Marcia Phillips, DNSc, RN Young-Me Lee, MSN, RN Barbara Swanson, DNSc, RN Joyce K. Keithley, DNSc, RN, FAAN Janice M. Zeller, PhD, RN, FAAN Patricia

Transcription

1 Marcia Phillips, DNSc, RN Young-Me Lee, MSN, RN Barbara Swanson, DNSc, RN Joyce K. Keithley, DNSc, RN, FAAN Janice M. Zeller, PhD, RN, FAAN Patricia Hindin, MSN, RN, CNM

2 With the latest findings from the Women s Health Initiative confirming what made headline news in 2002 that hormone therapy (HT) is now more of a presumed harm than potential benefit, particularly for women with or at risk for cardiovascular disease or cancer (Herrington & Howard, 2003), women are increasingly turning to alternative therapies to treat the signs and symptoms of menopause. Concerns about side effects and long-term risks of HT, interest in using more natural approaches to maintain health, and extensive media coverage are among the factors that have contributed to the increased use of alternative therapies. Until recently, HT (estrogen with or without progestin) was widely prescribed to treat menopausal symptoms and to prevent chronic conditions such as osteoporosis and heart disease. However, this practice has been called into question by recent findings suggesting that HT should be used with great caution as the harms outweigh the benefits for many women (Chlebowski et al., 2003; Grady et al., 2002; Hulley et al., 2002; Rossouw et al., 2002).

3 Not surprisingly, many menopausal women are beginning to use alternative therapies, such as herbal and dietary supplements, to alleviate their symptoms. A common assumption about herbal and dietary therapies is that they are natural and therefore safe and effective. Herbal and dietary supplements can, however, vary in concentration of active ingredients among different brands and within different lots of the same brand, may be contaminated or adulterated with toxic agents such as pesticides and heavy metals, or have adverse effects and toxicities. For example, recent concerns about ephedra, a Chinese herb known as ma huang, and it s potentially dangerous effects on the nervous system and heart underscore the need for caution (Cockey, 2003). Herbal and dietary therapies can also interact with prescription medications. For example, gingko, garlic, and ginseng can inhibit platelet aggregation and increase risk of bleeding in persons taking anticoagulants; St. John s wort can decrease plasma concentrations of protease inhibitors, steroids, and coumadin (Kelly, 2001). Nurses need to understand the potential risks and benefits of herbal and dietary supplements for menopause symptoms as well as promote their safe and effective use when indicated (see Box 1). The most common menopausal symptom for which women are using herbal and dietary supplements is hot flashes. In this review, mechanisms of action and evidence supporting the potential benefits and risks of herbal and dietary supplements are described, and clinical implications are proposed. HOT FLASHES Hot flashes are the major complaint of women going through menopause. Linked to declining levels of estrogen, hot flashes may affect 80 percent of menopausal women. The cause of vasomotor symptoms (hot flashes and night sweats) is only partly understood. Hot flashes are a sudden intense response of the body s normal cooling system that is activated when the body becomes overheated. Blood vessels near the skin surface dilate to dissipate the heat, which causes the body to break out in a sweat. Body temperature is regulated in the hypothalamus, Marcia Phillips, DNSc, RN, is assistant professor, health systems management, Rush University College of Health Sciences in Chicago, IL. Young-Me Lee, MSN, RN, is a doctoral student at Rush University College of Nursing. Barbara Swanson, DNSc, RN, is assistant professor, adult health nursing, at Rush University College of Nursing. Joyce K. Keithley, DNSc, RN, FAAN, is professor, adult health nursing, at Rush University College of Nursing. Janice M. Zeller, PhD, RN, FAAN, is professor, adult health nursing, Rush University College of Nursing. Patricia Hindin, MSN, RN, CNM, is a doctoral student at Rush University College of Nursing. DOI: / but it s not known how an estrogen decline influences this regulatory center (Dormire, 2003). Anecdotal evidence has been suggested for a number of self-help measures to relieve hot flashes and sweats, including (Brucker & Youngkin, 2002): wearing light clothing dressing in layers lowering room temperature drinking cold beverages In addition, deep breathing techniques used in yoga have