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Hot Flashes

Editor: Maggie Tetrokalashvili Updated: 12/19/2022 6:50:37 PM

Introduction

Hot flashes are sudden-onset, spontaneous, and episodic sensations of warmth usually felt on the chest, neck, and face immediately followed by sweating. They are the most common reason women seek medical care during the perimenopausal period, especially if the symptoms impair quality of life.[1] The onset of hot flashes can be associated with perspiration, heart palpitations, headache, weakness, fatigue, faintness, and anxiety, and warm environments, hot drinks, or emotional stress can trigger them. Hot flashes are variable in terms of duration, severity, and frequency. Frequency and severity can increase during the transition to menopause and peak approximately 1 year after the final menstrual period.[2] They can persist for 6 months to several years, usually decreasing in frequency and intensity over time after the final menstrual period.[2] On average, they last less than 5 minutes. The average frequency varies from 10 times daily to several times weekly.[2] The mean duration is 1.2 years.[2]

Etiology

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Etiology

The exact pathogenesis of hot flashes is unknown, but studies indicate that VMS (vasomotor symptoms) results from a central thermoregulatory function defect.[1] The physiological changes accompanying VMS are clear and well documented, yet several hypotheses about the mechanism of action exist. Various hormones and neurotransmitters modulate vasomotor symptoms, most importantly, estrogen. The thinking is that ovarian estrogen withdrawal is the initial mechanism leading to hot flashes. Norepinephrine and serotonin also have a role in the defect in thermoregulation with VMS, which is why SSRIs and SNRIs have been used to treat VMS.[1] Research documents that plasma levels of norepinephrine metabolites rise before and during a hot flash.[1] Peripheral vasodilation occurs, increasing to 10 to 15 degrees C in the fingers and toes.[3] A rise in systolic blood pressure and heart rate also occurs.[4]

Epidemiology

Hot flashes are among the most common types of menopausal vasomotor symptoms (VMS), affecting up to 74% of perimenopausal women.[1] Sixty-five percent of women complain of hot flashes for more than 2 years, and 36% for more than 5 years.[2]

History and Physical

Screening for hot flashes should take place in all perimenopausal women. Hot flashes should also receive treatment if they impair a woman's quality of life, particularly daytime activities and sleep. At the same time, many women have hot flashes and do not need treatment. In the most severe cases, a woman can awake several times during the night, which, in the long term, can cause cognitive and anxiety disorders.

Treatment / Management

Several treatment options exist, with only a few being FDA-approved. When selecting a treatment option, the healthcare provider should encourage the safest option first, such as lifestyle changes, and then proceed to the following hormonal or non-hormonal treatments. The most effective treatment for hot flashes is systemic estrogen, with a 75% reduction in VMS frequency.[5] Progestin therapy at high doses, including DMPA and megestrol, also decreases hot flashes but is not nearly as effective as estrogen.[6]  Progesterone treatment should be a consideration in women who cannot take estrogen therapy. Hormone therapy (HT) administration can be in various forms, including oral, parenteral, topical, transbuccal, vaginal, or transdermal, with each route having various formulations and doses of estrogen or progesterone.[7] The consensus is that HT for the treatment of hot flashes or vasomotor symptoms should be prescribed at the lowest effective dose for the shortest amount of time needed to manage the symptoms.[6] The safety of HT is controversial.(A1)

The Women's Health Initiative (WHI) is the largest study of its kind that evaluated hormone therapy risks in menopausal women. It was a multicenter, double-blind, placebo-controlled trial of women aged 50 to 79 at baseline, designed to assess HT’s impact on cardiovascular disease. Initial findings of the WHI reported that combined HT was not cardioprotective.[8] The WHI also found that HT increased the incidence of breast cancer, thromboembolic events, and stroke.[9] It is contraindicated in women with a history of breast cancer.[10]  As a result of the WHI findings, the current recommendation for the use of HT is to treat moderate to severe vasomotor symptoms at the lowest possible dose. An alternative to the conventional HT is compounded bioidentical hormones. Still, there is no evidence that these compounded products are as safe, effective, or superior to conventional HT for treating vasomotor symptoms.[11] Bioidentical hormone products currently FDA-approved include 17B-estradiol (transdermal or oral) and micronized progesterone (oral or vaginal). Non-FDA-approved bioidentical HT includes compounded preparations.[7][12](A1)

Since 2002, after the initial findings of the WHI were published, the use of HT decreased substantially (as much as 80%) as patients and providers turned to alternate forms of managing VMS.[13][14]  Non-prescribed, nonhormonal therapies studied include soy extract, red clover isoflavones, black cohosh, and Chinese herbs. Their safety and efficacy remain unclear. Although better quality studies are needed, some studies have found these nonhormonal options less effective than placebos.[9][12] (A1)

Prescription nonhormonal therapies include:

  • Gabapentin/pregabalin
  • Clonidine
  • SSRIs (paroxetine)
  • SNRIs (venlafaxine, desvenlafaxine)

