Chinese herbal medicine for menopausal symptoms (2024)

Monitoring Editor: Xiaoshu Zhu, Yuklan Liew, Zhao Lan Liu, and Cochrane Gynaecology and Fertility Group

Western Sydney University, National Institute of Complementary Medicine (NICM), Locked Bag 1797, Penrith, SydneyNew South WalesAustralia, 2751

Herbal Medicines Research and Education Centre, Sydney University, Milperra Family Medicine Centre, SydneyNSWAustralia

Beijing University of Chinese Medicine, Centre for Evidence‐Based Chinese Medicine, 11 Bei San Huan Dong Lu, Chaoyang District, BeijingChina, 100029

Title: Chinese herbal medicines for menopausal symptoms

Review Question: Are Chinese herbal medicines effective and safe for relieving menopausal symptoms?

Background: Menopause usually takes place when a woman is around 51 years of age. Women can experience symptoms such as hot flushes, sweats, poor sleep, joint pains, anxiousness, dry skin and vagin* when the organs which produce female hormones slow down. Usually hormone therapy (HT) is prescribed to reduce the symptoms.

Due to concerns on long term use of HT resulting in adverse effects, women have been looking for alternative treatments to relieve their symptoms. Chinese herbal medicines (CHM) is one of the popular choices. Although CHM has been used for a very long time clinically, its effectiveness and long‐term safety remained unanswered from a scientific perspective.

Study characteristics: This review examined 22 randomised clinical trials where 2902 women took part in the studies; 1499 in the CHM group and 1403 in the control group which might include a placebo (non‐active compound made to look, taste and smell the same as the study compound) or a drug or HT or another CHM formula (different from the one being tested). Most of the studies had a trial period for 12 weeks. The data are current to March 2015.

Key results: We found insufficient evidence that CHM were any more or less effective than placebo or HT for the relief of vasomotor symptoms. Adverse effects were not well reported, some women taking CHM reported mild diarrhoea, breast tenderness, gastric discomfort and an unpleasant taste. Effects on safety were inconclusive.

Quality of the evidence: The quality of the evidence ranged from very low to moderate. The studies did not produce good quality evidence to allow the authors to draw a conclusive statement regarding the effectiveness or safety of CHM.

Summary of findings for the main comparison

Summary of findings 2

Description of the condition

Menopause is defined as the permanent cessation of menses, usually signalling the end of a woman’s reproductive years (Greendale 1999). It is said to have occurred after 12 months of amenorrhoea (the absence of menstrual periods), therefore the time of the final menses can only be determined retrospectively. Menopause may occur naturally as the result of ageing or as a consequence of the following: surgical removal of ovaries, or as a result of radiation, or chemotherapy (Dodin 2013). The mean age of natural menopause is 51 years (Gold 2001; Greendale 1999; Nelson 2008) with most women experiencing menopause with a range of 40 and 58 years of age (NIH 2005). Age at menopause may be affected by various factors such as smoking, socioeconomic status, age at menarche (first menstrual period), parity, previous oral contraceptive use, body‐mass index (BMI), ethnic origin, and family history (Nelson 2008).

Women experience menopause differently; vasomotor complaints such as hot flushes and perspiration being the most commonly reported in the USA and UK, whereas joint pain is a complaint prevalent amongst Asian women (Castel‐Branco 2005; Chim 2002; Dennerstein 2004; Singh 2002). Other common symptoms include loss of libido, dryness and thinning of the skin and vagin*l wall, mood swings and depression, osteoporosis, and insomnia. Variations in these clinical symptoms may occur across ethnic groups (Avis 2001; Geller 2006; Haines 2005; Nelson 2008). Symptoms also tend to fluctuate and their severity varies greatly between individuals, rangingfrom a mere discomfort to severe distress with substantial reduction in the quality of life (Marjoribanks 2012). The average duration of menopausal symptoms is three and a half years (McKinlay 2006), however it can range from five months to 10 years (Leach 2012).

Natural menopause occurs when the ovaries no longer produce eggs (ovulation), and therefore the amounts of the hormones progesterone and oestrogen present in the body decrease significantly.

Description of the intervention

In many countries, women are actively seeking alternative approaches to reduce their menopausal symptoms (Bair 2008; Biddle 2003; Chen 2010; Michelle 2002; Newton 2002). These include vitamins and minerals, plant‐derived dietary supplements, meditation, and traditional Chinese medicine (TCM). TCM is one of the most popular alternative and complementary therapies (Tindle 2005; Xue 2007), with a history of practice exceeding 2000 years. It offers a clear and systematic approach to the management of menopausal symptoms (Scheid 2007). Its therapies, including the use of Chinese herbal medicine (CHM), acupuncture, and specific diets and exercises, are commonly used to relieve menopausal symptoms in Eastern countries (Chen 2010). Recently, the practice of TCM has significantly permeated a broad cross‐section of western communities (Kwee 2007; Zhu 2009).

