Broadening our perspectives on complementary and alternative medicine for menopause: A narrative review

Maturitas 99 (2017) 79–85

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Maturitas journal homepage: www.elsevier.com/locate/maturitas

Review article

Broadening our perspectives on complementary and alternative medicine for menopause: A narrative review Dunia Tonob a , Melissa K. Melby a,b,∗ a b

Department of Anthropology, University of Delaware, USA College of Health Sciences, University of Delaware, USA

a r t i c l e

i n f o

Article history: Received 19 January 2017 Accepted 26 January 2017 Keywords: Menopause Complementary and alternative medicine (CAM) Natural products Mind-body practices Traditional Chinese medicine (TCM) Japanese Kampo medicine

a b s t r a c t Complementary and alternative medicine (CAM) is widely used for menopause, although not all women disclose use to their healthcare providers. This narrative review aims to expand providers’ understanding of cross-cultural approaches to treating and managing menopause by providing an overarching framework and perspective on CAM treatments. Increased provider understanding and awareness may improve not only provider-patient communication but also effectiveness of treatments. The distinction between illness (what patients suffer) and disease (what physicians treat) highlights the gap between what patients seek and doctors provide, and may help clarify why many women seek CAM at menopause. For example, CAM is often sought by women for whom biomedicine has been unsuccessful or inaccessible. We review the relevance to menopause of three CAM categories: natural products, mind–body practices including meditation, and other complementary health approaches including traditional Chinese medicine (TCM) and Japanese Kampo. Assessing the effectiveness of CAM is challenging because of the individualized nature of illness patterns and associated treatments, which complicate the design of randomized controlled trials. Because many women seek CAM due to inefficacy of biomedical treatments, or cultural or economic marginalization, biomedical practitioners who make an effort to learn about CAM and ask patients about their CAM use or interest may dramatically improve the patient-provider relationship and rapport, as well as harnessing the ‘meaning response’ (Moerman, 2002) imbued in the clinical encounter. By working with women to integrate their CAM-related health-seeking behaviors and treatments, providers may also boost the efficacy of their own biomedical treatments. © 2017 Elsevier B.V. All rights reserved.

Contents 1. 2. 3.

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 80 Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 80 Evaluating CAM . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 80 3.1. RCT and western biomedical perspectives on CAM . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 80 3.2. Holistic perspective on CAM . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81 3.3. Developmental factors over the lifecourse . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81 3.4. Placebo effect versus meaning response . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82 4. Case studies of CAM . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82 4.1. Natural products . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82 4.2. Mind-body practices . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82 4.3. Traditional Chinese medicine (TCM) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82 4.4. Japanese Kampo . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83 5. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83 Contributors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .83

∗ Corresponding author at: Department of Anthropology, University of Delaware, 46 W. Delaware Ave., Newark, DE 19716, USA. E-mail address: [email protected] (M.K. Melby). http://dx.doi.org/10.1016/j.maturitas.2017.01.013 0378-5122/© 2017 Elsevier B.V. All rights reserved.

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Conflict of interest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83 Funding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83 Provenance and peer review . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83 Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83