These medications are more effective than placebos but not as effective as hormonal therapy.[9]  Paroxetine was the first nonhormonal prescription medication that was FDA-approved for use in treating menopausal vasomotor symptoms, including hot flashes.[15] The typically prescribed dose is an ultra-low 7.5 mg daily. It moderately reduces hot flashes versus the placebo.[15] Paroxetine and other SSRIs are not recommended for women with tamoxifen-induced hot flashes due to their effects as a strong inhibitor of the drug-metabolizing enzyme CYP2D6, therefore interfering with tamoxifen's therapeutic benefit.[16] SNRIs such as venlafaxine, although not FDA-approved for the treatment of hot flashes, are recommended for the management of hot flashes in a woman taking tamoxifen.[16] Other options for women with a history of breast cancer include gabapentin and clonidine.[16](A1)

Lifestyle changes such as exercise, layering clothes, maintaining lower room temperature, drinking cool drinks, and avoiding caffeine and alcohol are reasonable to consider for managing VMS, even if there aren't conclusive studies proving their efficacy.[17] Unfortunately, only limited studies exist for nonmedicated and integrative medical treatments of hot flashes, but research is growing in the integrative medicine field. Integrative medical treatments, including breathing exercises, relaxation techniques, changes in diet, yoga, acupuncture, reflexology, and hypnosis, could relieve vasomotor symptoms.[18]

Differential Diagnosis

Hot flashes are most commonly associated with perimenopause and menopause. In any woman presenting with hot flashes, whether she is perimenopausal age or status-post surgical or medically induced menopause, pathology must be ruled out as the cause. Menopause can be confirmed by the cessation of menses for at least 12 months and estradiol and FSH levels.

The differential diagnosis for hot flashes includes:

  • Carcinoid tumors
  • Systemic mastocytosis
  • Medullary carcinoma of the thyroid
  • Pheochromocytoma
  • Hyperthyroidism
  • Acromegaly
  • Idiopathic anaphylaxis [19]

Medications that can also cause hot flashes include:

  • Depo leuprolide
  • Clomiphene
  • Tamoxifen
  • Raloxifene
  • Tricyclic antidepressants
  • Monoamine oxidase inhibitors
  • Calcium channel blockers
  • Serotonin uptake inhibitors
  • Chemotherapy [19]

Hot flashes are a common (up to 80%) side effect in women taking tamoxifen.[1]

Prognosis

The prognosis of hot flashes is good. Most women's hot flashes resolve after 5 years. Only 10% of women have symptoms in the past 10 years.[2]

Complications

Nighttime hot flashes can awaken the patient and, over time, cause long-term sleep disruption. Research suggests that women with hot flashes may demonstrate an increased risk of cardiac disease and osteoporosis than women who do not have them.

Deterrence and Patient Education

A patient's first source of information should be their primary care provider or obstetrician and gynecologist. Patients can access patient education material online at the American College of Obstetricians, the American Society of Reproductive Specialists, and the North American Menopause Society.

Pearls and Other Issues

Key facts to keep in mind about hot flashes are as follows:

  1. Hot flashes are the most prevalent vasomotor symptom that presents during perimenopause. 
  2. The only FDA-approved nonhormonal prescription medication to treat hot flashes is low-dose paroxetine of 7.5 mg daily. 
  3. Nonhormonal nonprescription therapies, including black cohosh, red clover isoflavones, soy extract, and Chinese herbs, are not effective. 
  4. The Women's Health Initiative (WHI) found that combined HT raises the risk of breast cancer, venous thromboembolism, and stroke, is not cardioprotective, and does not decrease mortality risk. 
  5. The evidence is lacking to support the safety, effectiveness, and superiority of compounded bioidentical hormones over conventional hormone therapy.
  6. Although some SSRIs and SNRIs are safe and effective in treating hot flashes in patients with breast cancer, caution is necessary when used with tamoxifen. Gabapentin and clonidine can be alternatives for these patients.

Enhancing Healthcare Team Outcomes

Shared decision-making and communication between the gynecologist, nurse practitioner, primary care provider, nursing staff, pharmacy, and patient are critical in managing hot flashes. The patient should be well educated on her diagnosis, what to expect during the perimenopausal period, and her treatment options, including the risks, benefits, and alternatives of each therapy. They should receive counsel that HT has been proven safe and effective in treating VMS. They should receive education about the FDA approval status of the different forms of therapies. All these approaches are best handled by an interprofessional team incorporating the abovementioned personnel to deliver optimal patient care during menopause. Ambulatory care nurses are often the first contact for patients. After diagnosis, clinicians should monitor patients and provide follow-up to the interprofessional team. Pharmacists educate patients about side effects and compliance and check for drug interactions.

