Treating Hot Flashes

By Thomas J. Smith, MD, FACP

My fridays are mostly for breast cancer patients: receiving adjuvant therapy after a half-day at work, coming in for follow-up, living with recurrent disease as best they can. A uniform complaint is hot flashes—not just a little warmth, but uncomfortable sweats that interfere with work and especially sleep. I have kept a file of mostly useless, semi-homeopathic, or unevaluated therapies over the years.

Finally, however, we have some decent treatments that do not seem to be well known. The head of a new university Women’s Health Program was not aware of some new treatments when I recently queried her. So, here is the evolution of one physician’s thinking and the new data.

Hot Flashes are Common

From the tamoxifen trials, we know that about 40% of women will be bothered with them. Raloxifene (which seems to be getting prescribed for adjuvant hormonal therapy without much evidence—but that’s another story) causes hot flashes in about 25% of women.

In my standardized breast cancer patient review of systems, including hot flashes, sexual function, etc., hot flashes are remarkable in their prevalence.

And, it’s not just women anymore. For men receiving neo-adjuvant hormonal therapy for prostate cancer, 80% had hot flashes, and 11% continued with them after the hormone treatments stopped.1

Hot Flashes may be Important for Compliance

Forget the discomfort for a minute, since we oncologists ask our patients to put up with an amazing variety of symptoms. Hot flashes may be one of the reasons why 6% of patients simply cannot tolerate tamoxifen. In the Italian trial of tamoxifen as a chemopreventative, temporary discontinuation was common (5.4%) and about one-fourth of those who stopped did so permanently.2

OK, What Works?

Venlafaxine hydrochloride (Effexor), 12.5 mg bid works. This is 10-20% of the dose used for depression. It reduced the number of hot flashes from 6.6 to 4.3 per day. Fifty-four percent of these 28 patients had a decrease in the numbers of 50% or more. The average number of severe/very severe hot flashes declined from 1.4/d to 0.1/d.3 Some healthcare plans may not cover it for depression—hoping to reduce costs by stocking only a few anti-depressants—but, sometimes, an explanation of its benefits will convince them to cover it for a particular patient. Patients are often willing to pay $30 for a trial prescription.

Megestrol acetate 20 mg bid works. In a placebo-controlled trial, 74% of patients had a decrease of 50% or more compared to 20% with placebo. The only side effect was estrogen withdrawal bleeding 1-2 weeks after stopping the megestrol acetate. (It is especially important to warn vigilant or hypervigilant women who are worried about endometrial cancer from tamoxifen. The rate of 1/100 women over 5 years developing endometrial cancer is not reassuring to them.)4 Recent updates from this trial confirm that 45% of patients continued to use megestrol acetate at three years, usually less than 20 mg daily. Some episodes of chills, weight gain, vaginal bleeding, and carpal tunnel syndrome were reported but the drug appears to be well tolerated in the long term.5

Vitamin E does not work, or at least does not work well enough to recommend it.6 The one placebo-controlled trial showed that vitamin E was not preferred over placebo, and that vitamin E and placebo had a similar reduction in hot flashes (25% vs 22%, NS.) In the subsequent cross-over period, one less hot flash per day was seen in those who crossed over to vitamin E. To my review, this negative randomized clinical trial negates all the anecdotal evidence that vitamin E helps (after all, that is why we do randomized, placebo controlled trials!) but since there was no toxicity, many of my patients still take vitamin E.

Clonidine works. Oral doses of 0.1-0.4 mg bid reduced the occurrence of hot flashes 46%.7 Only the 0.2 and 0.4 mg doses had enough effect to be worthwhile, and four of 10 patients discontinued the drugs due to nausea, fatigue, irritability, and dizziness. I had patients start with one-fourth of a 1.0 mg pill bid.

Clonidine transdermal patches work. The clonidine transdermal therapeutic system reduced the frequency of hot flashes from 80% to 36% compared with placebo, with similar improvements in severity.8 Side effects were minimal with no significant changes in blood pressure or pulse rate.

Placebo works! About 20-30% of patients will have partial abatement of hot flashes—which is why placebocontrolled trials are so important.

Table
Summary of the Data
Drug % Reduction in hot flash score
Venlafaxine 12.5 mg bid
55
Megestrol acetate 20 mg bid
85
Clonidine patches
33
Placebo
21-25
Modified from Loprinzi CL, et al. J Clin Oncol 1998;16:2377-2381.
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The Take Home Message

Hot flashes are common in men and women undergoing hormonal changes. Hot flashes bother people, both men and women. There is effective therapy available, with minimal side effects. We should routinely add, "Are you having hot flashes?" to our review of systems for each person on hormonal therapy and, if the hot flashes are bothering them, prescribe some effective treatment. (Dr. Smith is Director of Cancer Education, Massey Cancer Center, Medical College of Virginia, Richmond, VA.)

References

1. Schow DA, et al. South J Med 1998;91:855-857.

2. Veronesi A, et al. Tumori 1998;84:372-375.

3. Loprinzi CL, et al. J Clin Oncol 1998;16:2377-2381.

4. Loprinzi CL, et al. N Engl J Med 1994;331:347-352.

5. Quella SK, et al. Cancer 1998;82:1784-1788.

6. Barton DL, et al. J Clin Oncol 1998;16:495-500.

7. Lauffer LR, et al. Obstet Gynecol 1982;60:583-585.

8. Nagamani M, et al. Am J Obstet Gynecol 1987;156: 561-565.