1. Introduction The treatments sought by menopausal women are as diverse as the symptoms themselves and the methods used to study them [1–5]. While medicalized views of menopause and biomedical treatments such as hormone replacement therapy (HRT) have reached the far corners of the globe, traditional treatments have also spread globally, increasing the options available to menopausal women and their providers. Anthropological research suggests that biocultural factors (ranging from the physical environment in the form of diet and the microbiome, to the social environment in the form of social support, attitudes toward aging and medicalization) acting over the lifecourse may significantly influence women’s experience at and perception of menopause. These factors may also influence whether (and which) symptoms are bothersome, and what kinds of treatments are used and effective [6]. Many women seek complementary and alternative medicine (CAM) at menopause, as biomedicine is often perceived to be more aggressive [7]. The definition of CAM depends on who is using it and where. “Depending on one’s perspective, CAM is a category of exclusion, preventive and therapeutic modalities that fall outside the conventional [bio]medical practice, or a category of inclusion, a residuum of everything else, ranging widely from prayer to acupuncture to Ayurvedic plant medicines” (p. 204) [8]. Interest in CAM for menopause increased following results from the Heart and Estrogen/Progestin Replacement Study II and the Women’s Health Initiative [9] that suggested that HRT might increase risks of several chronic diseases such as coronary artery disease, stroke, thromboembolic events, and breast cancer [10–12]. To avoid potentially negative side effects of HRT [13], and because they perceive that CAM and conventional medicine combined (i.e., integrative medicine) is more effective [14], many women have turned to CAM for treatment of menopausal symptoms [15]. However, they do not always involve their physicians in the process [16], perhaps due to stereotypes on both sides. Women may assume that biomedical practitioners lack knowledge about CAM and associate negative stigma with CAM use [16]. Practitioners may hold negative stereotypes about CAM users, including that they are naïve or superstitious, although studies suggest these stereotypes are not entirely accurate [17,18]. One US study found that CAM users were generally better-educated and reported overall poorer health than those who used Western biomedicine exclusively [19], suggesting that subpopulations for whom biomedicine has not worked well are motivated to seek alternatives. CAM use in the United States has risen in recent years [20]. One in three Americans use some form of CAM and make more visits to CAM providers than to primary care physicians [21]. Thus, it is critical that practitioners understand more about CAM. The US National Center for Complementary and Integrative Health (NCCIH) divides CAM into three categories: natural products, mind–body practices including meditation, and other complementary health approaches including traditional Chinese medicine (TCM) and Japanese Kampo [22]. This review aims to provide an overview of CAM and a context for understanding CAM use by women, highlighting examples from each of the three NCCIH CAM categories. Readers who desire evidence from randomized controlled trials (RCTs) are referred to the many systematic reviews

and meta-analyses on CAM for treatment of menopause [15,23–29]. Many reviews have found inconclusive results, due in part to low quality studies of CAM. Space does not permit an exhaustive treatment of individual therapies. Rather, this narrative review aims to fill a gap in the literature, taking a step back from attempts to study CAM by biomedical standards of RCTs, by providing an overarching framework and perspective on CAM and integrative therapies for treatment of menopause. The goal of this narrative review is to expand providers’ understanding of cross-cultural approaches to menopause, thereby enabling them to open channels of communication with their patients, possibly add to their own bags of tools and treatments, and work more effectively with their patients to develop appropriate treatment options. As women around the world increasingly choose to explore CAM, it is important for their providers to have a ‘big picture’ understanding of how CAM may work so that they can harness its power in treating their patients. 2. Methods We searched PubMed and AnthroSource for articles related to CAM and menopause. Key words included: menopause AND complementary and alternative medicine or CAM; or herbal remedies; dietary phytoestrogens; supplements; moxibustion; acupuncture; aromatherapy; movement or meditation; lifestyle; traditional Chinese medicine (TCM); Chinese herbal medicine (CHM); or Kampo. Because we aimed to update the literature following the 2010 review of CAM and menopause [13], only English-language articles published between 2009 and 2016 were included. Additional references were identified from reference lists in the resulting publications, review articles, medical anthropology books on complementary and alternative medicine, and recommendations by colleagues working with CAM. Because this is a narrative review, rather than systematically summarizing results, we provide a broader framework for understanding and contextualizing the results of CAM studied by RCTs, and review literature on broader implications of CAM use and approaches. We highlight examples of three types of CAM to increase readers’ familiarity with different categories of CAM, and draw on medical anthropology literature to provide a more holistic perspective on CAM approaches so that biomedical practitioners can integrate an understanding of CAM into their provider-patient relationship. 3. Evaluating CAM 3.1. RCT and western biomedical perspectives on CAM The gold standard for evidence-based medicine (EBM) is the RCT. In biomedicine, blood tests and biomarkers (e.g. high FSH and low E2) may indicate a specific therapeutic course of action (e.g. HRT); however, in many CAM traditions, practice is empirical and individually-tailored to each patient’s symptoms and mind-body characteristics, as well as larger environmental contexts. Thus, different CAM treatments may be prescribed for biomedically-similar symptoms or conditions. However western biomedicine tends to privilege models of single causes and cures, an idea of the universal body or patient, and standardization and risk management that

