Relieving Menopausal Symptoms with Black Cohosh and Soy
Many women are turning to dietary supplements for relief of menopausal symptoms, and pharmacists are in a prime position to advise them on their appropriate use.
Dr. Brown is an assistant professorof pharmacy practice at Palm BeachAtlantic University, Lloyd L. GregorySchool of Pharmacy, West Palm Beach,Florida.
Menopause occurs when theovaries no longer produceestrogen, a process thatbegins in a woman's mid-30s withalmost complete cessation of estrogenproduction by her mid-50s. Menopauseis defined as the cessation of mensesfor at least 12 consecutive months.Undergoing surgical procedures (eg,hysterectomies), chemotherapy, andirradiation can induce the immediateonset of menopause.
Though menopause is a normal partof the aging process for most women,this change can have physical and psychologicalimplications. In fact, up to85% of women experience menopausalsymptoms, including hot flushes, nightsweats, insomnia, and vaginal drynessthat can lead to painful sexual intercourse.1 Additionally, concomitant depressionand anxiety may stem fromthis biological process. Thus, it is notsurprising that many women will seekmedical advice for the alleviation ofthese symptoms as they can have a significantimpact on their quality of life.
In addition to nonpharmacologic recommendations,such as smoking cessation,increased physical activity, andminimizing alcohol intake, hormonereplacement therapy (HRT) is perhapsthe most effective therapy for the reliefof the aforementioned menopausalsymptoms.1 In light of data that suggesta potential increased risk for cancer, cardiovasculardisease, and venous thromboembolism(VTE), however, manywomen are hesitant to begin HRT.2-5
Many women prefer a more naturalapproach to treatment and are turningto the use of dietary supplements forthe relief of menopausal symptoms. Onesmall study showed that women whoused dietary supplements as part of themanagement of menopause, either asmonotherapy or in combination withHRT, reported overall control of theirmenopausal symptoms and an improvedquality of life.6
Pharmacists are in the prime positionto advise patients on the appropriate useof these supplements for symptom alleviation.Though many complementaryalternative medicine options exist, someproducts that commonly are sought outby women to treat menopausal symptomsinclude black cohosh, soy, dongquai, ginseng, vitamin E, red clover, andkava. This article focuses on the use ofblack cohosh and soy.
Black Cohosh (Actaea racemosa)
Studies suggest that black cohoshappears to reduce menopausal symptomsmodestly, especially hot flushes.7,8One 3-month study found that 40 mg/day of black cohosh was similar in hotflush reduction, compared with transdermalestradiol 25 mcg applied weekly.Effects were seen by the first month andmaintained throughout the remainder ofthe study.8
Additionally, the use of black cohoshin combination with St. John's worthas shown improvements in both hotflush complaints and depressive symptoms.9 Although most studies have onlyassessed the safety and efficacy of blackcohosh for up to 6 months, 2 studiesdemonstrated the safe use of blackcohosh supplements for up to 1 year.10,11
Black cohosh appears to be effectivein the treatment of menopausal symptomsby acting like an estrogen receptormodulator, producing estrogenic effectson bone, but causing antiestrogeniceffects on other tissues. One animalstudy suggests that black cohosh doesnot increase the risk for breast cancer;however, it increased the risk for metastaticcancer in those animals with existingcancer.12
Conflicting data exist on whetherblack cohosh is safe and effective forthe alleviation of hot flushes in womenwho are breast cancer survivors.13-15Though black cohosh does not appearto affect estrogen receptors, the use ofthe supplement has not been studied inlong-term trials, and therefore, the use ofblack cohosh?containing products is notrecommended in women with hormone-sensitivecancers, such as breast, uterine,and ovarian.
Common adverse effects reportedwith black cohosh are gastrointestinal(GI) upset, abdominal pain, breast tenderness,and vaginal spotting or bleeding.16-18 A rare but serious potentialadverse effect is hepatitis. Thus, routineassessment of liver function is advised.19It is also important to note that blackcohosh should not be confused withblue or white cohosh.
Research suggests that black cohoshmodestly inhibits the cytochrome P450isoenzyme 2D6.20 Drugs such as amitriptyline,haloperidol, paroxetine, andondansetron, among others, are metabolizedthrough this isoenzyme, and concentrationsmay be prolonged with concomitantadministration of black cohosh.Caution is warranted with concomitantuse of these agents.