The forms of CHM preparations are varied; from traditional raw herbs made into a decoction, pills, liniments, plasters and ointments to concentrated powder and liquid extracts prepared by modern pharmaceutical procedures. The routes of administration also differ, either oral, topical, intravenous or injections into specific acupuncture points. Practitioners may choose to select a single herb or a complex formula consisting of several herbal ingredients.

A formula may be used un‐tailored to individual needs and remain unchanged throughout the whole period of clinical intervention; this is known as the standard approach. Conversely, an individualised approach requires prescription of different formulae customised specifically for different individuals or modification of a basic formula during different stages of clinical intervention to respond to clinical changes if present. This is one of the underpinning theoretical constructs of TCM and a number of complementary therapies.

TCM operates under a different theoretical paradigm to the dominant paradigm of Western biomedical science (Zhu 2009). In the case of menopausal symptoms, biomedical science has viewed menopause as the presence of organic conditions (the deficiency of ovaries due to ageing process or various medical interventions), with illness manifesting as changes in structure (e.g. dryness and thinning of skin and vagin*l wall, and osteoporosis) and function of the body (such as hot flushes, poor memory, mood swings), observed at the anatomical and physiological levels, and increasingly reliant on laboratory findings for detection (i.e. increased follicle stimulating hormone (FSH) levels, decreased oestrogen and progestogen levels).

In comparison, TCM regards illness as a syndrome or pattern (Zheng), manifesting as a disparate but mutually related set of signs and symptoms occurring throughout the whole body, and may arise from disharmony of the body (Deng 1983). The syndromes or diagnostic categories of TCM describe clinical patterns of both objective signs and subjective symptoms. Although the term 'menopause' does not appear in historical TCM literature, the clinical manifestations were recognised and considered to be related to hypo‐functions of the kidney. Contemporary Chinese medicine gynaecological textbooks such as Gynaecology in TCM (Zhong Yi Fu Ke Xue ) (Luo 1986) also continue to attribute menopause to kidney function: that is, around the cessation of menstruation, the Kidney Qi gradually declines. The fundamental theories and approaches of TCM, reflecting upon the practice of CHM, determine contemporary scientific research and clinical practice in managing menopausal symptoms.

Another key requirement of traditional treatment with CHM is that the treatment has to be tailored to the individual at the outset as well as modified at different stages of the patient's recovery or illness, since the clinical patterns may change during different stages. Hence, a second and distinct diagnostic process is required, as illness labelling (and therefore the treatment process) differs from conventional medical approaches (Zhu 2009). For example, a menopausal woman at onset of transition, a diagnostic pattern “Deficiency of Kidney Yin Resulting in Empty Heat” may be made in accordance with her clinical manifestations, whilst a pattern of “Deficiency of Kidney Yin and Kidney Yang” may be labelled later on when the postmenopausal stage is attained.

These fundamental theories and approaches of TCM, reflecting on the practice of CHM, determines contemporary scientific research in the field of menopausal symptoms. Therefore, it was our intention to rigorously follow the scientific approaches whilst to fully respect the traditional philosophies and practice of Chinese medicine while conducting this systematic review.

How the intervention might work

Chinese herbal medicine is currently used in public hospitals in China for the treatment of menopause. In the last few decades, much research has investigated the efficacy, possible risks, and adverse effects of CHM for the management of menopausal symptoms. A review of the literature of 485 clinical studies (Liu 2008) in 2008 reported that 185 herbs were used to treat menopausal symptoms. Dang Gui (Radix Angelicae sinensis), a commonly used Chinese herb, was most frequently cited. This herb has traditionally been used to treat dysmenorrhoea, irregular menstruation and as a supportive herb for menopausal complaints (Geller 2006; Luo 1986). Dang Gui is reported to act by enhancing oestrogen production (Amato 2002). Ren Shen (Radix Panax ginseng), another commonly used herb (Kronenberg 2002), has also been reported in several publications (Ososki 2003) to have oestrogen‐like effects on vagin*l mucosa. Its extract has also been found to compete with estradiol (E₂) for oestrogen‐ and progesterone‐binding sites in human myometrial cytosol (Punnonen 1980). This may be due to triterpene saponin, which is a subtype of isoflavone (a type of phyto‐oestrogen) (McBane 2008).

