Evidence-Based Complementary and Alternative Medicine

Review Article

Efficacy and Side Effects of Chinese Herbal Medicine for Menopausal Symptoms: A Critical Review

Table 1

Summary of findings of included randomized controlled trials of CHM for menopausal symptoms.

(a)


Study	Number of case treatment/comparison	Age (year) treatment/comparison	Duration	Chinese herbal medicine, form and dose	Comparator
Study	Number of case treatment/comparison	Age (year) treatment/comparison	Duration	Chinese herbal medicine, form and dose	Placebo	Positive comparator

Hirata et al.,1997 [53]	35 (4)/36 (6)	52.2 ± 4.0/52.6 ± 6.0	6, 12, 24 weeks	Dong quai root, granular powder, 4.5 g/day	Yes	No

Woo et al.,2003 [54]	PL: 47 (5) HRT: 48 (2) No treatment: 41 (2)	PL: 57.4 ± 4.6 HRT: 56.2 ± 4.9 No treatment: 57.2 ± 4.8	3 months	Pueraria lobata (PL) powder, 100 mg/day	No	HRT: Premelle 1#/day

Haines et al.,2008 [55]	50 (5)/50 (11)	52.8 ± 4.9/51.2 ± 4.6	6 months	Dang Gui Bu Xue Tang (DBT) capsule 3 g/day	Yes	No

Davis et al.,2001 [56]	42 (14)/36 (9)	56.3 (54.3–58.3)/ 54.1 (52.6–55.5)	12 weeks	CHM granule	Yes	No

Plotnikoff et al., 2012 [34]	Low: 62 (11) High: 57 (13) Placebo: 59 (1)	Low dose: 53.7 ± 0.38 High dose: 53.6 ± 0.49 Placebo: 53.3 ± 0.38	12 weeks	TU-025 (keishibukuryogan) capsule, 7.5 g/day (low dose), 12.5 g/day (high dose)	Yes	No

Yasui et al.,2009 [57]	38 (3)/38 (6)	51.4 ± 5.1/50.5 ± 5.4	6 months	Kamishoyosan 7.5 g	No	Paroxetine 10 mg/day

Wiklund et al.,1999 [58]	193 (3)/191 (2)	53.3 ± 4.0/53.6 ± 4.0	16 weeks	Ginseng extract capsule 200 mg/day	Yes	No

Grady et al.,2009 [59]	Low: 71 (1) High: 75 (1) Placebo: 71 (2)	Low: 53.9 ± 2.6 High: 53.6 ± 3.0 Placebo: 53.7 ± 2.8	4, 8, 12 weeks	MF101 powder, 5 g/day MF101 powder, 10 g/day	Yes	No

Chen et al.,2003 [60]	37 (13)/25 (11)	50.17 ± 3.41/52.14 ± 5.33	16 weeks	Jia-Wey Shiau-Yau San (JWSYS), powder, 4 g, tid/day	No	Premelle 1^#/day^▲▲

郑 Zheng et al.,2009 [61]	CHM: 30 (0) TCM package: 35 (0) Placebo: 20 (0)	CHM: 51.40 ± 2.57 TCM package: 51.17 ± 2.82 Placebo: 50.65 ± 2.32	4, 8, 12 weeks	Gengnianle Granule, 10 g, bid/day	Yes	TCM package^▲▲▲

韦 Wei and Luo,2007 [62]	60 (0)/30 (0)	40–55	3 months	Qianjinbayin 3 g bid/day	No	Premarin 0.625 mg/day + Medroxyprogesterone 6 mg/day (15th–28th day)

Qu et al.,2009 [63]	21 (0)/26 (0)	48.7 ± 8.1/50.4 ± 9.3	12 weeks	Gengnianle decoction 200 mL/day	No	Tibolone 2.5 mg/day

Chang et al., 2012 [64]	31 (2)/33 (1)	53.2 ± 5.7/54.1 ± 5.9	6, 12 weeks	EstroG-100, 1^# bid/day	Yes	No

Kim et al., 2012 [65]	36 (5)/36 (4)	52.98 ± 3.04/55.01 ± 3.67	12 weeks	Red ginseng capsule 1 g tid/day	Yes	No

