Hot Flashes

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.