawal
    1. Clonidine Withdrawal
    2. Alpha-Methyldopa withdrawal
    3. Alcohol Withdrawal
  3. Pheochromocytoma
  4. Carcinoid
  5. Mastocytosis in Leukemia
    1. Histamine and Prostaglandin D Release
    2. Hypotensive episodes
    3. Dermatographia
  6. VIP-oma or WDHA: Diarrhea, Hypokalemia, achlorhydria
  7. Menopausal Flushing
  8. Emotional blushing
  9. Food and Environmental Stimuli
    1. Monosodium glutamate
    2. Thermal stimuli
    3. Ethanol (worse with Rosacea, Carcinoid, Mastocytosis)
    4. Scombroid Fish Poisoning: Tuna, Mahi-mahi, Mackerel
  10. Syndrome obscure in women
    1. Characteristics
      1. Telangiectasia
      2. Urticaria
      3. Flushing
      4. Peptic Ulcer Disease
      5. Diarrhea
    2. Increased blood and urine histamine
    3. Not associated with Mastocytosis or Carcinoid

IV. Management: Lifestyle

  1. Precautions
    1. No single lifestyle modification has been found consistently effective in Hot Flashes
    2. However, many lifestyle measures listed have broader health benefits (e.g. weight loss, Tobacco Cessation)
    3. (2015) Menopause 22(11): 1155-72 [PubMed]
    4. Kaunitz (2015) Obstet Gynecol 126(4): 859-76 [PubMed]
  2. General measures (no strong evidence of benefit)
    1. Wear cool clothing (e.g. breathable)
    2. Use a fan
    3. Drink cool liquids and eat cold foods
  3. Regular Exercise has mixed results (no strong evidence of benefit)
    1. Original study supported Exercise as effective
      1. Ivarsson (1998) Maturitas 29:139-46 [PubMed]
    2. Recent study does not show benefit in Hot Flushes
      1. Aiello (2004) Menopause 11:382-8 [PubMed]
  4. Avoid Exacerbating food products (no strong evidence of benefit)
    1. Caffeine
    2. Alcohol in excess
    3. Spicy food
    4. Dietary Fat intake
      1. Associated with Hot Flushes in Postmenopause
      2. Riley (2004) J Gen Intern Med 19:740-6 [PubMed]
  5. Vitamin Supplementation (no strong evidence of benefit)
    1. Vitamin B6 may be helpful
    2. Vitamin E is no more effective than Placebo
  6. Other measures associated with decreased symptoms (no strong evidence of benefit)
    1. Tobacco Cessation
    2. Yoga
    3. Massage
    4. Meditation
    5. Leisurely bath
    6. Weight loss
      1. Associated with less Hot Flushes in Perimenopause
      2. Riley (2004) J Gen Intern Med 19:740-6 [PubMed]