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Integrative Medicine Harnesses Meaning Response

Complementary & Alternative Medicine

Biomedicine treats

treats

Disease

Mind-Body Therapies

Illness

Herbal Medicines: most easily understood & tested by biomedicine

TCM & Kampo

Physical & Psychosocial Environment OR Biocultural Environment

Fig. 1. Schematic of levels of action of three types of CAM: 1. herbal medicines, 2. mind-body therapies; and 3. TCM and Kampo. While biomedicine treats disease, and CAM treats illness, integrative medicine holds the promise of treating both by harnessing the meaning response.

render it difficult for many biomedical practitioners to accept that different CAM treatments may be equally effective [7]. The distinction between illness (what patients suffer) and disease (what physicians treat) highlights the gap between what patients seek and doctors provide [30], and may help explain why many women seek CAM at menopause (Fig. 1). Although changing hormones are a natural and inevitable part of aging, decreased estradiol and increased FSH are often considered to mark a potential disease state (menopausal syndrome) that requires treatment. Cross-cultural studies of the subjective experience of illness (impaired functioning) associated with menopause have challenged the normative biomedical model [6,13]. It is well known that hormonal changes occur at menopause, but that not all women experience the same symptoms – and some experience none that are bothersome enough to seek treatment. For example, despite similar endocrine characteristics to US women, Mayan women from the Yucatan did not report hot flashes or other symptoms [31]. Thus, hormonal changes alone are not evidence of disease risk. Symptoms such as hot flushes (subjective illness) cannot always be objectively measured, evidenced by a lack of 1:1 concordance between subjective and objectives measures [32,33]. This raises questions about perception and physiology as well as scientific ‘objectivity’, thus opening the door to alternative approaches. 3.2. Holistic perspective on CAM Because “experience is mediated through our bodies and deeply embedded in cultural context” (p. 21) [7], to fully understand the experience of menopause requires a broad understanding of the cultural context including physical and social environments that may mediate a woman’s gene expression (through epigenetics) or the gene expression of her microbiome, which in turn affects physiological functioning. Associated physical experiences (whether irregular menstrual periods, cessation of periods, or hot flushes) may be experienced differently, depending on individual perception, physical environment, and psychological and sociocultural filters (including medicalization) that are applied to bodily sensations. Attitudes toward menopause vary by demographic characteristics and menopausal status, but generally range from

neutral to positive in most populations studied, with negative attitudes correlated with depression [34,35]. Women’s views on menopause vary from seeing it as a medical condition requiring treatment to a natural transition [36]. Physician understanding of and respect for these diverse views will enable more effective treatment of the whole person. Biomedical models of the human body often lead to treating each organ and person in isolation, and looking for universal treatments that will cure all people with the same symptoms or biomarkers. However, CAM often recognizes multiple pathways and treatments. Alternative healing modalities such as mind-body and diet-related treatments have been perceived as contrasting with the aggressive ethos of allopathic medicine, challenging authoritative and paternalistic approaches to healing, and have been particularly appealing to women and minorities [7]. Throughout history, women healers, particularly those who were herbalists or ascetics, have been marginalized and even persecuted as witches [7]. It is against that historical background that women may choose to seek CAM and also be less likely to report its use to their providers. Women choosing CAM may not only be culturally marginalized, but also economically marginalized. Lower SES correlates with lower satisfaction with conventional medical practitioners [37], suggesting that socioeconomic inequality may play a role in women’s use of CAM, and also their reluctance to discuss it with their providers. Thus, for providers committed to improving all women’s health, an awareness of CAM, and associated stereotypes and stigma, is essential. As CAM becomes mainstream and integrated into biomedicine, commercialization may lead it to become “luxuries for the wealthy” [7], decreasing the options available to women with constrained resources, particularly in countries such as the US without universal healthcare. 3.3. Developmental factors over the lifecourse Factors influencing age at menopause, and likely also its experience, begin affecting follicle number and reproductive related physiology in utero, as the number of follicles reaches its maximum at about five months of gestation. Smoking leads to younger menopause (faster depletion of follicles), and may exacerbate

