Treating hot flushes without hormone replacement therapy

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Applied Evidence

Treating hot flushes without hormone replacement therapy

J Fam Pract. 2003 April;52(4):291-296

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References

1. Salamone LM, Pressman AR, Seeley DG, Cauley JA. Estrogen replacement therapy. A survey of older women’s attitudes. Arch Int Med 1996;156:1293-1297.

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5. Grady D, Herrington D, Bittner V, et al. Cardiovascular disease outcomes during 6.8 years of hormone replacement therapy: Heart and Estrogen/progestin Replacement Study follow-up (HERS II). JAMA 2002;288:49-57.

6. Seibel MM. The role of nutrition and nutritional supplements in women’s health. Fertil Steril 1999;72:579-591.

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11. Murkies AL, Lombard C, Strauss BJD, Wilcox G, Burger HG, Morton MS. Dietary flour supplementation decreases postmenopausal hot flushes: effect of soy and wheat. Maturitas 1995;21:189-195.

12. Brzezinski A, Adlercreutz H, Shaoul R, Rosler A, Shmueli A, Tanos V, Schenker JG. Short-term effects of phytoestrogen-rich diet on postmenopausal women. Menopause 1997;4:89-94.

13. Albertazzi P, Pansini F, Bonaccorsi G, Zanotti L, Forini E, De Aloysio D. The effect of dietary soy supplementation on hot flushes. Obstet Gynecol 1998;91:6-11.

14. Scambia G, Mango D, Signorile PG, et al. Clinical effects of a standardized soy extract in postmenopausal women: a pilot study. Menopause 2000;7:105-111.

15. Upmalis DH, Lobo R, Bradley L, Warren M, Cone FL, Lamia CA. Vasomotor symptom relief by soy isoflavone extract tablets in postmenopausal women: a multicenter, double-blind, randomized, placebo-controlled study. Menopause 2000;7:236-242.

16. Kronenberg F, Fugh-Berman A. Complementary and alternative medicine for menopausal symptoms: a review of randomized, controlled trials. Ann Intern Med 2002;137:805-811.

17. Shaver JLF, Giblin E, Paulsen V. Sleep quality subtypes in midlife women. Sleep 1991;14:18-23.

18. From Seibel MM. The soy solution for menopause: an alternative to estrogen. New York, NY: Fireside Press, 2003.

19. Struck D, Tegtmeier M, Harnishfeger G. Flavones in extracts of Cimicifuga racemosa. Planta Med 1997;63:289-290.

20. Beuscher N. Cimicifuga racemosa L.Black Cohosh. HerbalGram 1996;19-27.

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23. Stoll W. Phytopharmacon influences atrophic vaginal epithelium: double-blind study—Cimicifuga vs. estrogenic substances. Therapeuticum 1987;1:23-31.

24. Jacobson JS, Troxel AB, Evans J, et al. Randomized trial of black cohosh for the treatment of hot flashes among women with a history of breast cancer. J Clin Oncol 2001;19:2739-2745.

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Clinical efficacy

Hot flushes. An increasing number of studies suggest that soy and soy isoflavones—in the form of soy flour, soy protein, and dietary supplements—may play an important role in the treatment of hot flushes. In general, the average amount of isoflavones consumed in a typical Asian diet is approximately 50 mg/day. (One gram of soy protein contains approximately 1 mg of isoflavones.)

Unfortunately, clinical trial data are confounded by varying preparations of soy, length of therapy, outcomes measured, and small sample sizes. The absolute risk reduction of soy preparations versus placebo or comparators in positive trials ranges from 10% to 20% (number needed to treat [NNT]=6–10) when frequency of hot flushes is the outcome measured (Table 1).^11-15

Placebo effect. All soy studies also confirm the existence of a placebo effect on the treatment of hot flushes. The large placebo effect and varied efficacy has left many skeptics questioning the clinical efficacy of soy products.¹⁶

I believe that thinking is wrong. Women who have hot flushes tend to have lower sleep efficiencies and longer REM latencies than women who do not experience this vasomotor symptom.¹⁷ By lowering the frequency of hot flushes, soy may produce greater sleep efficiencies and improve quality of life.

