Jeannette Y. Wick, RPh, MBA, FASCP
Ms. Wick is a senior clinical research
pharmacist at the National Cancer
Institute, National Institutes of
Health, Bethesda, Maryland. The
views expressed are those of the
author and not those of any government
During perimenopause, most
women experience hot flashes
of varying frequency and
intensity. When they occur more than a
few times daily, or even hourly, these
episodes can be quite disruptive and
are often accompanied by vaginal dryness,
decreased libido, forgetfulness,
difficulty concentrating, and night
sweats that disturb sleep.
Although estrogen and progesterone
are used to treat hot flashes, the
Women's Health Initiative (WHI) study
found that routine use of these therapies
increases some specific risks.1-3
Many women who had used estrogen
for hot flashes panicked and stopped
their medications abruptly, and now
those who might benefit from hormone
replacement therapy (HRT) are
searching for alternatives. For this reason,
pharmacists need to be fully
aware of self-care and medical treatment
options that can help women
manage menopausal symptoms.
Hot flashes usually subside over a
year or 2 after menopause, but in the
interim, these sudden sensations of
intense heat, frequently accompanied
by profuse sweating and facial or body
flushing, are intrusive and embarrassing.
The chill that follows can be terribly
uncomfortable. Stress, heavy alcohol
use, and cigarette smoking seem to
exacerbate hot flash frequency and
intensity. Sufferers may report anxiety,
irritability, or mild to severe heart palpitations.
Hot flashes can be especially
difficult for women who cease menstruating
abruptly from chemotherapy,
antiestrogen treatment for breast cancer,
or surgical removal of the ovaries.4
When to Treat
If hot flashes are mild or infrequent,
treatment is usually unnecessary.
Women who suffer moderate to severe
or frequent hot flashes often look for
relief, and some lifestyle choices may
help. Breathing exercises, for example,
have been shown to reduce hot flashes
and emotional symptoms significantly5,6(Table).
If hot flashes are severe and disruptive,
the patient may ask for medication.
Short-term HRT—at the lowest
dose needed for the shortest possible
time—remains the most effective
treatment. The WHI study linked HRT to
an increased risk of breast cancer, cardiovascular
disease, stroke, venous
thromboembolism, and dementia. It
also confirmed estrogen's protective
role in bone health.1-3
Pharmacists need to know that
treatment of menopausal symptoms
such as hot flashes was not a WHI end
point; WHI was designed to determine
if HRT prevents chronic diseases like
heart disease and osteoporosis. The
average age of WHI participants was
63, or about 12 years postmenopausal.
Since the study was published, it has
become more evident that depending
on the patient's age, hormone therapy
has different benefits and risks.7-11
Before menopause, estrogen?progestin
birth control pills can ameliorate
hot flashes and other perimenopausal
symptoms by preventing fluctuating
hormones. Perimenopausal women
who smoke, have diabetes, or have a
personal or family history of cardiovascular
disease or breast cancer should
avoid using estrogen for hot flash
Women who have an intact uterus
should not take unopposed estrogen;
they must also take progesterone.
Unopposed estrogen increases risk of
Interest in nonhormonal therapies is
high at this time. Selective serotonin
reuptake inhibitor (SSRI) antidepressant
medications can reduce the number
and severity of hot flashes;
researchers believe their ability to
inhibit serotonin reuptake may significantly
reduce vasomotor symptoms of
menopause. SSRIs are more likely to
work if the patient's main complaints
are hot flashes, irritability, or mood
swings. Pharmacists need to provide
the standard guidance about side
effects, counsel patients to take these
medications early in the day, especially
if insomnia is a problem, and advise
against abrupt discontinuation.15-20
Numerous studies have been conducted
using clonidine, which may
reduce peripheral vascular reactivity;
however, many of them are older,
small, or of poor design.21-25 To date, the
strongest evidence of clonidine's utility
is in women with tamoxifen-induced
hot flashes.21,25 Because hot flashes in
women with breast cancer are common
and pose a management problem
(estrogen therapy is contraindicated,
and tamoxifen interacts with many
drugs), this is an important option.