been found to be beneficial. Avoiding caffeinated beverages, chocolate, spicy foods, alcohol, and hot foods may also provide relief (Shaw, 1997). Herbs & Supplements for Hot Flashes Several of the more commonly used herbal and dietary supplements for the management of hot flashes include (Brucker & Youngkin, 2002): black cohosh soy products dong quai vitamin E BLACK COHOSH Black cohosh (Cimicifuga racemosa) is a perennial plant native to the eastern parts of North America. Native Americans have traditionally used it for menstrual and menopausal symptoms. Approved in 1989 by the German regulating division for herbal products, Commission E, it has become the leading herb for relief of menstrual symptoms in Germany and has been used in many other parts of Europe as well (Blumenthal, 1998). However, few randomized controlled studies have been conducted to test the effectiveness of this herb in the treatment of hot flashes. Mechanism of action. Black cohosh has been reported to have luteinizing hormone (LH) suppressive effects (Pepping, 1999), but it does not influence endometrial thickness, vaginal maturation index or levels of follicle stimulating hormone (FSH), estradiol, estrone, prolactin or sex hormone binding globin (Liske, 1998). Evidence. In a randomized, placebo-controlled trial conducted in women who had been treated for breast cancer, 60 days of black cohosh therapy resulted in some decline in number and intensity of hot flashes; however, this change was not significantly different from the control group (Jacobson et al., 2001). The only symptom that significantly decreased was sweating, but this decrease was comparable in both groups. Other clinical studies of black cohosh are inconclusive. Methodology issues, such as the lack of control groups, use of different types and doses of black cohosh, inappropriate com- 416 AWHONN Lifelines Volume 7 Issue 5

4 parison treatments or short study duration (8 to 24 weeks), make it difficult to draw conclusions from the studies findings (Kronenberg & Fugh-Berman, 2002; NCCAM, 2003). Although long-term safety and efficacy data are unavailable, a 12-month controlled study of the effectiveness of black cohosh in reducing the severity and frequency of hot flashes is currently under way (NCCAM, 2003). Adverse effects. Adverse effects include minor gastrointestinal discomfort, weight gain, hypotension and headache. Large doses have been associated with miscarriages. Overdose can cause nausea/vomiting, dizziness, visual disturbance and/or bradycardia. A German study found no evidence for toxic or mutagenic effects in animals after the administration of extract for six months at 90 times the human dose (Beuscher, 1995). Although it remains controversial as to whether black cohosh has estrogenic properties, it s not recommended for use in pregnant women and should be avoided with estrogenresponsive conditions. Also, it should not be used in combination with estrogen therapy, anticoagulants and antihypertensives. Quality and purity may vary among preparations; however, the majority of clinical trials used the same brand (Remifemin ). SOY PRODUCTS Soy products such as soymilk, tofu and soy nuts are considered to have phytoestrogenic properties. Phytoestrogens are nonsteroidal compounds from plants that can have estrogenic or antiestrogenic effects. Commonly ingested phytoestrogens include isoflavones, lignans, and coumestrans. Soy products are particularly rich in isoflavones, primarily genistein and daidzein. Mechanism of action. Phytoestrogens, such as those found in soy and certain other natural products including red clover, bind to the selective estrogen receptor modulators and serve as estrogen antagonists when there is a high concentration of estrogen. But in an environment of low estrogen concentrations, phytoestrogens serve as weak agonists by stimulating the estrogen receptors. Evidence. There is no consistent evidence that soy products reduce hot flashes in postmenopausal women. While two earlier studies showed a beneficial effect (Albertazzi et al., 1998; Scambia et al., 2000), a recent randomized, controlled clinical trial that compared a high-concentration soy beverage to a placebo in postmenopausal women experiencing hot flashes showed no significant difference between the two groups. In this trial, both groups had significant reductions of hot flashes over time, presumably due to a placebo effect (Van Patten et al., 2002). Other studies have shown similar placebo effects, ranging from 20 to 30 percent reductions in frequency and severity of