Women electing to use black cohoshalso should be counseled that immediaterelief of symptoms should not beexpected, and it can take up to 4 weeksto see effects.8
The effects of soy on relieving hot flusheshave been investigated after recognizingthat Asian women who typically havea diet high in soy reported lower ratesof hot flushes, compared with Americanwomen. Soy contains isoflavones, a typeof phytoestrogen that possesses weakestrogenic activity to relieve hot flushes.1Clinical data show conflicting results onthe efficacy of soy to minimize menopausalsymptoms, however.11,21-24 One6-month trial comparing 0.625 mg dailyof conjugated equine estrogens witha standardized isoflavone-containingproduct demonstrated similar efficacybetween the 2 products.25
The average dose of isoflavones studiedhas ranged from 40 to 80 mg daily.Though many foods such as soy milk,soy sauce, and soy nuts contain isoflavones,supplementation is typicallyrequired to achieve maximum benefits.1This is because approximately 1 g of soyonly contains between 1.2 and 1.7 mg ofisoflavones, which is much less than thestudied amounts of 40 to 80 mg daily.
The most common adverse effect isGI distress, including diarrhea, nausea,bloating, and constipation.26 Due toestrogenic effects, concern exists aboutsoy's potential to increase the risk forbreast and endometrial cancers. Thisconcern is validated as findings froma 5-year study of isoflavones suggest apotential risk for endometrial cancer.27Therefore, similar to black cohosh, theuse of soy in patients with a history ofhormone-sensitive cancers is not recommended.1
Patients may ask if the use of soyincreases the risk for VTE, especially inlight of the risk associated with estrogentherapy. Currently data do not suggestthat soy has any effects on coagulationor fibrinolysis.28
Drug interactions are also an importantconsideration when counselingpatients on these products. Normal gutflora is partially responsible for convertingisoflavones to more biologicallyactive components. Thus, antibiotics thatwipe out gut flora reduce the efficacyof soy-containing products, decreasingthe efficacy of soy during this time andfollowing completion of the antibioticuntil regeneration of gut flora occurs.29Additionally, information from a casereport of a patient receiving warfarin andconsuming soy milk found the internationalnormalized ratio was reduced.30Thus, close monitoring of patients onwarfarin using soy supplements is warranted,especially with initiation andtitrations.
Role of the Pharmacist
Dietary supplements commonly aresought out by patients for various reasons.As they are available over thecounter, patients may believe the use ofherbal products is undoubtedly safe. Asa pharmacist, it is prudent to assess eachpatient's symptoms, ask about medicalconditions and current medications,as well as consider a patient's allergyinformation, prior to making a recommendation.
Neither black cohosh nor soy shouldbe recommended in women with ahistory of hormone-sensitive cancers.Additionally, both agents have potentialdrug?drug interactions that will likelymerit close monitoring. Thus, basicknowledge about common herbals, suchas black cohosh and soy, that are usedfor the management of menopausalsymptoms is imperative to optimizingpatient outcomes.
- AACE Menopause Guidelines Revision Task Force. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the diagnosis and treatment of menopause. Endocr Pract. 2006;12(3):315-337.
- Cushman M, Kuller LH, Prentice R, et al. Estrogen plus progestin and risk of venous thrombosis. JAMA. 2004(13);292:1573-1580.
- Manson JE, Hsia J, Johnson KC, et al. Estrogen plus progestin and risk of coronary heart disease. N Engl J Med. 2003;349(6):523-534.
- Chlebowski RT, Hendrix SL, Langer RD, et al. Influence of estrogen and progestin on breast cancer and mammography in healthy post-menopausal women: The Women?s Health Initiative randomized trial. JAMA. 2003;289(24):3243-3253.
- Barnabei WM, Grady D, Stovall DW, et al. Menopausal symptoms in older women and the effects of treatment with hormone therapy. Obstet Gynecol. 2002;100(6):1209-1218.
- Kam IW, Dennehy CE, Tsourounis C. Dietary supplement use among menopausal women attending a San Francisco health conference. Menopause. 2002;9(1):72-78.
- Osmers R, Friede M, Liske E, et al. Efficacy and safety of isopropanolic black cohosh extract for climacteric symptoms. Obstet Gynecol. 2005;105(5 Pt 1)1074-1083.
- Nappi RE, Malavasi B, Brundu B, Facchinetti F. Efficacy of Cimicifuga racemosa on climacteric complaints: a randomized study versus low-dose transdermal estradiol. Gynecol Endocrinol. 2005;20(1):30-35.
- Uebelhack R, Blohmer JU, Graubaum HJ, et al. Black cohosh and St. John's wort for climacteric complaints: a randomized trial. Obstet Gynecol. 2006;107(2 Pt 1):247-255.
