The Effectiveness of Black Cohosh on Reducing the Occurrences and Severity of Menopausal Hot Flashes and Other Climacteric

Symptoms

Kirsten Matheson HSCI 4930 Medical Nutrition Therapy Literature Review December 2012

Abstract Objective: All women will experience menopause at some time in their lives. It may be the natural result of aging or could be brought on by breast or ovarian cancer. Regardless of when or why menopause starts, most women will experience uncomfortable to debilitating symptoms. The search for relief of these symptoms has led to the development of various therapies, one being black cohosh. The purpose of this literature review is to review the current literature on the effectiveness of black cohosh on reducing the occurrences and severity of menopausal hot flashes and other climacteric symptoms. Conclusion: Based on the review of this literature, the use of black cohosh for the treatment of climacteric symptoms caused by perimenopause and menopause is a viable treatment for the treatment of hot flashes. The clinical trial found no harmful effects when the safety, tolerance and toxicity of black cohosh were examined.

The Effectiveness of Black Cohosh on Reducing the Occurrences and Severity of Menopausal Hot Flashes and Other Climacteric Symptoms

Introduction

With our aging society, more and more women are experiencing perimenopause and menopause. Menopause is the time in a womans life when ovulation and menstruation cease.1 This usually occurs between the ages of 45 and 55 years old. Menopause officially starts 12 consecutive months after the occurrence of a womans last menstrual period. Prior to menopause, perimenopause occurs. The start of perimenopause is more variable than that of menopause, usually starting when a woman is in her forties but sometimes starting as early as the thirties.1 Perimenopause is marked by the start of irregular menstrual periods. These menstrual periods are longer, shorter, heavier or lighter, with the interval between being more or less than the average 28 days.1 The physiology behind menopause and perimenopause is the gradual reduction in the availability of ovarian primordial follicles. These follicles, located

in the cortex of the ovaries, are activated on a monthly basis during the ovarian cycle. The number of follicles available remains fairly constant from puberty to perimenopause at which time there is a dramatic monthly decrease in the number of the follicles. The low number of primordial follicles causes a decline in estrogen levels. If the estrogen levels are too low, ovulation will not occur.1 The number of follicles continues to drop until there are no primordial follicles left. Circulating concentrations of both estrogen and progesterone also decline dramatically. Physical changes include the reduction in the size of the breast and uterus and thinning of the urethral and vaginal lining. 1 Neurological effects include the traditional hot flashes, anxiety and depression. Hot flashes are caused by elevated body temperature associated with surges in hormone production. The causes of these central nervous system problems are not well understood. These symptoms can occur during perimenopause, during menopause and after menopause. These symptoms are referred to as menopausal or climacteric symptoms. Climacteric is defined as a period of decreased reproductive capacity in men and women, culminating, in women, in the menopause. 2 These menopausal symptoms occur in varying degrees of severity and duration. Some women experience very mild symptoms for a short time while others experience seriously debilitating symptoms for extended periods. For women experiencing severe symptoms, hormonal replacement therapy (HRT) has been the standard prescribed treatment. HRT involves replacing the missing estrogen and progestin orally in pill form, via injections or with a patch containing the replacement hormones.1 This therapy has

been found to be very effective. Replacing the missing hormones prevents the symptoms of menopause from occurring. Health care providers often prescribe HRT

before a woman even starts having menopausal symptoms. Perceptions dramatically changed regarding HRT in 2002. The Women's Health Initiative of the National Institutes of Health announced that reputable scientific studies had found links between long term use (5 years or more) of HRT with increased risks of heart disease, breast cancer, Alzheimer disease, blood clots and stroke.1 Thousands of women immediately stopped HRT due to these warnings. While there are some health benefits to HRT, the recommendation currently, is to use HRT only when absolutely necessary and at the lowest dose possible for the shortest time possible. Because of the risks of HRT, women turned to alternative and nontraditional therapies to help alleviate their climacteric symptoms. Some complementary and alternative treatments that are being used and studied include phyoestrogens, vitamin E, yoga, acupuncture, and black cohosh.3 Black cohosh, known as both Actaea racemosa and Cimicifuga racemosa, is a member of the buttercup family. It is a perennial plant that is native to North America.4 It was used by Native Americans as a treatment for many conditions primarily gynecologic issues. Its use has continued in the United States to treat a wide variety of ailments. It is currently used extensively in Europe for alleviation of menopausal symptoms, especially hot flashes. The mechanisms of the actions of black cohosh are not currently understood. It appears to have an estrogenic effect but studies have yielded contradictory results. It may be that black cohosh acts through systems involving neurotransmitters and inflammatory pathways rather than estrogenic pathways.5 Further research must be performed to determine both the causes of hot flashes and the mechanisms of black cohosh in order to provide effective therapies.