References


[1]

Rapkin AJ. Vasomotor symptoms in menopause: physiologic condition and central nervous system approaches to treatment. American journal of obstetrics and gynecology. 2007 Feb:196(2):97-106     [PubMed PMID: 17306645]


[2]

Politi MC, Schleinitz MD, Col NF. Revisiting the duration of vasomotor symptoms of menopause: a meta-analysis. Journal of general internal medicine. 2008 Sep:23(9):1507-13. doi: 10.1007/s11606-008-0655-4. Epub 2008 Jun 3     [PubMed PMID: 18521690]

Level 2 (mid-level) evidence

[3]

Freedman RR. Physiology of hot flashes. American journal of human biology : the official journal of the Human Biology Council. 2001 Jul-Aug:13(4):453-64     [PubMed PMID: 11400216]


[4]

Gerber LM,Sievert LL,Warren K,Pickering TG,Schwartz JE, Hot flashes are associated with increased ambulatory systolic blood pressure. Menopause (New York, N.Y.). 2007 Mar-Apr;     [PubMed PMID: 17213753]

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Maclennan AH, Broadbent JL, Lester S, Moore V. Oral oestrogen and combined oestrogen/progestogen therapy versus placebo for hot flushes. The Cochrane database of systematic reviews. 2004 Oct 18:2004(4):CD002978     [PubMed PMID: 15495039]

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Nelson HD. Menopause. Lancet (London, England). 2008 Mar 1:371(9614):760-70. doi: 10.1016/S0140-6736(08)60346-3. Epub     [PubMed PMID: 18313505]


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North American Menopause Society. The 2012 hormone therapy position statement of: The North American Menopause Society. Menopause (New York, N.Y.). 2012 Mar:19(3):257-71. doi: 10.1097/gme.0b013e31824b970a. Epub     [PubMed PMID: 22367731]


[8]

Hodis HN, Mack WJ, Henderson VW, Shoupe D, Budoff MJ, Hwang-Levine J, Li Y, Feng M, Dustin L, Kono N, Stanczyk FZ, Selzer RH, Azen SP, ELITE Research Group. Vascular Effects of Early versus Late Postmenopausal Treatment with Estradiol. The New England journal of medicine. 2016 Mar 31:374(13):1221-31. doi: 10.1056/NEJMoa1505241. Epub     [PubMed PMID: 27028912]


[9]

Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, Jackson RD, Beresford SA, Howard BV, Johnson KC, Kotchen JM, Ockene J, Writing Group for the Women's Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. JAMA. 2002 Jul 17:288(3):321-33     [PubMed PMID: 12117397]

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Holmberg L, Anderson H, HABITS steering and data monitoring committees. HABITS (hormonal replacement therapy after breast cancer--is it safe?), a randomised comparison: trial stopped. Lancet (London, England). 2004 Feb 7:363(9407):453-5     [PubMed PMID: 14962527]

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Boothby LA, Doering PL, Kipersztok S. Bioidentical hormone therapy: a review. Menopause (New York, N.Y.). 2004 May-Jun:11(3):356-67     [PubMed PMID: 15167316]


[12]

Shifren JL, Gass ML, NAMS Recommendations for Clinical Care of Midlife Women Working Group. The North American Menopause Society recommendations for clinical care of midlife women. Menopause (New York, N.Y.). 2014 Oct:21(10):1038-62. doi: 10.1097/GME.0000000000000319. Epub     [PubMed PMID: 25225714]


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Jewett PI, Gangnon RE, Trentham-Dietz A, Sprague BL. Trends of postmenopausal estrogen plus progestin prevalence in the United States between 1970 and 2010. Obstetrics and gynecology. 2014 Oct:124(4):727-733. doi: 10.1097/AOG.0000000000000469. Epub     [PubMed PMID: 25198271]

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[14]

Manson JE,Kaunitz AM, Menopause Management--Getting Clinical Care Back on Track. The New England journal of medicine. 2016 Mar 3     [PubMed PMID: 26962899]


[15]

Simon JA, Portman DJ, Kaunitz AM, Mekonnen H, Kazempour K, Bhaskar S, Lippman J. Low-dose paroxetine 7.5 mg for menopausal vasomotor symptoms: two randomized controlled trials. Menopause (New York, N.Y.). 2013 Oct:20(10):1027-35. doi: 10.1097/GME.0b013e3182a66aa7. Epub     [PubMed PMID: 24045678]

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[16]

Desmarais JE, Looper KJ. Managing menopausal symptoms and depression in tamoxifen users: implications of drug and medicinal interactions. Maturitas. 2010 Dec:67(4):296-308. doi: 10.1016/j.maturitas.2010.08.005. Epub 2010 Sep 28     [PubMed PMID: 20880642]


[17]

Thurston RC, Joffe H. Vasomotor symptoms and menopause: findings from the Study of Women's Health across the Nation. Obstetrics and gynecology clinics of North America. 2011 Sep:38(3):489-501. doi: 10.1016/j.ogc.2011.05.006. Epub     [PubMed PMID: 21961716]


[18]

. ACOG Practice Bulletin No. 141: management of menopausal symptoms. Obstetrics and gynecology. 2014 Jan:123(1):202-216. doi: 10.1097/01.AOG.0000441353.20693.78. Epub     [PubMed PMID: 24463691]


[19]

Izikson L, English JC 3rd, Zirwas MJ. The flushing patient: differential diagnosis, workup, and treatment. Journal of the American Academy of Dermatology. 2006 Aug:55(2):193-208     [PubMed PMID: 16844500]