hot flashes (Sloan et al., 2001). Studies of longer duration and comparisons of intact soy protein and soy isolates are needed to elucidate whether soy products are safe or have any beneficial effects in managing hot flashes. Adverse effects. In general, phytoestrogens from dietary sources have few adverse effects, with the exception of gastrointestinal disturbances and allergic reactions in sensitive individuals. Concentrated isoflavones, packaged and sold as supplements, are not recommended for persons with hormonedependent tumors. This is due to selective estrogen receptor stimulation, which could possibly lead to promotion of estrogen-dependent tumor growth, although research is inconclusive. Phytoestrogen supplements should also be avoided in women with breast, ovarian or endometrial cancer or a strong family history of cancer. Those undergoing estrogen replacement therapy or taking tamoxifen should also be cautioned regarding the use of phytoestrogens. Since soy may reduce thyroid hormone synthesis, it should be avoided in persons with thyroid disorders until research clarifies this risk for potential harm. Furthermore, the safety of soy supplements has not been tested in pregnant or lactating women. DONG QUAI Dong quai (Angelica sinensis) is a traditional Chinese medicine herb generally used in combination with other herbs treating Box 1. Recommending Herbs & Dietary Supplements Wisely Nurses can promote the safe and effective use of herbal and dietary supplements by: staying abreast of new information about the safety and efficacy of herbal and dietary therapies carefully eliciting herbal and dietary supplement use during history taking communicating effectively about the risks and benefits of these therapies for treating menopausal symptoms referring patients to reliable alternative therapy resources October November 2003 AWHONN Lifelines 417

5 hot flashes, dysmenorrhea, irregular menses or breast tenderness. It s an aromatic herb and is also used to flavor candy liqueurs. The dried root and liquid extract are the most commonly used parts of the plant. Mechanism of action. Coumarin derivatives are believed to be the active ingredients of this herb. Coumarins act as vasodilators and antispasmodics. Dong quai is also thought to contain phytoestrogens; however, not all studies would support this conclusion. Evidence. A double-blind placebo-controlled study (Hiruta, Swierz, Zell, Small, & Ettinger, 1997) showed no statistically significant difference between dong quai (4.5 g daily) and placebo use on estrogen levels, endometrial thickness, vaginal cytology or menopausal symptoms among 71 women. There is no clear evidence supporting the use of dong quai as a monotherapy for treatment of hot flashes. In traditional Chinese medicine, dong quai is usually administered in combination with other herbs. Alternative medicine practitioners argue that the herbal preparation needs to be individualized for maximal efficacy. This is perhaps why, when tested alone, dong quai has not been proven to have an effect on the occurrence of hot flashes. Additional clinical studies of dong quai, alone and in combination with other herbs, are needed to provide more evidence for its effects on hot flashes. Adverse effects. If applied externally, dong quai can cause photodermatitis and phototoxicity. One active ingredient, furanocoumarin bergapten, may have carcinogenic properties. Coumarin components should not be used in conjunction with other blood thinners such as warfarin, aspirin or coumarin. Dong quai is not recommended for women with excessive menstrual flow, those with fibroids, or fever. Since it contains a high level of sucrose, diabetics also should avoid this product. VITAMIN E Vitamin E is a fat-soluble vitamin found in many foods. While it exists in numerous forms in food products, the most common supplementary preparation of vitamin E is alphatocopherol. Vitamin E is used as a supplement, largely due to its antioxidant properties. Mechanism of action. Vitamin E protects polyunsaturated fatty acids in cell membranes and plasma lipoproteins from oxidative damage. It helps regulate vascular smooth muscle cell proliferation and inhibits low-density lipoprotein (LDL) oxidation. Also as an anticoagulant, Vitamin E plays a role in the inhibition of platelet aggregation. Evidence. Because early evidence indicated that vitamin E is essential for normal reproduction, it was initially used for recurrent spontaneous abortions and ultimately for other female disorders such as menstrual and menopausal