Due to a surge in popularity of black cohosh usage in the treatment of hot flashes as well as other menopausal symptoms, questions of its effectiveness and safety have resulted in many studies being performed. This paper will review the current literature on the effectiveness and safety of black cohosh and evaluate the findings.

Review of Literature

In 2002, a study to evaluate the effectiveness of black cohosh and its estrogenic effect was performed by Liske et al.6 This study was a controlled, randomized, doubleblind parallel group study. The study tested the safety and effectiveness of the standard prescribed dosage of 39 mg per day as well as a much higher dose of 127 mg per day. 123 perimenopausal and menopausal women participated in the initial 12 week study. The study was extended for an additional 12 weeks with 116 women continuing their participation. The participants were divided into two groups, one received the standard dose of 39 mg of black cohosh, the other group received 127 mg of black cohosh. The black cohosh formula was a commercially prepared, over the counter product called Remifemin6. The study used the Kupperman Menopause Index to determine efficacy as well as the Self-Rating Depression Scale (SDS). These evaluation tools measure severity of climacteric symptoms. The participants completed these surveys at baseline and then every two weeks during the main study period and twice more for the extended study period. Physiological parameters were evaluated by obtaining vaginal cell and serum samples at weeks 0, 4, 12 and 24. The vaginal cell samples measured cell proliferation and the serum samples were used to evaluate hormones levels. The results of the study showed that both dosages of black cohosh substantially reduced the
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severity of climacteric symptoms with no significant difference between dosage amounts. In sub type analysis, perimenopause versus menopause, there was a small increase in effectiveness in the high dosage for the perimenopause group. Examination of the physiological samples showed normal proliferation in vaginal epithelium and no alterations or increases in hormone levels. These physiological results indicate the lack of estrogenic effect. Overall, the finding of this study showed positive results using black cohosh as a viable and safe treatment for climacteric symptoms for at least 24 weeks as qualified by the authors. This study was weakened by the lack of a placebo group, its short time frame and the ties that one of the main authors had to the company that manufactured the black cohosh preparation used in the study. A study of black cohosh effectiveness performed in 2002 by Pockaj et al7 looked specifically at women who were breast cancer survivors, were at high risk for breast cancer or were reluctant to take HRT because of the potential risk of breast cancer. Links have been found between estrogen and the development of breast cancer so it is recommended that this population avoid medicines and foods containing estrogen such as soy products and HRT7. Because of the estrogen concerns, the study also looked at the potential production of estrogen from black cohosh. Due in part to its specificity, this study was much smaller than the previous study, consisting of only 21 women. The study period was short; only covering 5 weeks with the first week of this period being a baseline week. As in the previous study, participants were given black cohosh in the commercial, over the counter preparation, Remifemin. Patients receiving tamoxifen or raloxifene for breast cancer treatment had to have started these at least 1 month before the study and continued this therapy during the entire trial. Tamoxifen is currently

used for the treatment of both early and advanced estrogen receptor positive (ER+) breast cancer. Raloxifene is an oral selective estrogen receptor modulator (SERM) that has estrogenic actions on bone and anti-estrogenic actions on the uterus and breast. It is used in the prevention of osteoporosis in postmenopausal women. The participants were asked to self-report on their symptoms during the course of the study. An estrogen-dependant strain of S. cerevisise was cultured in yeast but was unable to grow with black cohosh. Based on this assay, it was concluded that black cohosh did not produce estrogen. The results of the trial showed a decrease in both the frequency and severity of menopausal symptoms in the trial subjects. Accurately labeled as a pilot, this study suggested their positive results warranted developing randomized trials to further evaluate both the effectiveness and safety of black cohosh as a viable treatment for women with breast cancer concerns as well as all women experiencing menopausal symptoms. The small sample size used by this study could contribute to a nonparametric test and samples size bias. Rostock et al8 performed a more recent study on the effects of black cohosh on breast cancer survivors. The 50 women included in this study all had undergone breast cancer surgery, most had received radiation therapy and half had received chemotherapy. All of the women were receiving tamoxifen. The authors reviewed trials that studied the effectiveness and safety of black cohosh of breast cancer survivors using tamoxifen. Because all of the existing studies were inconclusive, the authors hoped to provide conclusive data on the use of black cohosh with this specific population. During the study, the participants self-reported on their symptoms using the Menopause Rating Scale (MRS) questionnaire. The MRS was used to rate the severity

