Dr. Brown is an assistant professor of pharmacy practice at Palm Beach Atlantic University, Lloyd L. Gregory School of Pharmacy, West Palm Beach, Florida.
Though menopause is a normal part of the aging process for most women, this change can have physical and psychological implications. In fact, up to 85% of women experience menopausal symptoms, including hot flushes, night sweats, insomnia, and vaginal dryness that can lead to painful sexual intercourse.1 Additionally, concomitant depression and anxiety may stem from this biological process. Thus, it is not surprising that many women will seek medical advice for the alleviation of these symptoms as they can have a significant impact on their quality of life.
In addition to nonpharmacologic recommendations, such as smoking cessation, increased physical activity, and minimizing alcohol intake, hormone replacement therapy (HRT) is perhaps the most effective therapy for the relief of the aforementioned menopausal symptoms.1 In light of data that suggest a potential increased risk for cancer, cardiovascular disease, and venous thromboembolism (VTE), however, many women are hesitant to begin HRT.2-5
Many women prefer a more natural approach to treatment and are turning to the use of dietary supplements for the relief of menopausal symptoms. One small study showed that women who used dietary supplements as part of the management of menopause, either as monotherapy or in combination with HRT, reported overall control of their menopausal symptoms and an improved quality of life.6
Pharmacists are in the prime position to advise patients on the appropriate use of these supplements for symptom alleviation. Though many complementary alternative medicine options exist, some products that commonly are sought out by women to treat menopausal symptoms include black cohosh, soy, dong quai, ginseng, vitamin E, red clover, and kava. This article focuses on the use of black cohosh and soy.
Studies suggest that black cohosh appears to reduce menopausal symptoms modestly, especially hot flushes.7,8 One 3-month study found that 40 mg/day of black cohosh was similar in hot flush reduction, compared with transdermal estradiol 25 mcg applied weekly. Effects were seen by the first month and maintained throughout the remainder of the study.8
Additionally, the use of black cohosh in combination with St. John's wort has shown improvements in both hot flush complaints and depressive symptoms.9 Although most studies have only assessed the safety and efficacy of black cohosh for up to 6 months, 2 studies demonstrated the safe use of black cohosh supplements for up to 1 year.10,11
Black cohosh appears to be effective in the treatment of menopausal symptoms by acting like an estrogen receptor modulator, producing estrogenic effects on bone, but causing antiestrogenic effects on other tissues. One animal study suggests that black cohosh does not increase the risk for breast cancer; however, it increased the risk for metastatic cancer in those animals with existing cancer.12
Conflicting data exist on whether black cohosh is safe and effective for the alleviation of hot flushes in women who are breast cancer survivors.13-15 Though black cohosh does not appear to affect estrogen receptors, the use of the supplement has not been studied in long-term trials, and therefore, the use of black cohosh?containing products is not recommended in women with hormone-sensitive cancers, such as breast, uterine, and ovarian.
Common adverse effects reported with black cohosh are gastrointestinal (GI) upset, abdominal pain, breast tenderness, and vaginal spotting or bleeding. 16-18 A rare but serious potential adverse effect is hepatitis. Thus, routine assessment of liver function is advised.19 It is also important to note that black cohosh should not be confused with blue or white cohosh.
Research suggests that black cohosh modestly inhibits the cytochrome P450 isoenzyme 2D6.20 Drugs such as amitriptyline, haloperidol, paroxetine, and ondansetron, among others, are metabolized through this isoenzyme, and concentrations may be prolonged with concomitant administration of black cohosh. Caution is warranted with concomitant use of these agents.
Women electing to use black cohosh also should be counseled that immediate relief of symptoms should not be expected, and it can take up to 4 weeks to see effects.8
The effects of soy on relieving hot flushes have been investigated after recognizing that Asian women who typically have a diet high in soy reported lower rates of hot flushes, compared with American women. Soy contains isoflavones, a type of phytoestrogen that possesses weak estrogenic activity to relieve hot flushes.1 Clinical data show conflicting results on the efficacy of soy to minimize menopausal symptoms, however.11,21-24 One 6-month trial comparing 0.625 mg daily of conjugated equine estrogens with a standardized isoflavone-containing product demonstrated similar efficacy between the 2 products.25
The average dose of isoflavones studied has ranged from 40 to 80 mg daily. Though many foods such as soy milk, soy sauce, and soy nuts contain isoflavones, supplementation is typically required to achieve maximum benefits.1 This is because approximately 1 g of soy only contains between 1.2 and 1.7 mg of isoflavones, which is much less than the studied amounts of 40 to 80 mg daily.
The most common adverse effect is GI distress, including diarrhea, nausea, bloating, and constipation.26 Due to estrogenic effects, concern exists about soy's potential to increase the risk for breast and endometrial cancers. This concern is validated as findings from a 5-year study of isoflavones suggest a potential risk for endometrial cancer.27 Therefore, similar to black cohosh, the use of soy in patients with a history of hormone-sensitive cancers is not recommended.1
Patients may ask if the use of soy increases the risk for VTE, especially in light of the risk associated with estrogen therapy. Currently data do not suggest that soy has any effects on coagulation or fibrinolysis.28
Drug interactions are also an important consideration when counseling patients on these products. Normal gut flora is partially responsible for converting isoflavones to more biologically active components. Thus, antibiotics that wipe out gut flora reduce the efficacy of soy-containing products, decreasing the efficacy of soy during this time and following completion of the antibiotic until regeneration of gut flora occurs.29 Additionally, information from a case report of a patient receiving warfarin and consuming soy milk found the international normalized ratio was reduced.30 Thus, close monitoring of patients on warfarin using soy supplements is warranted, especially with initiation and titrations.
Dietary supplements commonly are sought out by patients for various reasons. As they are available over the counter, patients may believe the use of herbal products is undoubtedly safe. As a pharmacist, it is prudent to assess each patient's symptoms, ask about medical conditions and current medications, as well as consider a patient's allergy information, prior to making a recommendation.
Neither black cohosh nor soy should be recommended in women with a history of hormone-sensitive cancers. Additionally, both agents have potential drug?drug interactions that will likely merit close monitoring. Thus, basic knowledge about common herbals, such as black cohosh and soy, that are used for the management of menopausal symptoms is imperative to optimizing patient outcomes.
The Oncology Care Pharmacist in Health-System Pharmacy
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