II. Epidemiology
- Vasomotor symptoms occur in 85% of perimenopausal women
- Starts 1-2 years before Menopause
- Continues for up to 5 to 8 years
III. Differential Diagnosis
- Medications
- Isoniazid
- Disulfiram reaction
- Niacin
- Hydralazine
- Calcitonin
- Aspirin sensitive
- Procardia
- Capsaicin
- MAO Inhibitor when taken with Tyramine (beer, cheese)
-
Medication Withdrawal
- Clonidine Withdrawal
- Alpha-Methyldopa withdrawal
- Alcohol Withdrawal
- Pheochromocytoma
- Carcinoid
-
Mastocytosis in Leukemia
- Histamine and Prostaglandin D Release
- Hypotensive episodes
- Dermatographia
- VIP-oma or WDHA: Diarrhea, Hypokalemia, achlorhydria
- Menopausal Flushing
- Emotional blushing
- Food and Environmental Stimuli
- Monosodium Glutamate
- Thermal stimuli
- Ethanol (worse with Rosacea, Carcinoid, Mastocytosis)
- Scombroid Fish Poisoning: Tuna, Mahi-mahi, Mackerel
- Syndrome obscure in women
- Characteristics
- Increased blood and urine Histamine
- Not associated with Mastocytosis or Carcinoid
IV. Management: Nonpharmacologic and Lifestyle
- Precautions
- No single lifestyle modification has been found consistently effective in Hot Flashes
- However, many lifestyle measures listed have broader health benefits (e.g. weight loss, Tobacco Cessation)
- (2015) Menopause 22(11): 1155-72 [PubMed]
- Kaunitz (2015) Obstet Gynecol 126(4): 859-76 [PubMed]
-
General measures (no strong evidence of benefit)
- Wear cool clothing (e.g. breathable)
- Use a fan
- Drink cool liquids and eat cold foods
- Avoid Exacerbating food products (no strong evidence of benefit)
- Caffeine
- Alcohol in excess
- Spicy food
- Dietary Fat intake
- Associated with Hot Flushes in Postmenopause
- Riley (2004) J Gen Intern Med 19:740-6 [PubMed]
-
Vitamin Supplementation (no strong evidence of benefit)
- Vitamin B6 may be helpful
- Vitamin E is no more effective than Placebo
- Weight loss
- Associated with less Hot Flushes in Perimenopause
- Riley (2004) J Gen Intern Med 19:740-6 [PubMed]
- Behaviorial Interventions
- Regular Exercise has mixed results (no strong evidence of benefit)
- Original study supported Exercise as effective
- Recent study does not show benefit in Hot Flushes
- Other measures without strong evidence of benefit in Vasomotor Symptom Reduction
- Tobacco Cessation
- Yoga
- Massage
- Meditation
- Leisurely bath
V. Management: Medications
- Hormonal agents (most effective, but review risks and contraindications)
- Estrogen Replacement Therapy
- Relieves symptoms in 80-90% of patients
- Progestin (less effective than Estrogen containing options)
- Progesterone transdermal cream (20 grams/day)
- Megestrol acetate (Megace) 20 mg PO bid
- Relieves symptoms ~50% of cases
- Medroxyprogesterone acetate (Provera) 20 mg orally daily
- Relieves symptoms ~50% of cases
- Tissue-selective Estrogen Complex (TSEC): Estrogen with Selective Estrogen Receptor Modulator (SERM)
- Duavee is a combination of Estrogen AND Bazedoxifene (BZA)
- First TSEC released in U.S. 2019
- Significantly reduces vasomotor symptoms without affecting Breast tissue, endometrium or VTE or Cardiac Risk
- Lello (2017) Int J Endocrinol 2017:5064725 +PMID: 29358948 [PubMed]
- Estrogen Replacement Therapy
-
Serotonin Norepinephrine Reuptake Inhibitor (SNRI)
- Efficacy
- Venlafaxine appears to be most effective among SNRI and SSRI agents
- Venlafaxine does not affect Tamoxifen metabolism (unlike some SSRIs that are CYP2D6 Inhibitors)
- However, SNRIs also have more side effects than SSRIs (e.g. Nausea, Dry Mouth, Constipation, Somnolence)
- Desvenlafaxine (Khedezla)
- Venlafaxine (Effexor)
- Dose: 12.5 mg orally twice daily or 75 mg orally at bedtime