of menopausal symptoms and was completed at baseline, 1, 3 and 6 months. Tumor reports were obtained for comparison to determine tumor development or reoccurrence during the test period. The 50 participants were given the standard daily dosage of 40 mg per day using the commercial black cohosh preparation, Remifemin. The participants were able to increase or decrease their dosage after the first four weeks. They were also able to use a combination of black cohosh and St. Johns wort. The authors reasoning for this was to allow the participants to adjust their dosages based on their self-assessment. While changing the treatment may create better patient outcomes, it is difficult to quantify and analyze results and weakens the study. The participants did reported reduction of severity in symptoms regardless of changes in dosage. Tumor growth was reevaluated at the conclusion of the study and reported as negative. The study concluded that while the effectiveness of black cohosh should be tested further, it appeared to be a possible therapeutic option for those needing to avoid hormonally based treatment for menopausal symptoms. This study was funded by the manufacturers of Remifemin which could have introduced a bias on the findings. Briese et al9 conducted a study to explore the effectiveness of black cohosh and a black cohosh and St Johns wort mixture on relieving menopausal symptoms in a nonspecific, general population of affected women. St Johns wort is an herb native to Europe, now found globally. The herb has been used for years for depression and depressive conditions such as anxiety, tiredness, loss of appetite and trouble sleeping. There is strong scientific evidence demonstrating the effectiveness of St. Johns wort on mild to moderate depression. The commercial preparation of Remifemin comes in two versions; one with black cohosh extracts, and Remifemin Plus, with black cohosh and

St Johns wort extracts. This prospective, non-randomized, open-label, observational study evaluated the effectiveness of both formulas as well as determining if Remifemin Plus was superior to the basic Remifemin formula for treatment of menopausal symptoms that included depression. The study also gathered data on usage patterns such as how the supplements were being prescribed, to whom and when. Tolerability data was collected and evaluated as well. The Menopause Rating Scale (MRS) was used to evaluate effectiveness of the treatments. The study started with 6,141 participants and concluded with 5,373 completing at least the initial six months of the study. Further data was collected for another six months but the number of participant remaining after twelve months was not noted in the article. This study differed in several aspects from the other studies reviewed. It was an observational study in which the authors did not select participants specifically for the study. The participants were random patients starting treatment for menopausal symptoms. The attending physicians decided which patients were treated with the black cohosh alone or the preparation of black cohosh with St. Johns wort. The patients were asked to complete the MRS before starting treatment, at three months, at six months and at twelve months. Data collected from the physicians indicated that the patient was more likely to receive the Remifemin Plus preparation with St. Johns wort when there was high severity of depressive moods, nervousness and irritability or overall higher severity of all symptoms. Both groups responded very well to treatment with an overall drop in symptom severity for both. The combination therapy group saw a greater decrease in depressive moods, nervousness and irritability. Interestingly, the severity of symptoms for both groups reached a plateau at six months and remained steady until the studys

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conclusion at twelve months. Tolerability was very high with only a few participants reporting adverse effects. A weakness of this study was that it was funded by the manufacturers of Remifemin which could have introduced a bias on the findings. The strengths of the study were the large sample size which helps alleviate bias and the extended length of the study. The study carried out by Osmers et al10 was a randomized, double-blind, clinical trial with a placebo control. A total of 304 participants were randomly selected to receive a daily dose of 40 mg of black cohosh extract in the form of Remifemin or a matching placebo daily for twelve weeks.10 Efficacy was measured using the Menopause Rating Scale (MRS), looking for changes in symptom severity from the baseline measurements to the studys completion. Safety and tolerability of the study medication were measured by adverse events, evaluation of liver enzymes, vital signs, body weight, and physical examination. Participant inclusion criteria were well detailed and strictly enforced. Of the initial 304 participants, 268 patients completed the study without violations. The participants were evenly divided into two groups based on demographics and baseline data including severity and frequency of symptoms. Baseline data for laboratory measures showed no clinically relevant differences between the treatment groups. At the end of the study period, the data were systematically and thoroughly analyzed. The results revealed that there were statically significant differences in efficacy favoring the black cohosh group. The laboratory results showed that the use of black cohosh did not elevate liver enzyme activity in peripheral blood and the rate of changes in enzyme levels was equal in both the black cohosh group and the placebo group. The studys black cohosh efficacy was found to