- Raus K, Brucker C, Gorkow C, Wuttke W. First-time proof of endometrial safety of the special black cohosh extract (Actaea or Cimicifuga racemosa extract) CR BNO 1055. Menopause. 2006;13(4):678-691.
- Newton KM, Reed SD, LaCroix AZ, Grothaus LC, Ehrlich K, Guiltinan J. Treatment of vasomotor symptoms of menopause with black cohosh, mulitbotanicals, soy, hormone therapy, or placebo. Ann Intern Med. 2006;145(12)869-879.
- Seidlova-Wuttke D, Hesse O, Jarry H, et al. Evidence for selective estrogen receptor modulator activity in a black cohosh (Cimicifuga racemosa) extract: comparison with estradiol-17beta. Eur J Endocrinol. 2003;149(4):351-362.
- Davis VL, Jayo MJ, Hardy ML, et al. Effects of black cohosh on mammary tumor development and progression in MMTV-neu transgenic mice. Presented at: Annual Meeting of the American Association for Cancer Research; July 11-14, 2003; Washington, DC. Abstract R910.
- 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(10):2739-2745.
- Hernandez Munoz G, Pluchino S. Cimicifuga racemosa for the treatment of hot flushes in women surviving breast cancer. Maturitas. 2003;44(suppl 1):S59-S65.
- Pockaj BA, Gallagher JG, Loprinzi CL, et al. Phase III double-blind, randomized, placebo-controlled crossover trial of black cohosh in the management of hot flashes: NCCTG Trial N01CC1. J Clin Oncol. 2006;24(18):2836-2841.
- Bai W, Henneicke-von Zepelin HH, Wang S, et al. Efficacy and tolerability of a medicinal product containing an isopropanolic black cohosh extract in Chinese women with menopausal symptoms: a randomized, double blind, parallel-controlled study versus tibolone. Maturitas. 2007;58(1):31-41.
- Pepping J. Black cohosh: Cimicifuga racemosa. Am J Health Syst Pharm. 1999;56(14):1400-1402.
- Whiting PW, Clouston A, Kerlin P. Black cohosh and other herbal remedies associated with acute hepatitis. Med J Aust. 2002;177(8):440-443.
- Gurley BJ, Gardner SF, Hubbard MA, et al. In vivo effects of goldenseal, kava kava, black cohosh, and valerian on human cytochrome P450 1A2, 2D6, 2E1, and 3A4/5 phenotypes. Clin Pharmacol Ther. 2005;77(5):415-426.
- Han KK, Soares JM Jr, Haider MA, de Lima GR, Baracat EC. Benefits of soy isofalvone therapeutic regimen on menopausal symptoms. Obstet Gynecol. 2002;99(3):389-394.
- Quella SK, Loprinzi CL, Barton DL, et al. Evaluation of soy phytoestogens for the treatment of hot flashes in breast cancer survivors: A North Central Cancer Treatment Group Trial. J Clin Oncol. 2000;18(5):1068-1074.
- Van Patten CL, Olivotto IA, Chambers GK, et al. Effect of soy phytoestrogens on hot flashes in postmenopausal women with breast cancer: a randomized controlled clinical trial. J Clin Oncol. 2002;20(6):1449-1455.
- Huntley AL, Ernst E. Soy for the treatment of perimenopausal symptoms–a systematic review. Maturitas. 2004;47(1):1-9.
- Kaari C, Haidar MA, Junior JMS, et al. Randomized clinical trial comparing conjugated equine estrogens and isoflavones in postmenopausal women: a pilot study. Maturitas. 2006;53(1):49-58.
- Albertazzi P, Pansini F, Bonaccorsi G, et al. The effect of dietary soy supplementation on hot flushes. Obstet Gynecol. 1998;91(1):6-11.
- Unfer V, Casini ML, Costabile L, et al. Endometrial effects of long-term treatment with phytoestrogens: a randomized, double-blind, placebo-controlled study. Fertil Steril. 2004;82(1):145-148.
- Teede HF, Dalais FS, Kotsopoulos D, et al. Dietary soy containing phytoestrogens does not activate the hemostatic system in postmenopausal women. J Clin Endocrinol Metab. 2005;90(4):1936-1941.
- Morito K, Hirose T, Kinjo J, et al. Interaction of phytoestrogens with estrogen receptors alpha and beta. Biol Pharm Bull. 2001;24(2):351-356.
- Cambria-Kiely JA. Effect of soy milk on warfarin efficacy. Ann Pharmacother. 2002;36(12):1893-1896.