Hsu et al.,2011 [66]	25 (0)/25 (0)	51.92 ± 2.97/53.08 ± 3.00	6, 12 months	Dioscorea extracts 12 mg bid/day	Yes	No

Kwee et al.,2007 [67]	CHM: 10 (1) HRT: 11 (0) Placebo: 10 (0)	CHM: 53.2 (51.5–55.0) HRT: 53.6 (50.0–57.3) Placebo: 54.9 (51.6–58.2)	12 weeks, plus 4-week followup	(i) Modified Zhi Bai Di Huang Wan (ii) Individualized hydrophilic concentration	Yes	Premelle 1^#/day

陈 Chen et al.,2005 [68]	77 (12)/70 (12)	50.79 ± 4.45/50.43 ± 4.16	1, 3 months	Kuntai capsule 2 g tid/day	No	E₂V 0.5 mg/day^▲▲▲▲

楼 Lou et al.,2009 [69]	80 (11)/30 (3)	52.69 ± 3.12/51.85 ± 2.92	8 weeks	Xian ling gu bao capsule 3^# bid/day	Yes	No

王 Wang et al.,2006 [70]	CHM: 111 (—) CHM + qing zhi: 105 (—) Qing zhi: 104 (—) Placebo: 104 (—)	No detail^▲	4, 8, 12 weeks	Geng nian ning C:C tid/day for kidney yin deficiency Bushen oral liquid, 1 bottle bid/day for kidney yang deficiency	Yes	CHM + Chinese medical qing zhi therapy^{▲▲▲▲▲} Chinese medical qing zhi therapy

吴 Wu et al.,2009 [71]	359 (23)/120 (14)	45–55	8 weeks	Jing qian ping granule 4 g tid/day	Yes	No

李 Li et al.,2009 [72]	188 (53)/189 (96)	48.8 ± 2.93/48.6 ± 2.74	2 years	Bushen Zhuanggu granule 100 g bid/day × 6 months, then 100 g/day	No	Premarin 0.625 mg/day + Medroxyprogesterone 2 mg/day

李 Li et al.,2008 [73]	72 (0)/36 (0)	49.25 ± 2. 38/49.15 ± 2.68	3 months	Gengnianningshentang decoction	No	Vit E 100 mg bid + oryzanol 20 mg tid

刘 Liu et al.,2011 [74]	30 (5)/30 (4)	50.63 ± 3.8/50.63 ± 4.65	12 weeks	Ziyin Jianghuo Fang (ZYJHF) granules	Yes	No

Total amount	1837/1609	//	/	/	/	/

—: did not report.
^▲Including patients with age from 45 to 55, according to the defined inclusion criteria published by Chinese Ministry of Health, 1997 [75].
^▲▲Premelle: 1 tablet includes 0.625 mg conjugated oestrogen, 5 mg medroxyprogesterone.
^▲▲▲TCM package: CHM + Chinese medical psychological therapy + Taiji.
^▲▲▲▲E₂V: estradiol valerate.
^{▲▲▲▲▲}Chinese medical qing zhi therapy: Chinese medical psychological therapy, 情志疗法.
/: blanket.

(b)


Study	Outcome measure	Outcomes			Efficacy
Study	Outcome measure	Treatment versus placebo/no treatment	Treatment versus positive comparator	Treatment versus baseline

Hirata et al.,1997 [53]	(a) Kupperman Index (b) Diary of number of vasomotor symptoms	No significant improvement for (a) and (b)	/	About 25%–30% reduction for (a) and (b), score of (a) from to (), number of vasomotor episodes per week from to ()	No

Woo et al.,2003 [54]	(a) Menopausal symptoms questionnaire (b) Short Form 36 Health Survey (c) Mini-Mental State Examination (MMSE)	No improvement for majority items of (a) and (b); more improvement for cognitive function	Similar change for (a), (b), and (c)	No improvement for five domains of (a); for (b), percentage change for physical functioning, for role physical, for bodily pain, for general health, for vitality, for social functioning, for role emotional, and for mental health; *percentage increase for (c)	No

Haines et al.,2008 [55]	(a) Self-reported daily diary for vasomotor symptoms (b) Menopause-specific quality of life	No significant difference for mild, moderate, and severe hot flushes as well as night sweats of (a); similar improvement for four domains of (b)	/	Improvement for number of mild hot flushes from to per month (); improvement for sexual domain of (b) from to ()	No