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be similar to that found in comparable studies of HRT efficacy. Black cohosh appeared to be more beneficial to women in the early climacteric phase of menopause and most effective on hot flashes over other symptoms. This study compared the efficacy of their study to the results of other studies on the efficacy of HRT but did not test the two treatments simultaneously. The authors of this study did suggested further studies be conducted specifically comparing black cohosh to HRT in one study.

The study done by Ubelhack et al11 expanded on the Briese et al study 9 by developing a 16 weeks, doubleblind, randomized, placebo controlled study to test the effectiveness of Remifemin Plus which contains black cohosh and St. Johns wort. The objective of this study was to evaluate the efficacy of Remifemin Plus for climacteric and associated psychological complaints. Based on a review of current trials, the study expected the Remifemin Plus group to exhibit better results than the placebo group. The Menopause Rating Scale (MRS) was used to evaluate climacteric symptoms while psychological component was measured using the Hamilton Depression Rating Scale. Potential participants needed to pass strict exclusion criteria before being accepted into the study. The exclusion criteria ruled out interfering factors that could be caused by illness, disease, other climacteric symptom relief treatments, pharmaceutical therapies or any abnormalities. The study involved 301 participants. 151 of these subjects received the Remifemin Plus treatment and 150 received the placebo. No significant differences were observed between the two groups in relation to age, body height, body weight and body mass index. The participants were interviewed and measurement surveys were completed on the baseline visit, on the second visit at three week and at

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the final visit at 16 weeks. Analysis of the data at the conclusion of the study showed positive outcomes for the Remifemin Plus treatment group. The primary outcome was a decrease in both the MRS scores and the Hamilton Depression Rating Scale scores. The MRS scores for the treatment group had decreased by 50% while the placebo groups scores decreased by 19.6%11. The mean Hamilton Depression Rating Scale total score of 18.9 points was observed in both groups at the study start. This score decreased by 7.9 points for the treatment group while only decreasing 2.4 points for the placebo group. The study found that the efficacy of the medication was judged as being moderate or very good for 78.8% of the treatment group but only for 14.9% of the placebo group.11 Similarly, only 7.9% of the participants in the treatment group judged their health condition unchanged or worse.11 Unchanged health conditions were reported for 51.7% of participants in the placebo group.11 The benefit-to-risk ratio of Remifemin Plus was proved to be very good and the therapy itself was effective for the treatment of climacteric complaints with a pronounced psychological component. This was a well designed double-blind study that provided a placebo group for comparison. Wuttke et al12 developed just such a study to test the effectiveness of black cohosh compared to HRT for the relief of climacteric symptoms. This was a double-blind, randomized, placebo- and conjugated estrogens-controlled study that followed 95 women for twelve weeks. The participants were selected based on strict inclusion criteria attempting to eliminate conditions that would affect the efficacy of the treatments. The participants were randomly placed into one of three groups the black cohosh group, the HRT group or the placebo group. Age, height, weight, and intensity of climacteric symptoms were recorded at baseline and were found to be comparable in all