TABLE 1
Positive trials* of soy in the treatment of hot flushes

Absolute risk reduction of hot flushes (%)
Study	N	Design	Soy	Control	NNT	LOE^†
Murkies 1995¹¹	58	45 g soy flour	42	25	6	1b
Brzezinski 1997¹²	73/72	Mostly soy, 1/4 diet, some flaxseed	54	35
Albertazzi 1998¹³	51/53	60 g soy protein	43.6	31.3	8.1	2b
Scambia 2000¹⁴	39	50 mg/d isoflavones	45	25	1b
Upmalis 2000¹⁵	177	50 mg/d isoflavones	30	20	1b
From Seibel MM, The soy solution for menopause: an alternative to estrogen. New York, NY: Fireside Press, 2003.
*None of the above trials were of high quality—all either had a large number of dropouts, substantial divergence of outcomes, a small “n” (number of subjects) or other substantive methodological concerns.
NNT, number needed to treat; LOE, level of evidence
†See page 290 for a description of strength of recommendation.

Safety

Soy has been safely consumed by hundreds of millions of people without complications, with t he possible exception of soy allergies (Table 2). The literature suggests it is safe and effective in dosages of either 40 g of soy protein or 50 mg of soy isoflavones per day. Soy does not stimulate the uterine lining and may be protective of the endometrium if taken with estrogen.

The incidence of breast cancer is one fourth as high in Asia as in the US; many studies have shown soy to be protective of breast tissue. However, soy may stimulate breast tissue in women with a history of breast cancer. The evidence in these areas is conflicting and controversial.

In contrast to herbal alternatives to HRT, soy has been thought to lower cholesterol, make blood vessels more elastic (increase vascular elasticity), and slow osteoclast activity in bones. It is also an excellent source of protein, and is lactose- and cholesterol-free.¹⁸

TABLE 2
Remedies for hot flushes and their adverse effects, interactions, and contraindications

	Adverse effects	Important drug interactions	Contraindications
Soy	Bloating, flatulence	Thyroid hormone, if taken simultaneously	Use with caution in patients being treated for hypothyroidism (soy may bind thyroid medication, thus lowering absorption; patients on thyroid hormone should use soy only in supplement form or take at a time distant from thyroid medication)
Black cohosh	Abdominal pain, nausea, headaches, dizziness, trembling limbs	Iron therapy medications	Patients with iron deficiencies; use cautiously in patients with breast cancer or high risk of breast cancer
Dong quai	Photodermatitis, rash	Warfarin (effects potentiated)	Patients with coagulopathies or very heavy menstruation and acute viral infections such as colds or influenza; pregnancy
Evening primrose oil	Nausea, softening of stools, headaches, seizures	Anticonvulsant and tricyclic antidepressants	Patients taking anticonvulsants and tricyclic antidepressants (lowers efficacy)
Red clover	Blood thinning	Anticoagulants such as coumadin, heparin, clopidrogel, pentoxifylline, or aspirin	Patients with coagulopathies

Black cohosh

A member of the buttercup family, black cohosh (Actaea [formerly Cimicifuga] racemosa) has a long history in folk medicine, especially among Native Americans, who boiled the root in water and drank the resulting beverage to treat dysmenorrhea, labor pain, upset stomach, and arthritis. In Germany, extracts of black cohosh have been used since the 1940s.

Many substances have been identified in the rhizome, but it is uncertain what the majority of them do or, in fact, which are active ingredients.¹⁹ The effectiveness of black cohosh is based on the total amount of triterpenoid glycosides, typically standardized to 2.5%.²⁰

Several studies, most of them in the German literature, have shown that black cohosh yields a significant improvement in hot flushes, with reductions of up to 80% reported (level of evidence [LOE]: 2b).^21-23 The usual dosage is 40 drops of the extract twice daily for 6 to 8 weeks, or one to two 20-mg tablets twice daily with liquid (not to be chewed or sucked).