Black cohosh may reduce or prevent
hot flashes, depression, and anxiety,26,27 but a large, randomized, controlled,
placebo-blinded study (N = 351)
could not confirm its efficacy in either
premenopausal or postmenopausal
women.28 (This same study found no
benefit in soy supplements.) Although
most of this herb's side effects are mild
and transient (gastrointestinal upset or
rash), numerous studies and case
reports have documented black
cohosh's rare but potential hepatotoxicity,
which can cause death.29-33
Researchers recently have had encouraging
preliminary results with 49 g
of crushed flaxseed daily in a small study
(N = 30) of perimenopausal women,
noting reductions of >50% in hot flash
severity and frequency. Mild or moderate
abdominal distention was common,
as was mild diarrhea. This dietary therapy
needs more study to determine if it
is more effective than placebo.34
Although the number of alternative
treatments for hot flashes is increasing,
hormonal therapies are still the
most effective. Pharmacists need to be
familiar with the risks and benefits of
hormonal and nonhormonal therapies
and aware of the OTC products women
may use to find relief.
Clear communication about treatment
risks and benefits, individualization
of treatment to meet patient needs
and beliefs, and careful follow-up can
help women find potentially effective
therapy. The good news: Since the WHI
results were published, researchers
have documented a significant decrease
in prescriptions for HRT, but a significantly
higher percentage of prescription
filling. This seems to mean that
women who choose HRT do so with
greater certainty in their choice.35
- Anderson GL, Judd HL, Kaunitz AM, et al. Effects of estrogen plus progestin on gynecologic cancers and associated diagnostic procedures: the Women's Health Initiative randomized trial. JAMA. 2003;290:1739-1748.
- Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial. JAMA. 2002;288:321-333.
- Anderson GL, Limacher M, Assaf AR, et al. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial. JAMA. 2004;291:1701-1712.
- Obermeyer CM, Reher D, Saliba M. Symptoms, menopause status, and country differences: a comparative analysis from DAMES. Menopause. 2007;14:788-797.
- Irvin JH, Domar AD, Clark C, Zuttermeister PC, Friedman R. The effects of relaxation response training on menopausal symptoms. J Psychosom Obstet Gynaecol. 1996;17:202-207.
- Freedman RR, Woodward S, Brown B, Javaid JI, Pandey GN. Biochemical and thermoregulatory effects of behavioral treatment for menopausal hot flashes. Menopause. 1995;2:211-218
- Prentice RL, Langer RD, Stefanick ML, et al. Combined analysis of Women's Health Initiative observational and clinical trial data on postmenopausal hormone treatment and cardiovascular disease. Am J Epidemiol. 2006;163:589-599.
- Grodstein F, Manson JE, Stampfer MJ. Hormone therapy and coronary heart disease: The role of time since menopause and age at hormone initiation. J Womens Health. 2006;15:35-44.
- Manson JE, Allison MA, Rossouw JE, et al; WHI and WHI-CACS Investigators. Estrogen therapy and coronary-artery calcification. N Engl J Med. 2007;356:2591-2602.
- Anderson GL, Limacher M, Assaf AR, et al; Women's Health Initiative Steering Committee. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial. JAMA. 2004;291:1701-1712.
- Shumaker SA, Legault C, Kuller L, et al; Women's Health Initiative Memory Study. Conjugated equine estrogens and incidence of probable dementia and mild cognitive impairment in postmenopausal women: Women's Health Initiative Memory Study. JAMA. 2004;291:2947-2958.
- Panay N, Ylikorkala O, Archer DF, Gut R, Lang E. Ultra-low-dose estradiol and norethisterone acetate: effective menopausal symptom relief. Climacteric. 2007;10:120-131.
- Prior JC, Nielsen JD, Hitchcock CL, Williams LA, Vigna YM, Dean CB. Medroxyprogesterone and conjugated oestrogen are equivalent for hot flushes: a 1-year randomized double-blind trial following premenopausal ovariectomy. Clin Sci (Lond). 2007;112:517-525.
- Kaunitz AM. Oral contraceptive use in perimenopause. Am J Obstet Gynecol. 2001;185(2 Suppl):S32-S37.
- Stearns V, Beebe KL, Iyengar M, Dube E. Paroxetine controlled release in the treatment of menopausal hot flashes: a randomized controlled trial. JAMA. 2003;289:2827-2834.