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symptoms. Environmental chemicals like phytoestrogens may exert protective effects on menopausal symptoms [38]. Furthermore, while the efficacy of soy isoflavones is affected by individual and regional differences in gut microflora [39], when and for how long soy is eaten over the lifespan may also affect its efficacy. In many cultures people believe that decisions and factors throughout the lifecourse influence future health. For example, most Chinese women traditionally participated in what is called the zuo yuezi, or “doing the month” in the postpartum period. This month of rest takes place immediately after the birth of a child and significantly restricts a new mother’s diet and movement. It is said to allow yin and yang to restore equilibrium and to affect the health of a woman throughout her life, including improving health at menopause, the third and last change in a woman’s life [40]. CAM appeals to women who want a broader perspective on their health, and providers would benefit from asking women about their explanatory models, following Kleinman [41,42]. 3.4. Placebo effect versus meaning response In biomedical RCTs, the goal is to compare drugs’ effectiveness with that of placebos. A placebo has been defined as “any therapeutic procedure. . .which is given (1) deliberately to have an effect, or (2) unknowingly and has an effect on a symptom, syndrome, disease or patient but which is objectively without specific activity for the condition being treated. . . also used as an adequate control in research” (p. 136) [43]. Much money and effort have been spent to minimize the placebo effect. Yet in most studies of menopausal therapies, the placebo effect is consistently high, up to 59% [44]. Often a source of frustration for drug companies and researchers, this ‘result’ could be, and we argue should be, interpreted in a different light. Menopause, a complex constellation of changes at a unique stage of the lifecourse, may be more responsive to complex cultural interactions between providers and patients, and particularly amenable to interventions involving a placebo, or ‘meaning,’ response. Moerman takes a different approach to the placebo effect, instead focusing on the ‘meaning response’ of any treatment encounter. He defines the ‘meaning response’ as “the psychological and physiological effects of meaning in the treatment of illness” (p. 14) [45], arguing that all aspects of medicine that have meaning, including diagnosis and prognosis, can be important forms of treatment [46]. Just as placebo analgesia can trigger the production of endogenous opiates and be manipulated by opiate antagonist and agonist compounds, so can acupuncture analgesia. Thus, just because treatments like acupuncture may report no more than placebo effect, this does not mean that they are ineffectual [46]. The meaning response is a “genuine and powerful healing force in its own right” (p. 25) [7] that biomedical practitioners would do well to study and exploit to increase their effectiveness as healers. Learning more about CAM options that women may be interested in, or already trying, may improve providers’ rapport and meaning response ‘rate’, whether or not they themselves integrate CAM into their practice.

Black cohosh has been part of the traditional North American pharmacopoeia for many years [49], and has traditionally been used to treat dysmenorrhea, hot flashes and other symptoms associated with menopause [50]. It is one of the most commonly used herbal supplements among menopausal women, although most studies have been inconclusive regarding efficacy for menopausal symptoms [51]. Isoflavones are phytoestrogens (plant compounds that exert estrogenic activity) that are alternatives to HRT [52]. Due to variation in methodology, amounts and forms of isoflavones studied, outcomes measured, and possibly individual differences in microbiome and metabolism, literature on phytoestrogens as treatment for alleviation of menopausal symptoms has been inconsistent [53]. However, recent meta-analyses have demonstrated that isoflavones reliably decrease hot flush frequency [52,53]. Isoflavones must be metabolized by intestinal bacterial enzymes to be absorbed. Individual differences in microbiome lead to different metabolites: for example, only 30–50% of Western women can produce equol, while 80–90% produce O-DMA [54]. Since equol-producing women may benefit more fully from the intake of isoflavones, this may account for discrepancies in reported isoflavone efficacy in addressing menopausal symptoms [55]. 4.2. Mind-body practices

