Hot Flashes, or Flushes

Summarized by Robert W. Griffith, MD
January 8, 2003 (Reviewed: January 21, 2005)

Introduction

Although almost all women will get hot flashes (or hot flushes, as they are called in the UK) at some time in their lives, little is really known about their pathophysiology. Recent findings on the risks of hormone replacement therapy have renewed interest in the way in which they are caused, so that new treatment approaches may be developed. The Lancet has now published a review on these aspects.

Epidemiology

Hot flashes are a subjective feeling of heat, with cutaneous vasodilatation and a fall in core body temperature; there may also be sweating, flushing, palpitations, anxiety, irritation, and even panic. In 10% of cases women report them as 'nearly intolerable'. Their duration and frequency is quite variable: a few seconds to ten minutes, and every hour to several times a week.

Almost 80% of women have hot flashes during the perimenopause, lasting about a year; and a third of postmenopausal women have symptoms lasting 5 years, in some cases even longer. Hot flashes are more likely in women with low circulating estrogen levels, low bodyweight, low physical activity, smokers, African-Americans, and an early or abrupt (induced) menopause.

Hot flashes are associated with depression, nervousness, and insomnia; there may also be loss of libido. Reports of an association between breast cancer and hot flashes are difficult to interpret, because most such cancers occur in women over 50, and HRT is usually stopped when the cancer is diagnosed. Moreover, many breast cancer treatments include measures that may induce menopause - e.g. chemotherapy or endocrine therapy. Serotonin receptor modulators and aromatase inhibitors are also associated with an increased likelihood of hot flashes.

Physiology

It seems most probable that symptoms occur because of decreased estrogen or increased gonadotrophin concentrations, which affect brain neurotransmitters controlling the thermoregulatory set-point located in the anterior hypothalamus. Exactly how the changes in hormone levels affect neurotransmitters, and whether this is a direct effect or an indirect one - e.g. through norepinephrine hyperactivity - is unknown, to date. Serotonin may play an important role; a change in the balance between two serotonin receptors - 5HT2a and 5HT1a - has been shown in animal models to induce a vasomotor response to hot or cold stimuli, in order to restore the temperature status quo.

Treatment

A large number of non-medical treatments have been used, with variable degrees of success. Symptomatically, air conditioners, fans, and cold water are often used to alleviate the symptoms. Lifestyle changes - exercise, diet, smoking cessation - are advocated by some clinicians. Behavioral interventions, including meditation, applied relaxation, biofeedback, and paced respiration are advocated by others. The evidence in favor of the effectiveness of any of these is not strong.

One of the problems in evaluating treatments for hot flashes is the relatively high placebo response. Randomized placebo-control trials show a 20%-30% reduction in frequency and severity with placebo.

Very few adequate, well-controlled studies have been done with pharmaceutical interventions for hot flashes. Those considered relevant by these reviewers are summarized in the following table:

Agent	Population	Hot Flash Reduction by: Agent	Hot Flash Reduction by: placebo
Estrogen	Postmenopause	50% - 100%	..
Progestin	Breast cancer	71% - 90%	21% - 26%
Soy	Postmenopause, breast cancer	35% - 45%	25% - 38%
Black cohosh	Breast cancer	27% - 28%	30% - 32%
Vitamin E	Breast cancer	25%	22%
Clonidine	Breast cancer on tamoxifen	37% - 41%	20% - 27%
SSRIs	Postmenopause, breast cancer	34% - 65%	27% - 38%

The majority of studies have been done with estrogen, with results suggesting hot flashes are reduced by two to five times more often than with placebo. Transdermal patches may be an effective means of estrogen administration. Unfortunately, recent studies have shown that HRT carries a risk of increased breast cancer, and its use is now somewhat curtailed (see first link below). Results of comparable studies with estrogen-alone as replacement therapy (EHT) are outstanding.

Progestin has been shown to be effective in reducing hot flashes when give as a transdermal cream, tablets, or a vaginal gel. Adverse effects of progestin compounds include vaginal bleeding in about 30% of women, weight gain, and thromboembolism. Androgens given alone, or in combination with an estrogen, have been reported to be effective, but carry the risk of weight gain, bloating, hirsutism and acne.

Neuroendocrine agents

Clonidine, an alpha-2 adrenergic receptor antagonist, is about twice as effective as placebo in treating hot flashes. Side effects include dry mouth, constipation, and postural hypotension.

Selective serotonin-reuptake inhibitors (SSRIs), such as fluoxetine and sertraline, are also about twice as effective as placebo in reducing hot flashes. However, they can produce CNS and gastrointestinal side effects: malaise, sedation, agitation, headache, nausea, and anorexia. Sexual dysfunction is seen in as many as 15% of patients.

Complementary medicine options

As shown in the table above, vitamin E, soy, and black cohosh have not demonstrated superiority to placebo in well-controlled studies. Ginseng, red clover, and Chinese herbal remedies have also proved disappointing.

Comment

Hot flashes are very common, but their severity is variable. Women with disabling symptoms may well choose to take effective hormone treatment, in spite of a low risk of serious adverse effects. Depending on the circumstances, other pharmaceutical agents can be prescribed that should provide symptomatic relief in the majority of cases.

Source

• Hot flushes. V. Stearns, L. Ullmer, JF. Lopez,  et al., Lancet, 2002, pp. 1851--1861

Related Links
Perspectives on the Women's Health Initiative trial of hormone replacement therapy
A Non-Hormonal Treatment For Hot Flashes

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