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treatment groups. The study treatments were prepared to appear completely identical to protect the objectivity of the participant reactions. The measurement tool used to determine efficacy was the Menopause Rating Scale (MRS). Baseline data was obtained for two prior to the start of the study with participants documenting daily the number of sweating episodes and sleep disturbances they experienced. Participants continued this documentation throughout the treatment period.12 Blood samples were collected at the start of the run-in period, at baseline and after 4, 8, and 12 weeks to determine hormone levels. Participants were questioned at each visit about the occurrence of adverse effects and any changes that had occurred that could affect the test results. At the conclusion of the study, the MRS scores demonstrated a significant decrease in the severity of the climacteric symptoms for both the black cohosh and the HRT groups with the black cohosh group reporting significantly better improvement at twelve weeks. However, the placebo group showed very little improvement after the twelve weeks.12 The review of the daily diary entries showed dramatic decreases in the frequency of symptoms in the black cohosh group over both the HRT group and the placebo group.12 This study included 3 groups which provided good comparison data. The authors conclude that the treatment of black cohosh can be beneficial without potentially dangerous side effects.12 Newton et al13 designed a 1-year randomized, double-blind, placebocontrolled trial called Herbal Alternatives for Menopause Trial (HALT). The purpose of this trial was to test the efficacy of three herbal regimens and hormone therapy for relief of vasomotor symptoms compared with a placebo. The five treatments were 1) black cohosh at 160 mg per day, 2) multibotanical with 200 mg black cohosh and 9 other

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ingredients; 3) multibotanical plus dietary soy counseling; 4) estrogen, 0.625 mg daily; or 5) placebo. Eligibility criteria were age 45 to 55 years, late menopausal transition or postmenopausal. Few studies have targeted this specific population to evaluate the effectiveness of black cohosh on climacteric symptoms. The 351 women participating in the study were evenly divided into 5 treatment groups. Each group was evaluated at baseline, at 3 months, 6 months and at the 12 month study conclusion. The primary outcomes measured were the frequency and intensity of daytime hot flashes and nighttime sweats, and the mean Wiklund Vasomotor Symptom Subscale score. The Wiklund Vasomotor Symptom tool rates the severity of 13 menopausal symptoms (sweats, hot flashes, sleep disturbance, fatigue, vaginal dryness, depression, headache, irritability, muscle/joint pain, breast tenderness, nervousness, palpitations, and dizziness/fainting on a scale of 0 (none) to 10 (severe)13. The results of the study showed a decrease in all groups for the vasomotor symptoms at 3 month, using both measurements. There were no statistically significant differences in the herbal treatment group and the placebo group for changes in vasomotor symptoms per day or in vasomotor symptom intensity or in the mean Wiklund Vasomotor Symptom Scale at any time throughout the study. There were significantly significant changes in vasomotor symptoms per day and in vasomotor symptom intensity, and the mean Wiklund Vasomotor Symptom Scale between the placebo and HRT group throughout the study.13 The authors concluded that black cohosh has no value as a treatment for climactic symptoms. The authors noted that there were some differences in their study compared to other studies that found black cohosh effective. Some of the differences noted were difference in formulation; isopropyl alcohol extract versus ethanol extracts

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and dosage and overall duration of the study. This study targeted only late menopausal or postmenopausal women, excluding perimenopausal and early menopausal women. The exclusion of this population could have affected the results. Amsterdam et al14 reviewed numerous surveys that reported menopausal women were experiencing more physiological symptoms than vasomotor symptoms. The physiological symptoms included irritability, anxious mood, depressed mood, and concentration problems were being reported that hot flashes and night sweats. Based on these surveys, Amsterdam et al14 conducted a randomized, double-blind, placebocontrolled, parallel group trial evaluating the efficacy and tolerability of black cohosh for the treatment of anxiety disorder due to menopause. Study participants were randomized to therapy with either pharmaceutical-grade black cohosh or placebo for up to 12 weeks. Hamilton Anxiety Rating Scale (HAM-A) scores were used as the primary measure. Changes in the scores would indicate effectiveness. Secondary outcomes included a change in scores on the Beck Anxiety Inventory, Green Climacteric Scale (GCS), and Psychological General Well-Being Index (PGWBI). The study intended to have a sample size of 50 participants but was only able to include 20 participants. The participants were given increased doses of black cohosh at weeks 2, 4, 8, and 12 with doses of 64 mg, 119.3 mg, 128 mg, and 128 mg, respectively. At the end of the study, the participants scores were analyzed and no changes were noted. The authors concluded that black cohosh was not an effective treatment option for anxiety in menopausal women. The authors did note that their sample size was extremely small which may have skewed the results. They also noted that the particular preparation and dosage used could affect the anxiolytic activity of black cohosh.