V. Management: Medications

  1. Hormonal agents (most effective, but review risks and contraindications)
    1. Estrogen Replacement Therapy
      1. Relieves symptoms in 80-90% of patients
    2. Progestin
      1. Progesterone transdermal cream (20 grams/day)
        1. Leonetti (1999) Obstet Gynecol 94:225-8 [PubMed]
      2. Megestrol acetate (Megace) 20 mg PO bid
        1. Relieves symptoms ~50% of cases
      3. Medroxyprogesterone acetate (Provera) 20 mg orally daily
        1. Relieves symptoms ~50% of cases
  2. Serotonin Norepinephrine Reuptake Inhibitor (SNRI)
    1. Efficacy
      1. Venlafaxine appears to be most effective among SNRI and SSRI agents
      2. However, SNRIs also have more side effects than SSRIs (e.g. Nausea, Dry Mouth, Constipation)
    2. Desvenlafaxine (Khedezla)
    3. Venlafaxine (Effexor)
      1. Dose: 12.5 mg orally twice daily or 75 mg orally at bedtime
      2. (1998) J Clin Oncol 16:2377 [PubMed]
      3. Loprinzi (2000) Lancet 356:2059-63 [PubMed]
  3. Selective Serotonin Reuptake Inhibitors (SSRI)
    1. Efficacy
      1. More effective and better tolerated than Clonidine or Gabapentin
    2. Precaution: Avoid Prozac and Paxil in Breast Cancer patients on Tamoxifen
      1. CYP2D6 Inhibitors (e.g. Paroxetine, Fluoxetine, Bupropion) may decrease Tamoxifen efficacy
    3. SSRIs shown to be effective
      1. Paroxetine (Paxil CR)
        1. Paroxetine 12.5 to 25 mg orally daily
          1. Stearns (2003) JAMA 289:2827-34 [PubMed]
        2. Released as Brisdelle (7.5 mg Paroxetine) in 2013 specifically targeting Hot Flushes
          1. Paroxetine 10 mg generic tablet daily is nearly equivalent (at 6% of the Brisdelle cost)
      2. Fluoxetine (Prozac)
        1. Loprinzi (2002) J Clin Oncol 20:1578-83 [PubMed]
    4. SSRIs not found to be effective
      1. Citalopram (Celexa)
      2. Sertraline (Zoloft)
      3. Suvanto-Luukkonen (2005) Menopause 12:18-26 [PubMed]
  4. Miscellaneous agents with some efficacy against Hot Flushes
    1. Clonidine 0.1 - 0.2 mg PO qhs (or transdermal patch)
      1. Modest benefit, but adverse effects (Hypotension, Dizziness) may limit use
      2. (1994) JCO 12:155
    2. Gabapentin (Neurontin) 300 mg orally three times daily
      1. Guttuso (2003) Obstet Gynecol 101:337-45 [PubMed]
    3. Bellergal-S 100
      1. Small risk of addiction
    4. Aldomet 250 mg PO bid

VI. Management: Herbals and Dietary Supplements

  1. Possible benefit
    1. Omega-3 Fatty Acids
    2. Black Cohosh
      1. Hernandez (2003) Maturitas 44:S59-65 [PubMed]
    3. Soy Isoflavones or Phytoestrogens
      1. See Soy Protein
      2. Original studies with mixed results (prior to consideration of pharmacogenomic factors )
        1. Faure (2002) Menopause 9:329-34 [PubMed]
        2. Han (2002) Obstet Gynecol 99:389-94 [PubMed]
        3. Nikander (2003) Obstet Gynecol 101:1213-20 [PubMed]
      3. Effectiveness appears dependent on pharmacogenomic factors
        1. Equol is a soy metabolite with Estrogenic Activity
        2. Only 40% of North American women convert Soy Isoflavone (daidzein) to equol
          1. Conversion is most common in Asian and Hispanic women
          2. The majority who lack this conversion are unlikely to see benefit from soy
        3. References
          1. Clarkson (2011) Menopause 18(7):732-53 [PubMed]
  2. Unlikely benefit
    1. Dong Quai (No better than Placebo)
    2. Evening Primrose Oil
    3. Red Clover
      1. Tice (2003) JAMA 290:207-14 [PubMed]
    4. Vitamin E slightly better than Placebo
      1. Barton (1998) J Clin Oncol 16:495-500 [PubMed]

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Related Studies

Ontology: Flushing (C0016382)