Davis et al.,2001 [56]	(a) Diary of the frequency of vasomotor symptoms (b) Menopause-specific quality of life	The frequency of vasomotor symptoms reduced but with similar improvement; similar reduction for scores of four domains of (b)	/	More than 40% reduction in the frequency of vasomotor symptoms (); improvement for physical, vasomotor, and sexual domains of (b)	No

Plotnikoff et al., 2012 [34]	(a) Daily Mayo Hot Flash Symptom Diary; (b) Greene Climacteric Scale; (c) Pittsburgh Sleepiness Quality Scale	Similar improvement for (a), (b), and (c) without significant difference ()	/	40% Improvement for (a) in low-dosage group, 38% in high-dosage group (); significant reduction for the mean scores of (b) (); *improvement for (c) and its subscales (), except sleep medication use	No

Yasui et al.,2009 [57]	Greene Climacteric Scale	/	Less improvement for psychological (), vasomotor()and total score (), no difference for somatic subscore ()	Improvement for psychological, somatic, and vasomotor subscores and total score ()	Unconcluded

Wiklund et al.,1999 [58]	(a) Psychological general well-being Index; (b) women’s health questionnaire; (c) visual analogue scales	Slightly better overall symptomatic relief (); significant better improvement in depression and well-being subscales (); *no significant effects for (b) and (c) or the physiological parameters, including vasomotor symptoms	/	Improvement for total score of (a) and anxiety, depression, well-being, self-control, health, vitality subscores; improvement for vasomotor and somatic symptoms, sleep and menstrual problems, depression, anxiety, attraction, cognitive function scores and total score of (b); *improvement for total score and vasomotor, emotional symptoms of (c), reduction of vasomotor from to ()	Yes

Grady et al.,2009 [59]	(a) Diary of the frequency and severity of vasomotor symptoms; (b) Short Form 36 Health Survey; (c) Female Sexual Function Index	For high-dose group, 33% greater improvement for frequency of mild hot flush (); 67% reduction in the number of awake-sleep by hot flushes per week (); 16.2% more improvement for 50% reduction of hot flushes ()	/	In high-dosage group, 48% reduction for number of hot flushes per week, 67% reduction for number of awake sleep, and 47% for 50% reduction of frequency of hot flushes, respectively 37%, 58%, and 39% in low-dosage group, 37%, 44%, and 31% in placebo group	Yes

Chen et al.,2003 [60]	Greene Climacteric Scale	/	Similar improvement for psychological (anxiety and depression), somatic and vasomotor subscores as well as total score (); less improvement for sexual dysfunction ()	Improvement for psychological, anxiety, depression, somatic and vasomotor subscores and total score ()	Yes

郑 Zheng et al.,2009 [61]	(a) Modified Kupperman Index; (b) Chinese Medical Symptoms Scale	Improvement for total scores of two scales ()	less reduction than TCM package for total scores of (a) and (b) ()	Improvement for (a) and (b) at weeks 8 and 12 ()	Yes

韦 Wei and Luo,2007 [62]	Modified Kupperman Index	/	Similar for total score ()	Improvement for total score from to ()	Yes

Qu et al.,2009 [63]	Hamilton Depression Scale	/	No significant difference for total score (); inimitably improved insomnia middle and anxiety (somatic), no improvement for work and activities, agitation	Improvement for depressed mood, feeling of guilt, suicide, insomnia early, insomnia middle, anxiety (psychological and somatic) subscores ()	Yes

Chang et al., 2012 [64]	Kupperman menopause Index	Magnificently improved vasomotor, numbness and tingling, insomnia, nervousness, feeling blue and depressed, dizzy spells, tired feelings, rheumatic pain, sensation of crawling on the skin, vaginal dryness (), no improvement for headache and palpitation ()	/	Improvement for all subscales at week 12 ()	Yes

Kim et al., 2012 [65]	(a) Kupperman Index; (b) Menopause Rating Scale	Better for hot flash subscore () and total score of (a) (); significant reduction for total score () but no improvement for hot flash of (b) ()	/	Improvement for total score of (a) from to (), hot flash from to (); improvement for total score of (b) from to (), hot flash from to ()	Yes