symptoms. There are very few studies regarding the use of vitamin E alone for hot flashes. A placebo-controlled, randomized, crossover clinical trial with 120 breast cancer survivors compared 800 IU of vitamin E daily to placebo for the reduction of hot flashes. There was only a marginal difference between groups. Vitamin E was associated with one less hot flash per day compared to the placebo, a finding which did not translate into a higher degree of satisfaction in the treatment group (Barton et al., 1998). Few studies have been conducted to evaluate the use of vitamin E to control hot flashes. In a study of breast cancer survivors, a group with a high prevalence of hot flashes, vitamin E supplements reduced hot flashes by only one per week (Barton et al., 1998). There have been no controlled trials on the effects of vitamin E supplements to manage hot flashes in healthy menopausal women. Adverse effects. Vitamin E supplementation has been associated with gastrointestinal disturbances, rashes and fatigue. It also may enhance the effects of anticoagulants and interfere with the lipid-reducing effects of statins. Vitamin E, at a moderate dose (800 IU/day), when compared to placebo in a crossover analysis of 105 breast cancer survivors, was not associated with any toxicities over a four-week period of time (Barton et al., 1998). 418 AWHONN Lifelines Volume 7 Issue 5

6 Table 1. Information on Menopause Supplements Supplement How It Works Adverse Effects Known Drug Interactions Nursing Implications Black Cohosh Exerts estrogen- GI disturbances, Anticoagulants: Caution patients with estrogenlike effects hypotension, headache, Potential for bleeding sensitive conditions to avoid use through weight gain, dizziness events (e.g., breast, uterine or ovarian unknown cancer; endometriosis; uterine mechanism Antihypertensives: fibroids) Potential for increased hypotensive effects Soy Soy isoflavones GI disturbances, hyper- Conjugated estrogens: Caution against use of suppleare structurally sensitivity reactions in Potential additive or mental soy in persons with persimilar to estra- sensitive persons competitive effect sonal or family history of breast diol and can cancer, thyroid disease or women bind to estrogen Thyroid hormones: who are pregnant or lactating receptors Reduced absorption when given with soy Advise asthmatics to avoid soy products as they are often Tamoxifen: allergic to soy husks Potential for antagonism of antiestrogenic effect of tamoxifen Dong Quai Contains coumarin GI disturbances, photo Warfarin: Advise patients to use sun block constituents that sensitivity reactions May potentiate anti- when outside have vasodilatory coagulant effects properties. Binds Caution patients with estrogento estrogen re- sensitive conditions to avoid use ceptors and in- (e.g., breast, uterine, or ovarian duces transcrip- cancer; endometriosis; uterine tion in estrogen- fibroids) responsive cells. Vitamin E Inhibits low- GI disturbances, rash, Anticoagulants: Caution patients to avoid antidensity lipo- fatigue, creatinuria, May potentiate anti- oxidants after angioplasty, as protein (LDL) & possible thrombotic coagulant effects they may promote fibrosis at the platelet aggre- effects (is controversial) angioplasty site gation through Chemotherapeutics: unknown mech- May reduce effective- Caution against use by patients anisms ness of chemotherapy with retinitis pigmentosa as visual loss may worsen Statins: May reduce antilipid effects Caution against use by patients with vitamin K deficiency as it may exacerbate bleeding tendencies Nursing Implications Although herbal and dietary supplements are widely used for alleviating menopausal symptoms, data supporting their safety and efficacy are limited. Currently available evidence indicates that many herbal and dietary therapies used to manage menopausal symptoms may be ineffective or have safety concerns. The potential for drug interactions and implications for nursing practice are provided in Table 1. By asking about alternative therapy use and being knowledgeable about recent research findings and reliable resources, nurses can effectively educate menopausal women about safety and efficacy issues surrounding the use of herbal and dietary supplements (see the Lifelines Patient Page for additional resources about herbal and dietary supplements for hot flashes). October November 2003 AWHONN Lifelines 419