Definition (HL7V3.0) <p>Flush</p>
Definition (NCI_CTCAE) A disorder characterized by episodic reddening of the face.
Definition (NCI) Reddening of the skin from a transient increase in blood flow.
Definition (MSH) A transient reddening of the face that may be due to fever, certain drugs, exertion, stress, or a disease process.
Concepts Sign or Symptom (T184)
MSH D005483
ICD9 782.62
ICD10 R23.2
SnomedCT 206902002, 158255000, 238810007, 20255002, 271811009
HL7 2.16.840.1.113883.1.11.14594
LNC LA17201-7
English Flushings, FLUSHING, SKIN FLUSHED, [D]Flushing, [D]Flushing (context-dependent category), cutaneous vascular engorgement, flushing reaction, skin reddening, sudden redness of skin (symptom), skin flushing as symptom, sudden redness of skin, sudden redness of skin primarily involving face, flushing, facial flushing, sudden redness of skin primarily involving face (symptom), Flushed face, Flushing of face, Facial flushing, Flushed, Flushed skin, Skin flushed, Flushing [Disease/Finding], face flushed, flushing face, flushed, face flushing, flushing of face, flushing facial, flush face, skin flush, facial flush, flushed skin, face flush, flush, flushes, reddened skin, flushed face, [D]Flushing (situation), Flush, Face goes red, Flushes, Face goes red (finding), Flushing (disorder), Flushing
Dutch plotseling rood gezicht, plotseling rood wordend gezicht, plotseling rode huid, plotselinge 'roodheid gezicht, huid plotseling rood, blozend, Opvliegingen [flushes], overmatig blozen, Blozen
French Rougeurs du visage, Rougeur de la peau, Aspect congestionné, Bouffées vasomotrices au visage, BRUSQUE ROUGEUR DE LA PEAU, ROUGEUR CONGESTIVE, Bouffée congestive, Rougeur de la face, Rougeur du visage, Bouffées congestives, Bouffées vasomotrices
German geroetetes Gesicht, Gesichtsroetung, geroetete Haut, Gesichtserroetung, Haut geroetet, geroetet, FLUSH, Gesichtsroetung [Flush], HAUTGEFAESSERWEITERUNG, Hitzegefuehl, Flushing
Italian Faccia arrossata, Cute arrossata, Arrossato, Vampate alla faccia, Rossore facciale, Rossore
Portuguese Ruborizado, Pele ruborizada, Face ruborizada, AFRONTAMENTO, RUBOR SUBITO DA PELE, Enrubescimento, Vermelhidão Facial, Rubidez Facial, Enrubescimento da Pele do Rosto, Ruborização Facial, Rubificação Facial, Afrontamento, Rubor
Spanish Congestión facial, Piel enrojecida, Enrojecido, Cara enrojecida, Rubefacción de la cara, [D]rubefacción (categoría dependiente del contexto), PIEL, ENROJECIMIENTO, RUBEFACION, [D]rubefacción, [D]rubefacción (situación), Rubefacción Facial, Rubor Facial, Enrojecimiento de la Piel, Enrojecimiento de la Cara, Rubicundez Facial, Acaloramiento, Enrojecimiento, enrojecimiento facial (hallazgo), enrojecimiento facial, rubor (trastorno), rubor, Rubefacción, Rubor
Japanese 顔面潮紅, 潮紅, 皮膚潮紅, ガンメンチョウコウ, チョウコウ, ヒフチョウコウ
Swedish Rodnad
Czech zrudnutí, Zrudlá kůže, Zrudnutí, Zrudnutí obličeje, Zrudlá tvář, Zrudlý
Finnish Flushing
Korean 홍조
Croatian ZARUMEN
Polish Wypieki na twarzy, Nagłe zaczerwienienie twarzy, Uderzenie krwi do głowy
Hungarian Kipirulás, Bőr kipirult, Kipirult arc, Kipirult, Kipirult bőr, Arc kipirulása, Arcpír
Norwegian Sprutrødming, Sprutrødme

Ontology: Hot flushes (C0600142)