Hsu et al.,2011 [66]	Greene Climacteric Scale	More improvement for feeling tense or nervous (), insomnia (), excitable (), musculoskeletal pain () after 12 months	/	More than 90% improvement in almost all parameters (except sexual function) at months 6 and 12	Yes

Kwee et al.;2007 [67]	(a) Diary for frequency of vasomotor symptoms; (b) Short Form 36 Health Survey	Improvement for hot flushes with 29% greater average score, more efficacy for weeks 5, 7–11 ()	Less improvement for hot flushes with 50% average score, especially at weeks 4–13 (); no improvement for hot flush reduction of (b)	Improvement for score of (a) at weeks 5, 7–11, no improvement for (a) and (b) at week 16	Yes

陈 Chen et al.,2005 [68]	Modified Kupperman Index	/	Similar improvement for hot flush score and total score ()	Improvement for total score from to	Yes

楼 Lou et al.,2009 [69]	(a) Chinese Medical Symptoms Scale	More reduction for total scores of (a) ()	/	Improvement for total score of (a) from to ()	Yes

王 Wang et al.,2006 [70]	(a) Modified Kupperman Index; (b) Chinese Medical Symptoms Scale	More improvement for total score of (a) at 8th week () but not better at 12th week (); better for total score of (b) at 8th and 12th weeks ()	*More improvement for total score of (a) and (b) ()	—	Yes

吴 Wu et al.,2009 [71]	(a) Chinese Medical Symptoms Scale; (b) modified Kupperman Index	More improvement for total scores of (a) and (b) at week 8 ()	/	—	Yes

李 Li et al.,2009 [72]	Kupperman Index	/	Better for total score ()	Improvement for total score from to ()	Yes

李 Li et al.,2008 [73]	Modified Kupperman Index	/	More reduction for total score ()	Improved total score from to ()	Yes

刘 Liu et al.,2011 [74]	(a) Number of hot flushes and sweat; (b) Chinese Medical Symptoms Scale; (c) Kupperman Index	*More improvement for (a) (), (b) (), and (c) ()	/	Reduction for number of hot flushes per day from to (), number of sweats per day from to (); improvement for total score of (b) from to (); *improvement for total score of (c) from to ()	Yes

(c)


Study	Adverse events/side effects	Thickness of endometrium	Zheng differentiation	Prescriptions

Hirata et al.,1997 [53]	Burping, gas, headache (similar to placebo)	No increase at 24 weeks, no difference to placebo	No	Dang gui (Angelica sinensis) root

Woo et al.,2003 [54]	Urticaria	—	No	Ge gen (Pueraria lobata)

Haines et al.,2008 [55]	Constipation, epigastric discomfort, hypercholesterolemia, per rectum bleeding (SAE) (no difference to placebo)	—	No	Dang gui (Angelicae sinensis) : huang qi (Astragalus membranaceus) = 1 : 5

Davis et al.,2001 [56]	Abdominal bloating, lower abdominal pain and loose stools, headache, joint pain, dizziness (no difference to placebo)	—	No	Shu di huang (Rehmannia glutinosa) 15 g, shan zhu yu (Cornus officinalis) 10 g, shan yao (Dioscorea opposita) 12 g, ze xie (Alisma orientalis) 8 g, dan pi (Paeonia suffruticosa) 8 g, fu shen (Poria cocos) 12 g, chen pi (Citrus reticulata) 5 g, di gu pi (Lycium chinensis) 20 g, he huan pi (Albizia julibrissin) 15 g, suan zao ren (Zizyphus jujuba) 10 g, han lian cao (Eclipta prostrata) 15 g, and nu zhen zi (Ligustrum lucidum) 10 g

Plotnikoff et al., 2012 [34]	Prevalent diarrhea (more than in placebo)	—	No	Rou gui (Cinnamomum cassia Blume), bai shao (Paeonia lactiflora Palls), tao ren (Prunus persica Batsch), fu ling (Poria cocos Wolf), and dan pi (Paeonia suffruticosa Andrews)