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Summary of Current Research

The reviewed studies examined the effectiveness and safety of black cohosh as a treatment for the relief of menopausal symptoms. These studies were all research studies with the exception of the Briese et al study9 which was an observational study. The Liske et al study 6 was a randomized, double blind, controlled study but it lacked a placebo group. The study determined that while increasing the dosage was not harmful, it had no effect on results. The results obtained using the recommended dose were positive in favor of black cohosh. The lack of a placebo weaken the study and made a good comparison difficult. The study done by Osmer et al10 was a randomized, double-blind, clinical trial with a placebo control. The participants in the black cohosh group showed a significant reduction of symptoms over the placebo group. Another placebo controlled study12 was conducted with the addition of a HRT group. The placebo group showed very little improvement. The black cohosh group and the HRT group had a significant decrease in severity of symptoms with the black cohosh showing better improvement at 12 weeks. The two most variable parameters in these studies were the number of participants and the duration of the studies. The number of participants ranged from 20 and 21 participants7,14, and to over 5000 in the observational study9. These extremes in participation can affect the statistical analysis of the results. The duration of the studies also varied greatly. The studies were as short as five weeks7 and as long as one year6, 9, 13. The observational study9 noticed a plateau in severity of symptoms at six months. The study does not explain why this plateau occurred or investigate its
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significance. The duration of the treatment could have a significant effect on overall therapy. Other inconsistent variables among the studies were the ages of the women and the menopausal phase. The Pockej et al study included any women older than 18 years old experiencing hot flashes. 7 In the Rostock et al study, the participants were aged 44-72 years, with 74% being postmenopausal.8 Briese et al included anyone with any menopausal symptoms regardless of age or menopause phase. 9 Liske et al, Amsterdam et al and Wuttke et al had comparable perimenopausal and postmenopausal women aged over 40 to 76 years old.6,12, 14 The women in the Ubelhack11 study were between 45 and 60 years of age experiencing climacteric complaints with a pronounced psychological component. Omers et al10 recruited 45- 61 year old postmenopausal women. Newton et al studied women 45 to 55 year old; 52% of the women were in menopausal transition and 48% were postmenopausal. The ages of the participant have ranged from 18 years to at least 76 years old and the women were in various stages of menopause. These variations in the study subjects could have effected the study outcome in different ways, either positive or negatively. The study done by Pockej et al7 investigated hot flash reduction in women with breast cancer concerns. The study did find a reduction in hot flash occurrence. Ubelhack et al11 performed a similar study with breast cancer survivors. Neither study used a placebo group and both showed positive results. Interestingly, the breast cancer survivors were able to increase or decrease their dosage after four weeks. This was to allow for better efficacy but it created on uncontrolled variable that most likely influenced the results. Unlike the Liske et al6 study which measured estrogenic activity by

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obtaining vaginal cell samples, Pockej et al7 study used a growth-based assay that was observed for four days. This significant difference in methods to determine if black cohosh elicits estrogenic activity could produce very different results. Some of the studies6, 7, 8, 9, 11 used the same preparation of black cohosh, the German commercially available, Remifemin, which produced positive results. The study by Wuttke12 also used a German commercially available preparation with positive results. The studies6,8, 9,11 that used the commercially prepared black cohosh were funded by the manufacturers which bring to question their objectiveness and raises conflict of interest issues. The studies13, 14 with negative results for black cohosh effectiveness used different preparations which could have affected their results. Amsterdam et al14 attempted to study the effect of black cohosh on menopausal anxiety. The authors hypothesized that the black cohosh would be more effective than the placebo in the reduction of anxiety. Unlike the studies done by Briese et al 9 and Ubelhack et al11, the authors did not use St. Johns wort in addition to the black cohosh. Amsterdam et al14 did not explain the basis for this. Black cohosh is mainly used for the treatment of hot flashes. It is not generally used solely for the treatment of anxiety. It is not surprising that the results did not support the authors hypothesis. Ubelhack et al11 did use the combination black cohosh and St. johns wort and obtained positive results for both anxiety and hot flashes. The observational study 9 also used a combination therapy and reached the same conclusion as Ubelhack et al11 which showed positive results.