Definition (NCI_NCI-GLOSS) A sudden, temporary onset of body warmth, flushing, and sweating (often associated with menopause).
Definition (NCI) A temporary feeling of intense body warmth, flushing, sometimes accompanied by sweating. A common, symptom of menopause; other conditions that can produce hot flushes include antidepressants and drugs blocking the effect of estrogens, carcinoid tumors and a sensitivity to sulfites or other food additives.
Definition (NCI_CTCAE) A disorder characterized by an uncomfortable and temporary sensation of intense body warmth, flushing, sometimes accompanied by sweating upon cooling.
Definition (MSH) A sudden, temporary sensation of heat predominantly experienced by some women during MENOPAUSE. (Random House Unabridged Dictionary, 2d ed)
Definition (CSP) sudden, temporary sensation of heat predominantly experienced by women during menopause, and as a side effect of some hormone therapies.
Concepts Sign or Symptom (T184)
MSH D019584
SnomedCT 427368007, 389318003, 67443009, 390053008, 198436008
English HOT FLUSHES, Flashes, Hot, Hot Flashes, Hot flushes, Climacteric flushing, Climacteric flushing (disorder), hot flashes, hot flashes (symptom), Feeling of hot flushes, Flash hot, Flush hot, Hot flushes NOS, Hot flushes menopausal, Hot flushes, menopausal, Menopause flushing, Hot Flashes [Disease/Finding], hot flushes, flushed hot, Hot flushes;menopausal, hot flush menopausal symptom, flushing hot, flushes hot, Hot flushes (finding), Hot flash, Hot flash (finding), hot flash, HOT FLASHES, FLASHES, HOT, Menopausal flushing, Menopausal hot flushes, Menopausal flushing (finding), hot flush, flushing; menopausal, menopausal; flushing, Hot flush, Hot flashes, Hot Flash, menopausal hot flushes
Italian Vampata di calore, Vampate di calore, Vampate di calore da menopausa, Vampate di calore NAS, Vampate di calore menopausali, Vampate menopausali, Sensazione di vampate di calore, Vampate
Dutch gevoel van opvliegers, opvliegers NAO, opvliegers, menopauzaal, menopauzale opvliegers, opvliegers, flushes; menopauzaal, menopauze; flushes, opvlieger, Opvlieging, Opvliegingen
French Bouffées de chaleur de la ménopause, Bouffées de chaleur ménopausiques, Sensation de bouffées de chaleur, Bouffées de chaleur au visage et au cou, Bouffées de chaleur SAI, Bouffées de chaleur, ménopausiques, Bouffées de chaleur liées à la ménopause, BOUFFEES DE CHALEUR, Bouffée de chaleur, Bouffées de chaleur
German Hitzewallung menopausal, menopausale Hitzwallungen, Hitzeanfaelle, menopausale Hitzewallung, Hitzewallung, menopausal, Gefuehl von Hitzewallungen, Hitzeanfall, Hitzewallungen NNB, HITZEWALLUNGEN, Hitzewallung, Hitzewallungen
Portuguese Afrontamentos, Afrontamentos menopáusicos, Calor, Sensação de afrontamentos, Afrontamentos com sensação de calor NE, Afrontamento da menopausa, EPISODIO AGUDO DE CALOR, Rubor quente, Fogachos
Spanish Sofocos menopáusicos, Sensación de sofoco, Sofocos NEOM, Sofocos, menopausia, sofocones climatéricos, sofocones climatéricos (trastorno), CALOR, SENSACION DE, calores, sofocones, calores (hallazgo), soflama, Sofoco, Bochorno, Bochornos, sofocones menopáusicos (hallazgo), sofocones menopáusicos, Acaloramiento, Sofocos
Japanese ほてりNOS, 閉経期顔面紅潮, ほてり感, ほてり, ホテリ, ホテリNOS, ホテリカン, ヘイケイキガンメンコウチョウ
Swedish Blodvallningar
Czech návaly, Pocit návalů horka, Návaly horka, Menopauzální návaly, Návaly horka v menopauze, Návaly horka, v menopauze, Menopauzální návaly horka, Nával horka, Návaly horka NOS
Finnish Kuumat aallot
Polish Uderzenie krwi do głowy w menopauzie
Hungarian höhullám, menopausalis hőhullámok, Kivörösödéshőhullám megélése, Hőhullám, Hőhullámok, Menopausalis hőhullámok, Kipirulások k.m.n., Menopausalis kipirulás, Pirulás
Norwegian Hetetokter

Ontology: Menopausal diaphoresis (C1262243)

Concepts Disease or Syndrome (T047)
Dutch menopauzale diaforese
French Diaphorèse ménopausique
German vermehrtes Schwitzen in der Menopause
Italian Diaforesi menopausale
Portuguese Diaforese menopáusica
Spanish Diaforesis menopáusica
Japanese 閉経期発汗, ヘイケイキハッカン
Czech Menopauzální diaforéza
Hungarian Menopausalis izzadás
English Menopausal diaphoresis