7 References Albertazzi, P., Pansini, F., Bonaccorsi, G., Zanotti, L., Forini, E., De Aloysio, D. (1998). The effect of dietary soy supplementation on hot flushes. Obstetrics and Gynecology, 91, Barton, D. L., Loprinzi, C. L., Quella, S. K., Sloan, J. A., Veeder, M. H., Egner, J. R., et al. (1998). Prospective evaluation of vitamin E for hot flashes in breast cancer survivors. Journal of Clinical Oncology, 16, Beuscher, N. (1995). Cimicifuga rasemosa L. black cohosh. Z Phytotherapie, 16, [Reprinted in English: Clay A. Reichert, translator. (1996). In Quarterly Review of Natural Medicine, spring, ] Blumenthal, M. (1998). The German Commission E monographs: Therapeutic guide to herbal medicines. Austin, TX: American Botanical Council. Brucker, M. B., and Youngkin, E. Q. (2002). What s a woman to do: Exploring HRT questions raised by the women s health initiative. AWHONN Lifelines, 6(5), Chlebowski, R. T., Hendrix, S. L., Langer, R. D., Stefanick, M. L., Gass, M., Lane, D., et al. (2003). Influence of estrogen plus progestin on breast cancer and mammography in healthy postmenopausal women: The Women s Health Initiative Randomized Trial. Journal of the American Medical Association, 289, Cockey, C. D. (2003). Is an ephedra ban coming: HHS, FDA warn, seek comment regarding supplement. AWHONN Lifelines, 7(2), Dormire, S. L. (2003). What we know about managing menopause hot flashes: Navigating without a compass. Journal of Obstetric, Gynecologic, and Neonatal Nursing, 32(4), Grady, D., Herrington, D., Bittner, V., Blumenthal, R., Davidson, M., Hlatky, M., et al. for the HERS Research Group. (2002). Cardiovascular disease outcomes during 6.8 years of hormone therapy: Heart and estrogen/progestin replacement study follow-up (HERS II). Journal of the American Medical Association, 288(1), Herrington, D. M., & Howard, T. D. (2003). From presumed benefit to potential harm hormone therapy and heart disease (Perspective). New England Journal of Medicine, 349(6), Hiruta, J. D., Swiersz, L. M., Zell, B., Small, R., & Ettinger, B. (1997). Does dong quai have estrogenic effects in postmenopausal women? A double blind, placebocontrolled trial. Fertility and Sterility, 68, Hulley, S., Furberg, C., Barrett-Connor, E., Cauley, J., Grady, D., Haskell, W., et al. for the HERS Research Group. (2002). Noncardiovascular disease outcomes during 6.8 years of hormone therapy: Heart and estrogen/ progestin replacement study follow-up (HERS II). Journal of the American Medical Association, 288(1), Jacobson, J. S., Troxel, A. B., Evans, J., Klaus, L., Vahdat, L., Kinne, D., et al. (2001). Randomized trial of black cohosh for the treatment of hot flashes among women with a history of breast cancer. Journal of Clinical Oncology, 19, Kelly, B. D. (2001). St. John s wort for depression: What s the evidence? Hospital Medicine, 62(5), Kronenberg, F., & Fugh-Berman, A. (2002). Complementary and alternative medicine for menopausal symptoms: A review of randomized, controlled trials. Annals of Internal Medicine, 137(10), Liske, E. (1998). Therapeutic efficacy and safety of Cimicifuga racemosa for gynecologic disorders. Advances in Natural Therapy, 15, National Institutes of Health, National Center for Complementary and Alternative Medicine (NCCAM), Office of Dietary Supplements. (2003). Questions and answers about black cohosh and symptoms of menopause. Retrieved May 28, 2003, from NIH Web site: Pepping, J. (1999). Black cohosh: Cimicifuga racemosa. America Journal of Health-System Pharmacy, 56, Rossouw, J. E., Anderson, G. L., Prentice, R. L., LaCroix, A. Z., Kooperberg, C., Stefanick, M. S., et al. Writing Group for the Women s Health Initiative Investigators. (2002). Risks and benefits of estrogen plus progestin in healthy postmenopausal women. Principal results from the women s health initiative randomized controlled trial. Journal of the American Medical Association, 288(3), Scambia, G., Mango, D., Signorile, P. G., Anselmi, A. R. A., Palena, C., Gallo, D., et al. (2000). Clinical effects of a standardized soy extract in postmenopausal women: A pilot study. Menopause, 7, Shaw, C. R. (1997). The perimenopausal hot flash: Epidemiology, physiology, and treatment. The Nurse Practitioner, 22(3), Sloan, J. A., Loprinzi, C. L., Novotny, P. J., Barton, D. L., Lavasseur, B. I., & Windschitl, H. (2001). Methodologic lessons learned from hot flash studies. Journal of Clinical Oncology, 19(23), Van Patten, C. L., Olivotto, I. A., Chambers, G. K., Gelmon, K. A., Hislop, T. G., Templeton, E., et al. (2002). Effects of soy phytoestrogens on hot flashes in postmenopausal women with breast cancer: A randomized, controlled clinical trial. Journal of Clinical Oncology, 20, AWHONN Lifelines Volume 7 Issue 5