Recommendations for treating menopausal symptoms in the TCM literature are dominated by formulations which usually contain about a dozen herbs with different functions within the TCM framework. The most commonly selected herbal formula is Liu Wei Di Huang Wan, which has been used for more than one thousand years. It is also the most widely used CHM formula for the tonification of the Kidney Yin, as a basic formula for treatment in either pattern of deficiency of Kidney Yin or Kidney Yang (Scheid 2007). Traditional applications listed in the Chinese Pharmacopoeia include hot flushes, night sweating, dizziness, tinnitus, weakness and soreness of limbs and lower back, and fertility dysfunctions (NJUTCM 2006).

In Liu’s review (Liu 2008), the Liu Wei Di Huang Wan formula was the most frequently cited amongst the 73 classic formulae reported in 485 studies. A randomised controlled trial (RCT) conducted by a Dutch research team (Kwee 2007) used Zhi Bai Di Huang Wan (a variation of Liu Wei Di Huang Wan) versus hormone therapy (HT) and placebo to treat menopausal symptoms. The authors concluded that the formula could produce a reduction in frequency of vasomotor symptoms and that overall quality of life was also improved. However, no oestrogen was detected in the herbal formula and the mechanism of the formulation remained uncertain.

Why it is important to do this review

Many questions about menopausal transition and its symptoms have not yet been adequately answered (Nelson 2008). Hormone therapy (HT, oestrogen alone or combined oestrogen with progestogen) is widely used to treat menopausal symptoms (Marjoribanks 2012). However, there are considerable concerns regarding the adverse effects associated with conventional therapies, especially with long‐term use. The major concern is the adverse effects resulting in an increased risk of cardiovascular disease and breast cancer as reported in the Women’s Health Initiative study (Rossouw 2002), as well as other studies (Colditz 2005; Persson 2000; Störk 2004). As outlined in several Cochrane reviews, HThas been associated with an increased incidence of venous thromboembolic events, pulmonary embolus, stroke (Boardman 2015), and gallbladder disease (Marjoribanks 2012). The publication of these results and lack of confidence in pharmacological interventions have resulted in a reduction in the use of HT and an increase in complementary and alternative therapies which may include CHM (Bair 2008; Dodin 2013; Geller 2006; Leach 2012).

Public interest in the use of CHM, as one of the most popular alternatives, for the improvement of menopausal symptoms is likely to increase. Although CHM is generally safe when used properly by qualified practitioners, many herbs and formulae have contraindications, and some can be toxic. Most importantly, the effectiveness and safety of long‐term use of CHM to treat menopausal symptoms is yet to be well developed within the scientific research framework.

Given that the evidence of the safety and effectiveness of Chinese herbs for the treatment of menopausal symptoms is important, there is an urgent need for a systematic review of the available literature so that the unique needs of menopausal women can be addressed and quality of life improved.

Criteria for considering studies for this review

Search methods for identification of studies

Data collection and analysis

Data collection and analysis were conducted in accordance with the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011).

Description of studies

Risk of bias in included studies

Effects of interventions

See: Table 1; Table 2

In terms of comparisons, results in this review are reported according to the following sequence.

• CHM versus placebo

• CHM versus no treatment

  • including CHM + placebo versus placebo

• CHM + conventional therapy (drug as short term) versus placebo + conventional therapy (drug)

• CHM versus conventional therapy (HT)

  • including CHM + placebo versus conventional therapy (HT) + placebo

• CHM versus conventional therapy (drug)

• CHM versus another CHM (different formulations)

• CHM versus acupuncture

See Differences between protocol and review for minor changes and rationale.

The relevant outcomes of each comparison are reported as below.

The primary outcome was modified for clarity as changes of vasomotor symptoms including:

• frequency of hot flushes/night sweats;

• severity of hot flushes/night sweats;

• overall scores of hot flushes/night sweats (i.e. combination of frequency and severity);

• overall scores of vasomotor symptoms (i.e. combination of hot flushes and night sweats).

The secondary outcomes are reported accordingly as below:

• menopausal symptoms measured by different instruments;

• adverse effects;

• quality of life (QoL);

• satisfaction of treatment.

Note: see 'Difference between protocol and review' for the modifications and rationale.

Summary of main results

Data were assessed and findings were reported in line with the rigorous scientific research ideologies and consideration of the fundamental philosophies employed in traditional Chinese medicine (TCM).