Yasui et al.,2009 [57]	Diarrhea	—	No	Angelica root, Atractylodis lanceae rhizome, Peony root, Bupleurum root, Hoelen, Glycyrrhiza root, Moutan bark, Gardenia fruit, Ginger rhizome, and Mentha herb

Wiklund et al.,1999 [58]	Headache/migraine, diarrhea/gastrointestinal system disorders, nausea, seven SAE (no difference to placebo)	No increase	No	Standardized extracts of ren shen (Ginseng root)

Grady et al.,2009 [59]	Loose stools, vaginal bleeding, idiopathic pancreatitis (SAE) (no difference to placebo)	No difference among three groups	No	Ban zhi lian (Herba Scutellaria barbata) 30 g, shan dou gen (Radix Sophora subprostratae) 15 g, zhi mu (Radix Anemarrhenae) 12 g, hei dou (Semen Glycine sojae) 20 g, gan cao (Radix Glycyrrhiza) 8 g, da huang (Rhizoma Rhei) 8 g, fu xiao mai (Fructus Tritici levis) 15 g, huang qi (Radix Astragali) 12 g, sheng di huang (Radix Rehmannia) 12 g, nu zhen zi (Fructus Ligustri lucidi) 15 g, suan zao ren (Semen Zyziphi spinozae) 10 g, lian zi xin (Plumula Nelumbinis) 10 g, fu ling (Poria Cocos) 10 g, ze xie (Rhizoma Alismatis) 10 g, mu dan pi (Cortex Moutan radicis) 8 g, shan zhu yu (Fructus Corni) 10 g, huai niu xi (Radix Achyranthis) 10 g, mu li (Concha Ostrea) 12 g, tian men dong (Radix Asparagi) 12 g, ge gen (Radix Pueraria) 10 g, bai zhu (Radix Atractylodis macrocephala) 10 g, and yin yang huo (Herba Epimedii) 8 g

Chen et al.,2003 [60]	Bloated abdomen, unusual vaginal bleeding, nausea and cough (no mention for the difference)	—	No	Dang gui (Angelicae Radix) 4 g, bai zhu (Atractylodis Rhizoma) 4 g, bai shao (Paeoniae Radix) 4 g, chai hu (Bupleuri Radix) 4 g, fu ling (Poria cocos Wolf) 4 g, gan cao (Glycyrrhizae Radix) 2 g, mu dan pi (Moutan Bark) 2.5 g, zhi zi (Gardeniae Fructus) 2.5 g, gan jiang (Zingiberis Rhizoma) 4 g, and bo he (Menthae Herba) 2 g

郑 Zheng et al.,2009 [61]	Diarrhea (one case)	—	No	Huang lian (Rhizoma Coptidis), mai dong (Radix Ophiopogonis), mu dan pi (Moutan Bark), and other herbs

韦 Wei and Luo,2007 [62]	—	(i) No increase in treatment group (ii) Increase in hormone therapy group	No	Qian jin ba (Moghania philippinensis), ge jei (Gekko gecko), mei gui hua (Rosa rugosa), nuo dao gen (Radix Oryzae Glutinosae), and other herbs

Qu et al.,2009 [63]	No serious side effect	—	No	Zhen zhu mu (C. Margaritifera) 15 g, suan zao ren (Semen Z. Spinosae) 8 g, bai zi ren (Semen Platycladi) 12 g, yuan zhi (of radix polygalae) 10 g, he huan pi (cortex albiziae) 8 g, huang qi (radix astragali) 15 g, xi yang shen (radix codonopsis) 10 g, shan yao (radix dioscoreae) 15 g, tu si zi (semen cuscutae) 15 g, and nv zhen zi (fructus L. Lucidi) 10 g

Chang et al., 2012 [64]	No adverse events	—	No	Cynanchum wilfordii, Phlomis umbrosa, and Angelica gigas

Kim et al., 2012 [65]	—	—	No	Hong shen (red ginseng)

Hsu et al.,2011 [66]	No serious adverse events except soft stools, nausea (mild and transient) (no mention for the difference)	No increase	No	Shan yao (Dioscorea alata)