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Conclusion All women will experience menopause at some time in their lives. It may be the natural result of aging or could be brought on by breast or ovarian cancer. Regardless of when or why menopause starts, most women will experience uncomfortable to debilitating symptoms. The search for relief of these symptoms has lead to the development of various therapies, one being black cohosh. A search of the current literature examined the studies performed on the effectiveness of black cohosh. The studies focused on two primary outcomes. The outcomes evaluated are the effectiveness of black cohosh to treat the symptoms of menopause and the safety of using black cohosh. Based on the review of this literature, the use of black cohosh for the treatment of climacteric symptoms caused by perimenopause and menopause is a viable treatment. The results obtained may depend on the phase of menopause that is being treated. The majority of the research reviewed supports this finding. While the studies varied in their conclusion on the effectiveness, all of the studies that investigated the safety, tolerance and toxicity of black cohosh were unable to find harmful effects. The studies that looked at the estrogenic effects of black cohosh were unable to find evidence that black cohosh is estrogenic. The lack of estrogenic effect suggests that women with breast cancer concerns could use black cohosh to treat the climactic symptom of menopause. Black cohosh has been used for years as an alternative medicine. It has just recently entered the mainstream as a viable menopausal therapy. Due to its relatively new status there has not been the opportunity to study black cohoshs long term effects on the body. The harmful effects of HRT were not discovered until it had been in use for

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years and longitudinal studies were conducted. Similarly, alternative therapies such as black cohosh could potentially have long term harmful effects that have not yet been discovered. Longitudinal studies will need to be performed to determine the safety of its long term use. Studies differentiating the phases of menopause and severity, frequency and length of symptoms should designed as vast differences in could greatly affect the dosage amount and durations of supplements. The current studies do not differentiate clearly between the different phases and the severity of symptoms. Closely examining severe perimenopausel symptom compared to severe postmenopausal symptoms may yield vastly different result. These differences could lead to different treatment dosage and durations. Drug and food interactions should be studied while using black cohosh. There could be potential negative interaction with the latest anti-cancer drugs. Breast, uterine and cervical cancers can bring on climacteric symptoms. Studies should be done to insure that the relief brought by black cohosh interferes with the drugs fighting the cancers. The food consumed while taking black cohosh could interfere with its absorption or black cohosh could interfere with the absorption of nutrients. Further research into these topics may provide improved alternatives to current treatment of menopausal symptoms. Additional studies may lead to an understanding of the mechanics of black cohosh and why it has an effect on menopausal symptoms. This research could in turn lead to a better understand of menopause itself. Such a breakthrough could provide a better quality of life for women dealing with menopause.

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References

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9. Briese V, Stammwitz U, Friede M, Henneicke-von Zepelin H. Black cohosh with or without St. John's wort for symptom-specific climacteric treatmentResults of a large-scale, controlled, observational study. Maturitas [serial online]. August 20, 2007;57(4):405-414. 10. Osmers R, Friede M, Liske E, Schnitker J, Freudenstein J, Henneicke-von Zepelin H. Efficacy and Safety of Isopropanolic Black Cohosh Extract for Climacteric Symptoms. Obstetrics & Gynecology [serial online]. May 2005;105(5):1074-1083. 11. Uebelhack R, Blohmer J, Graubaum H, Busch R, Gruenwald J, Wernecke K. Black Cohosh and St. John's Wort for Climacteric Complaints. Obstetrics & Gynecology [serial online]. February 2006;107(2):247-255. 12. Wuttke W, Rau K, Gorkow C. Efficacy and tolerability of the Black cohosh (Actaea racemosa) ethanolic extract BNO 1055 on climacteric complaints: A double-blind, placebo- and conjugated estrogens-controlled study. Maturitas [serial online]. November 21, 2006;55:S83-S91. 13. Newton K, Reed S, LaCroix A, Grothaus L, Ehrlich K, Guiltinan J. Treatment of Vasomotor Symptoms of Menopause with Black Cohosh, Multibotanicals, Soy, Hormone Therapy, or Placebo. Annals Of Internal Medicine [serial online]. December 19, 2006;145(12):869-W244. 14. Amsterdam J, Yao Y, Mao J, Soeller I, Rockwell K, Shults J. Randomized, DoubleBlind, Placebo-Controlled Trial of Cimicifuga racemosa (Black Cohosh) in Women With Anxiety Disorder Due to Menopause. Journal of Clinical Psychopharmacology. , October 2009;29(5):478-483.

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