Summary of findings

This systematic review of Chinese herbal medicine (CHM) for menopausal symptoms was based on 22 RCTs. There were 2902 perimenopausal and postmenopausal women from different ethnic backgrounds with 90% from a Chinese background. Diagnosis was based on assessment of menopausal scores across the 22 included studies, while nine of the studies also utilised an additional Chinese medicine diagnostic tool.

Except for two studies that evaluated one Chinese herbal formula, 20 trials studied different formulations which consisted of different ingredients with a total of 91 experimented herbs. Amongst them there were 11 of the most commonly used herbs which are very consistent with the clinical literature resources and contemporary clinical practice. Placebo, hormone therapy (HT) and other types of conventional drugs as well as another herbal formula were used as comparisons, however, the majority of the studies used placebo (8/22 studies) and HT (10/22 studies) as a control, this includes one study that used both placebo and HT as controls.

It was noted that when a style of herbal intervention was considered in these included studies, neither a single herb, nor a complete tailored approach (which is the most standard TCM practice) was used. The majority of studies used a standard formula throughout the trial, which is a reflection of the reconciliation between the rigorous scientific methodology and the fundamental TCM philosophies as an effort of integration in contemporary Chinese medicine research.

The most popular length of intervention was 12 weeks, with a few trials having one to four weeks lead‐in period and four to 12 weeks follow‐up. The majority of the interventions used CHM extract in the form of granules.

Although the quality of study design was relatively good as far as many similar CHM clinical trials other than in the area of hot flushes were concerned, there were still serious flaws in the study designs. A large proportion of the included studies (16/22) did not report how allocation concealment was carried out; less than 50% of studies (10/22) were double‐blind trials which influenced partially the primary outcome with less impact on some of secondary outcomes such as changes in the levels of hormones and lipids. Placebo seemed to be used appropriately in terms of its identical appearance and taste to CHM. Intention‐to‐treat (ITT) was not implemented appropriately, only 13/22 studies considered missing and incomplete data. Nevertheless, reporting bias was relatively low, since the majority of studies reported expected outcomes. Many studies did not report full compositions, or full dosages of the investigated formulations, or both. No other potential bias was detected across the included studies.

Several different common menopausal symptoms scores were used. This included numerical results from an individual or a combination of menopausal symptoms and dichotomous data from a combination of menopausal symptoms. A few studies used the same outcome measure such as the Kupperman Index (KI), Menopause‐Specific Quality of Life (MENQOL), Greene Climacteric Scale (GCS) and Menopause Rating Scale (MRS). However for statistical analysis, data were entered and analysed separately, in order to best address the heterogeneity caused by the diversity in terms of assessment tools.

Findings of the CHM effects on menopausal symptoms were summarised in the following aspects.

Vasomotor symptoms: Meta‐analysis of the pooled data found CHM was no better than placebo for vasomotor symptoms measured by frequency and severity of daily hot flushes, and overall scores of vasomotor symptoms by a specific questionnaire. The evidence was rated from low to moderate grade.

With HT as control intervention, pooled continuous data did not show any difference in the overall vasomotor symptoms between the CHM and HT with no data available on the other defined aspects of vasomotor symptoms. The evidence was rated as very low grade.

The rest of defined comparisons reported no data on the primary outcome, i.e. vasomotor symptoms.

Menopausal symptoms: Meta‐analysis of the pooled monthly menopausal symptom scores showed no difference between CHM and HT in continuous data; however the pooled monthly menopausal symptoms scores in dichotomous data set suggested a difference between CHM and HT, in favour of CHM. No pooled data were available from other comparisons on menopausal symptoms.

Adverse effects: The majority of the studies (17 out of 22) evaluated adverse effects; overall, the Chinese herbal formulae were well‐tolerated based on the clinical adverse effects events and the relevant laboratory examinations (haematological and biochemical). Most adverse effects reported were mild to moderate including diarrhoea, tenderness of the breasts, gastric discomfort, and the unfavourable taste of the CHM. The adverse effects symptoms were resolved once the CHM was terminated. Meta‐analysis of the pooled adverse effects in the dichotomous data set showed no difference between CHM and placebo or in the comparisons between CHM and HT or drugs. In summary, it is reasonable to conclude that CHM did not present any higher risk of adverse effects compared with HT, placebo and some pharmaceutical drugs.

Quality of life: Only two studies evaluated this outcome measure by using either the MENQOL or SF‐36. There was no difference between CHM plus placebo and placebo groups.

Satisfaction of treatment: no study assessed this outcome.

Other outcomes: There was a tendency that studies conducted in China were more likely to assess the hormone levels including serum FSH, LH, E₂ and/or progesterone for exploring any possible mechanisms of effectiveness. However these were not outcomes of interest to this review and we have not reported them.