- Gordon PR, Kerwin JP, Boesen KG, Senf J. Sertraline to treat hot flashes: a randomized controlled, double-blind, crossover trial in a general population. Menopause. 2006;13:568-575.
- Kerwin JP, Gordon PR, Senf JH. The variable response of women with menopausal hot flashes when treated with sertraline. Menopause. 2007;14:841-845.
- Loprinzi CL, Sloan JA, Perez EA, et al. Phase III evaluation of fluoxetine for treatment of hot flashes. J Clin Oncol. 2002;20:1578-1583.
- Loprinzi CL, Kugler JW, Sloan JA, et al. Venlafaxine in management of hot flashes in survivors of breast cancer: a randomised controlled trial. Lancet. 2000;356:2059-2063.
- Stearns V, Isaacs C, Rowland J, et al. A pilot trial assessing the efficacy of paroxetine hydrochloride (Paxil) in controlling hot flashes in breast cancer survivors. Ann Oncol. 2000;11:17-22.
- Pandya KJ, Raubertas RF, Flynn PJ, et al. Oral clonidine in postmenopausal patients with breast cancer experiencing tamoxifen-induced hot flashes: a University of Rochester Cancer Center Community Clinical Oncology Program study. Ann Intern Med. 2000;132:788-793.
- Edington RF, Chagnon JP, Steinberg WM. Clonidine (Dixarit) for menopausal flushing. Can Med Assoc J. 1980;123:23-26.
- Nagamani M, Kelver ME, Smith ER. Treatment of menopausal hot flashes with transdermal administration of clonidine. Am J Obstet Gynecol. 1987;156:561-565.
- Nappi C, Petraglia F, de Chiara BM, et al. The effect of various drugs with neuroendocrine activity and transdermal estradiol on plasma gonadotropin concentrations after ovariectomy in reproductive-aged women. Acta Obstet Gynecol Scand. 1991;70:435-439.
- Goldberg RM, Loprinzi CL, O'Fallon JR, et al. Transdermal clonidine for ameliorating tamoxifen-induced hot flashes. J Clin Oncol. 1994;12:155-158. [Erratum appears in J Clin Oncol. 1996;14:2411]
- Oktem M, Eroglu D, Karahan HB, Taskintuna N, Kuscu E, Zeyneloglu HB. Black cohosh and fluoxetine in the treatment of postmenopausal symptoms: a prospective, randomized trial. Adv Ther. 2007;24:448-461.
- McKenna DJ, Jones K, Humphrey S, Hughes K. Black cohosh: Efficacy, safety, and use in clinical and preclinical applications. Alter Ther Health Med. 2001;7:93-100.
- Newton KM, Reed SD, LaCroix AZ, Grothaus LC, Ehrlich K, Guiltinan J. Treatment of vasomotor symptoms of menopause with black cohosh, multibotanicals, soy, hormone therapy, or placebo: a randomized trial. Ann Intern Med. 2006;145:869-879.
- Levitsky J, Alli TA, Wisecarver J, Sorrell MF. Fulminant liver failure associated with the use of black cohosh. Dig Dis Sci. 2005;50:538-539.
- Lynch CR, Folkers ME, Hutson WR. Fulminant hepatic failure associated with the use of black cohosh: a case report. Liver Transpl. 2006;12:989-992.
- Whiting PW, Clouston A, Kerlin P. Black cohosh and other herbal remedies associated with acute hepatitis. Med J Austr. 2002; 177:440-443.
- Verma S, Thuluvath PJ. Complementary and alternative medicine in hepatology: review of the evidence of efficacy. Clin Gastroenterol Hepatol. 2007;5:408-416.
- Dunbar K, Solga SF. Black cohosh, safety, and public awareness. Liver Int. 2007;27:1017-1018.
- Pruthi S, Thompson SL, Novotny PJ, et al. Pilot evaluation of flaxseed for the management of hot flashes. J Soc Integr Oncol. 2007;5:106-112.
- Parente L, Uyehara C, Larsen W, Whitcomb B, Farley J. Long-term impact of the women's health initiative on HRT. Arch Gynecol Obstet. 2007;[Epub ahead of print].