Kwee et al.,2007 [67]	No serious adverse events	—	Kidney yin deficiency	Zhi mu (Rhizoma Anemarrhenae) 5.1%, huang bai (Cortex Phellodendri) 5.1%, shu di huang (Radix Rehmanniae praeparata) 20.5%, shan zhu yu (Fructus Corni) 10.3%, shan yao (Rhizoma Dioscoreae oppositae) 10.3%, fu ling (Sclerotium Poriae albae) 7.7%, duan long gu (Os Draconis ustum) 10.3%, duan mu li (Concha Ostreae usta) 10.3%, mu dan pi (Cortex Moutan radicis) 7.7%, and ze xie (Rhizoma Alismatis) 7.7%, and gou qi zi (Fructus Lycii) 5%—without details for the modification

陈 Chen et al.,2005 [68]	Gastrointestinal symptoms, breast distension and pain, and vaginal bleeding (no mention for the difference)	No increase	Yin deficiency with excessive fire	Shu di huang (Radix Rehmanniae praeparata), huang lian (Rhizoma Coptidis), bai shao (Radix Paeoniae), e jiao (Colla Corii asini), huang qin (Radix Scutellariae), and fu ling (Poria)

楼 Lou et al., 2009 [69]	No serious side effect	No increase	Yin deficiency with excessive fire	Yin yang huo (Herba Epimedii), other herbs (without details)

王 Wang et al.,2006 [70]	No serious side effect	No increase	Kidney yin deficiency/kidney yang deficiency	Geng nian ning capsule: shu di huang (Radix Rehmanniae praeparata), fu ling (Poria), huang lian (Rhizoma Coptidis), e jiao (Colla Corii asini), other herbs bu shen oral liquid: shu di huang (Radix Rehmanniae praeparata), nu zhen zi (Fructus Ligustri lucidi), yin yang huo (Herba Epimedi), and other herbs (without details)

吴 Wu et al.,2009 [71]	Stomach disorder, breast distension (no difference to placebo)	—	Yin deficiency with excessive liver qi	Bai shao (Radix Paeoniae), xiang fu (Rhizoma Cyperi), chuan lian zi (Fructus Toosendan), chai hu (Radix Bupleuri), and other six herbs

李 Li et al.,2009 [72]	No serious adverse events	—	Spleen-kidney deficiency with blood stasis	Shan zhu yu (Cornus officinalis), lu jiao jiao (Colla Cornus Cervi), gui ban jiao (Chinemys reevesii), rou gui (Cinnamomum cassia Blume), ba ji tian (Radix Morindae officinalis), yin yang huo (Herba Epimedi), bai shao (Radix Paeoniae), san leng (Rhizoma Sparganii Stoloniferi), ze xie (Rhizoma Alismatis), shui zhi (Hirude nipponica Whitman), yu jin (Curcuma aromatica Salisb), gu sui bu (Rhizoma Drynariae), shan yao (Dioscorea opposita), and other herbs (without details)

李 Li et al.,2008 [73]	Headache, dizziness, epigastric discomfort (no difference to vitamin E plus oryzanol treatment)	—	Yin deficiency with excessive fire	Sheng di huang (Radix Rehmannia) 30 g, shan zhu yu (Cornus officinalis) 15 g, nu zhen zi (fructus L. Lucidi) 15 g, han lian cao (Eclipta prostrata) 15 g, gou qi zi (Fructus Lycii) 15 g, tu si zi (semen cuscutae) 15 g, dan shen (Salvia miltiorrhiza) 15 g, di gu pi (Lycium chinensis) 15 g, gui ban (Carapax Testudinis) 15 g, zhen zhu mu (C. Margaritifera) 15 g, wu wei zi (Schisandra chinensis) 10 g, yuan zhi (Radix Polygalae) 10 g, and yin yang huo (Herba Epimedi)10 g

刘 Liu et al.,2011 [74]	—	—	Yin deficiency with excessive fire	Gou teng (Gambir Plant)15 g, lian zi xin (Plumula Nelumbinis) 5 g, huang lian (Rhizoma Coptidis) 3 g, suan zao ren (Semen Z. Spinosae ) 15 g, fu xiao mai (Fructus Tritici levis) 30 g, dan shen (Salvia Miltiorrhiza) 10 g, sheng di huang (Radix Rehmannia) 10 g, and shan zhu yu (Fructus Corni) 9 g