- (1998) J Clin Oncol 16:2377 [PubMed]
- Loprinzi (2000) Lancet 356:2059-63 [PubMed]
- Efficacy
-
Selective Serotonin Reuptake Inhibitors (SSRI)
- Efficacy
- More effective and better tolerated than Clonidine or Gabapentin
- Precaution: Avoid Prozac and Paxil in Breast Cancer patients on Tamoxifen
- CYP2D6 Inhibitors (e.g. Paroxetine, Fluoxetine, Bupropion) may decrease Tamoxifen efficacy
- Other SSRIs inhibit CYP2D6 but less potently
- SSRIs shown to be effective
- Paroxetine (Paxil CR)
- Paroxetine 12.5 to 25 mg orally daily
- Released as Brisdelle (7.5 mg Paroxetine) in 2013 specifically targeting Hot Flushes
- Paroxetine 10 mg generic tablet daily is nearly equivalent (at 6% of the Brisdelle cost)
- Fluoxetine (Prozac)
- Paroxetine (Paxil CR)
- SSRIs not found to be effective
- Efficacy
- Miscellaneous agents with some efficacy against Hot Flushes
- Clonidine
- Start 0.1 mg orally at bedtime (or 0.1 mg weekly transdermal patch)
- May titrate to 0.2 mg orally at bedtime and up to 0.2 mg orally twice daily
- Modest benefit, but adverse effects (Hypotension, Dizziness) may limit use
- (1994) JCO 12:155
- Gabapentin (Neurontin)
- Dosing: Titrate to 300 mg orally three times daily
- Guttuso (2003) Obstet Gynecol 101:337-45 [PubMed]
- Neurokinin 3 Receptor Antagonist (e.g. Fezolinetant or Veozah)
- Fezolinetant (Veozah) 45 mg orally daily
- Requires hepatic profile monitoring (baseline, and at 3, 6, and 9 months)
- Cost $550 per month when released in 2023
- Less effective than hormonal therapy, but similar to SNRIs, SSRIs and Gabapentin in hot flash reduction
- Blocks neurokinin B (NKB) at the infundibular nucleus of the Hypothalamus
- Neurokinin B (NKB) regulates temperarture and its blockade can decrease Vasomotor Symptoms of Menopause (Hot Flashes)
- Clonidine
- Other agents with historic use
- Aldomet 250 mg PO bid
- Bellergal-S 100
- Small risk of addiction
VI. Management: Herbals and Dietary Supplements
- Possible benefit
- Omega-3 Fatty Acids
- Black Cohosh
- Soy Isoflavones or Phytoestrogens
- See Soy Protein
- Original studies with mixed results (prior to consideration of pharmacogenomic factors )
- Effectiveness appears dependent on pharmacogenomic factors
- Equol is a soy metabolite with Estrogenic Activity
- Only 40% of North American women convert Soy Isoflavone (daidzein) to equol
- Conversion is most common in Asian and Hispanic women
- The majority who lack this conversion are unlikely to see benefit from soy
- References
- Unlikely benefit
- Dong Quai (No better than Placebo)
- Evening Primrose Oil
- Red Clover
- Vitamin E slightly better than Placebo
VII. References
- Carroll (2006) Am Fam Physician 73:457-67 [PubMed]
- Chang (2023) Am Fam Physician 108(1): 28-39 [PubMed]
- Diem (2020) Menopause 27(10): 1126-36 [PubMed]
- Handley (2015) J Am Assoc Nurse Pract 27(1): 54-61 [PubMed]
- Hill (2016) Am Fam Physician 94(11): 884-9 [PubMed]
- Israel (1997) Pharmacotherapy 17:970-84 [PubMed]
- Morelli (2002) Am Fam Physician 66(1):129-34 [PubMed]
- Shanafelt (2002) Mayo Clin Proc 77:1159-63 [PubMed]
Images: Related links to external sites (from Bing)
Related Studies
| 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, ｶﾞﾝﾒﾝﾁｮｳｺｳ, 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 |
| Russian | PRILIV KROVI, POKRASNENIE, KROVI PRILIV, КРОВИ ПРИЛИВ, ПРИЛИВ КРОВИ, ПОКРАСНЕНИЕ |
| 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, ﾍｲｹｲｷｶﾞﾝﾒﾝｺｳﾁｮｳ |
| 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 |
| Russian | PRILIVY KLIMAKTERICHESKIE, KLIMAKTERICHESKIE PRILIVY, КЛИМАКТЕРИЧЕСКИЕ ПРИЛИВЫ, ПРИЛИВЫ КЛИМАКТЕРИЧЕСКИЕ |
| 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 |