Overall completeness and applicability of evidence

The objective of this review was to evaluate the effectiveness and safety of CHM in perimenopausal and postmenopausal women using the same research methods across the included studies. The participants were perimenopausal and postmenopausal women; various formulae with 11 of the most commonly used herbs investigated with a standard approach. The range of intervention periods varied widely from four weeks to 106 weeks, with the most common duration being 12 weeks. The most commonly used form of herbs is herbal extract as granules for practical purposes. Outcome measures assessed included frequency and intensity of daily hot flushes and night sweats, monthly menopausal symptoms scores, adverse effects, quality of life which were consistent with current practice in menopause research.

However, incomplete reports on formula compositions and dosages, paucity of data on the number of women experiencing adverse events, substantial heterogeneity for primary and secondary outcome measures, flaws in design leading to high risk of bias in allocation, blinding, incomplete outcome data and selective reporting issues made the results inconclusive. Thus, the completeness and applicability of the evidence is limited.

Furthermore, the formulations and herbs varied; there were 21 formulae with 91 herbal ingredients. This limits the applicability of findings in general practice of Chinese herbal medicine, since there are many more formulae and herbs that were not tested in the included studies but are commonly used in day‐to‐day practice. Assessment of an individual's constitution which is often interpreted as Chinese medicine diagnostic patterns also influences applicability of the evidence in this review. For the consumer, it is very important to seek professional advice from a qualified Chinese medicine practitioner.

In addition, the majority of participants were of Chinese background, so results should be interpreted with caution when applied to other ethnic groups.

Quality of the evidence

The quality of the evidence for CHM for menopausal symptoms was affected by inadequate reporting of study methods. Figure 2 and Figure 3 indicate the methodological quality of the trials included in this review based on the review authors' judgements. Many studies did not report full compositions or full dosages of the investigated formulations. Therefore, the quality of the evidence was impacted potentially by the presence of selection bias, performance bias, attrition bias and reporting bias. The quality of the evidence was also influenced by the unexplained high level of heterogeneity between studies, types of herbs experimented and the paucity of data on the number of women experiencing adverse events. Using GRADE criteria, the quality of the body of evidence for comparison of CHM versus placebo was rated from moderate to very low for effectiveness. See Table 1. The quality of the evidence for the comparison of CHM versus HT was rated very low for effectiveness outcomes. See Table 2. The quality of the evidence for adverse effects from above comparisons was graded very low.

Potential biases in the review process

It is notable that there were a few limitations to this review. Although the search strategy was comprehensive, it is possible that some unpublished reports or studies published in languages other than English and Chinese could have been unintentionally missed. Therefore language and publication bias cannot be excluded entirely. Furthermore, the heterogeneity of measures used and study materials tested in the included studies made it difficult to compare across the included studies. The expanded defined outcomes in the review stage may introduce bias in reporting the results.

Agreements and disagreements with other studies or reviews

The main findings of this review do not completely echo the results from previous reviews (Peng 2014; Taylor‐Swanson 2014; Xie 2005; Xu 2012). Whilst this review is likely the most comprehensive systematic review with meta‐analysis, it found little evidence that CHM was any more or less efficacious for the management of menopausal symptoms compared to placebo or HT.

Implications for practice

Based on the findings, this review was unable to draw firm conclusions about the effectiveness and safety of CHM for menopausal symptoms due to inadequate quality of the research evidence.

Implications for research

The review authors would like to acknowledge Helen Nagels, Marian Showell and the team of the Gynaecology and Fertility Group for their guidance and assistance with the preparation of the review, and to Jane Clarke and Michelle Proctor for their involvement in the development of the protocol. We also acknowledge Yunjiao Zhang, a Masters student of Beijing University of Chinese Medicine, for assistance with the data entry from the studies published in Chinese.

This work was partially funded by Grant Number R24 AT001293 from the National Center for Complementary and Alternative Medicine (NCCAM). The contents of this systematic review are solely the responsibility of the authors and do not necessarily represent the official views of the NCCAM or the National Institutes of Health.

Comparison 1

Comparison 2

Comparison 3

Comparison 4

Characteristics of included studies [ordered by study ID]

Characteristics of excluded studies [ordered by study ID]

Internal sources

• Menstrual Disorders and Sub‐fertility Group, New Zealand.

External sources

• University of Western Sydney, National Institute of Complementary Medicine, Australia.

• Beijing University of Chinese Medicine, Other.

• National Center for Complementary and Alternative Medicine (NCCAM), USA.

  $5000: Grant Number R24 AT001293.

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