4. Case studies of CAM

If the mind can exert effects on how symptoms are viewed and experienced, and if treatments have significant psychological as well as physical responses, then mind-body therapies may be beneficial in the alleviation of menopausal symptoms. It may be tempting to lump many CAM treatments into mind-body healing modalities – but although Western Cartesian thinking draws lines between mind and body, most cultures do not, and scientific evidence in neuroscience and gut-brain interconnections [56,57] make it clear that such lines cannot be drawn easily. Stress has been shown to have a deleterious effect on many physical and psychological aspects of health, and can also exacerbate disorders and diseases such as depression and heart disease [58]. Stress and other cognitive factors have been shown to increase rates and severity of reported menopausal symptoms [59]. Chronic stress can also lead to lifestyle choices (such as smoking and compulsive eating) that increase susceptibility to diseases such as cardiovascular disease [60]. A growing body of research suggests that active meditation practices such as yoga, tai chi, and qi gong, all traditional forms of meditation involving deliberate movement, are safe and effective alternatives for reducing insulin resistance and related physiological risk factors for cardiovascular disease, and for improving mood, well-being, and sleep as well as decreasing sympathetic activation in peri- and post-menopausal women [61]. Yoga has been shown to have a beneficial effect on psychological symptoms in menopausal women [62]. Tai Chi has been reported to reduce stress and may be effective in slowing osteoporosis in menopausal women [63]. Additionally, since these mind-body therapies are typically performed in groups, they also offer social support, a factor that significantly reduces risk of cardiovascular disease as well as psychological disorders such as depression [61].

4.1. Natural products

4.3. Traditional Chinese medicine (TCM)

Although natural products are often considered to be CAM, it is important to recall that much of our pharmacopeia is derived from botanical sources [47] and that most uses of plant-derived drugs are consistent with their original ethnopharmacological purposes [48]. The two most widely used herbal treatments for menopause in the West include black cohosh and isoflavones derived from soy or red clover.

TCM’s history extends back 3000 years, and includes multiple modes of treatment such as herbal medicine, acupuncture, massage, and meditation [64]. TCM is used both on its own and as a complement to western biomedicine and its popularity has grown both within China and internationally [64]. In TCM, menopausal symptoms result from dysregulation of organs such as the kidney, liver, heart, and spleen, due to a destabilization of the body’s ele-

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mental forces (e.g., excess fire), and “blood stasis, qi stagnation, and phlegm-dampness.” This destabilization leads to an imbalance of yin and yang forces within the body [65]. Individual presentations differ, and thus each treatment plan should be individualized [65]. In a review of 23 studies examining outcomes of women who used Chinese Herbal Medicine (CHM) to treat menopausal symptoms, 17 reported beneficial results of using CHM (most commonly reduction of hot flushes), while others reported no effect [65]. In all studies, standardized Western diagnosis of menopausal symptoms was used in addition to TCM Zheng differentiation diagnosis [65]. Assessment of TCM’s effectiveness is limited by study design rigor and a publishing bias towards positive results [65]. Dong Quai or Angelica sinensis is a well-known herb used in China and Japan to treat a variety of women’s health problems including menopause [66]. A herbal decoction of Astragali Radix (AR) and Angelicae Sinensis Radix (ASR) known as Danggui Buxue Tang (DBT) is commonly used to treat menopausal irregularity in women [66], and has been shown to exhibit significant estrogenic properties in vitro [66,67] as well as estrogen receptor-independent activity [66]. In women experiencing non-surgical menopause, acupuncture helped reduce hot flash frequency and severity, and had a beneficial effect on other psychosocial, physical, sexual, and vasomotor symptoms [68]. A meta-analysis of 12 high quality RCTs of acupuncture for sleep disorders in postmenopausal women found a positive effect on sleep disorders [69], a common complaint at menopause [2]. In a recent placebo-controlled study of combined CHM and TCM-based psychotherapy (including any therapeutic intervention to increase a patient’s sense of well-being), positive outcomes were observed for treating menopausal syndrome categorized as KidneyYin/Kidney-Yang deficiency pattern [70].

