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Vasomotor Symptoms of Menopause

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Vasomotor Symptoms of Menopause, Hot Flashes, Hot Flushes, Flushing, Menopausal Diaphoresis

  • Epidemiology
  1. Vasomotor symptoms occur in 85% of perimenopausal women
    1. Starts 1-2 years before Menopause
    2. Continues for up to 5 years
  • 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
  • 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]
  • Management
  • Medications
  1. Hormonal agents (most effective)
    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. Selective Serotonin Reuptake Inhibitors
    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
      2. Venlafaxine (Effexor) and Desvenlafaxine (Khedezla)
    3. SSRIs shown to be effective
      1. 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]
      2. 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)
      3. 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]
  3. 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
  • 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]