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of the Kampo treatment Keishibukuryogan performed among US women, which showed no significant differences in effects on hot flushes compared to placebo [78]. The authors suggest that participants’ expectations that herbal medicine will work may have contributed to a greater meaning response [45]. Additionally, use of Kampo for menopausal women with hot flashes regardless of Kampo sho (or constitutional state) may lead to mismatch of treatment, consistent with observed high rates of GI side effects [78]. Keishibukuryogan best fits women with hiesho (chilliness) [79], a symptom that few Westerners report, and ouketsu (metaphoric blood stagnation). Thus, future studies of CAM should use both biomedical and CAM diagnostic systems [80] for diagnosis and assessment. Most importantly, this study suggests the potential power of Moerman’s meaning response. Given that many women seek CAM due to lack of efficacy of biomedical treatments, or cultural or economic marginalization, biomedical practitioners who make an effort to learn about CAM and ask patients about their CAM use or interest may dramatically improve the patient-provider relationship and rapport, thus harnessing the power of meaning imbued in the clinical encounter. By working with women to integrate their CAM-related health seeking behaviors and treatments, providers may give an added boost to the efficacy of their own biomedical treatments. Contributors MM designed the scope and organization of the review. DT conducted the initial literature review and drafted the initial manuscript. MM conducted additional literature review. MM supervised the writing and critically edited and revised the manuscript, and created the figure. Both authors approved the final manuscript for submission.

4.4. Japanese Kampo Conflict of interest Kampo, or Traditional Japanese Medicine, is used by over 90% of gynecologists in Japan [71] and has become almost fully integrated into biomedical treatments due to its perceived high quality and safety [72]. Kampo is a derivative of TCM and was introduced from China in the 5th century CE, although its use did not become widespread until the 15th century [72]. Kampo establishes an interrelationship between psychological and physical experiences, making no distinction between mind and body. Therefore, like TCM, it is highly individualized [73]. In Kampo, diagnosis of menopausal symptoms is based on Yin-Yang, heatcold, repletion-vacuity patterns or image of qi, blood, and fluids [73]. The most commonly reported Sho, or Kampo diagnoses, in women who reported menopausal symptoms are abnormal fluid metabolism, qi regurgitation, and blood stagnation [73]. A comparative study examining the effects of three major Kampo formulae (Tokishakuyakusan, Kamishoyosan, and Keishibukuryogan) on Japanese peri- and postmenopausal women found that all three were effective in improving problematic sleep patterns [74,75]. Keishibukuryogan lowered systolic and diastolic blood pressure, pulse rate, and resting energy expenditure of women with high blood pressure [76], and Tokishakuyakusan effectively alleviated headaches and depression in menopausal-aged women [77]. 5. Conclusions One of the challenges of assessing the effectiveness of CAM is the individualized nature of illness patterns and associated treatments. Few western biomedical practitioners have the training in TCM or Kampo, herbal medicine or even mind-body therapies, to implement treatment plans. The challenges of introducing elements of CAM from one culture into another were highlighted by a RCT

The authors declare no conflict of interest. Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Provenance and peer review This article has undergone peer review. Acknowledgments The authors would like to thank Dr. Kenji Watanabe and the members of the Keio University School of Medicine Center for Kampo Medicine for references provided about Kampo. References [1] M.K. Melby, L.L. Sievert, D. Anderson, C.M. Obermeyer, Overview of methods used in cross-cultural comparisons of menopausal symptoms and their determinants: guidelines for Strengthening the Reporting of Menopause and Aging (STROMA) studies, Maturitas 70 (2) (2011) 99–109. [2] D. Anderson, M.K. Melby, L.L. Sievert, C.M. Obermeyer, Methods used in cross-cultural comparisons of psychological symptoms and their determinants, Maturitas 70 (2) (2011) 120–126. [3] D. Anderson, L.L. Sievert, M.K. Melby, C.M. Obermeyer, Methods used in cross-cultural comparisons of sexual symptoms and their determinants, Maturitas 70 (2) (2011) 135–140. [4] M.K. Melby, D. Anderson, L.L. Sievert, C.M. Obermeyer, Methods used in cross-cultural comparisons of vasomotor symptoms and their determinants, Maturitas 70 (2) (2011) 110–119.

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