Meta-analysis on the efficacy of liver-soothing formulas for perimenopausal anxiety and depression

Table 1 PubMed search mode

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1	"Medicine, Chinese Traditional"[Mesh]
2	(("Medicine, Chinese Traditional"[Mesh]) OR ((((((((((((((Zhong Yi Xue[Title/Abstract]) OR (Chung I Hsueh[Title/Abstract])) OR (Hsueh, Chung I[Title/Abstract])) OR (Traditional Medicine, Chinese[Title/Abstract])) OR (Chinese Traditional Medicine[Title/Abstract])) OR (Traditional Chinese Medicine[Title/Abstract])) OR (Chinese Medicine, Traditional[Title/Abstract])) OR (Traditional Tongue Diagnosis[Title/Abstract])) OR (Tongue Diagnoses, Traditional[Title/Abstract])) OR (Tongue Diagnosis, Traditional[Title/Abstract])) OR (Traditional Tongue Diagnoses[Title/Abstract])) OR (Traditional Tongue Assessment[Title/Abstract])) OR (Tongue Assessment, Traditional[Title/Abstract])) OR (Traditional Tongue Assessments[Title/Abstract]))))) OR ((soothing liver[Title/Abstract]) OR (liver-soothing[Title/Abstract]))) OR (Shugan[Title/Abstract])) OR ((((((((((((((xiaoyao) OR (chaihu)) OR (Longdan Xiegan Wan)) OR (Decoction for Calming the Liver and Promoting Qi Circulation)) OR (Qi - Stagnation Stomach Granules)) OR (Consistent Decoction)) OR (Yiguan Decoction)) OR (Yiguan Jian)) OR (Qiju Dihuang Wan)) OR (Sinisan)) OR (Chaihu Shugan San))) OR (Yueju)) OR (Longgu Muli)))
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6	(((((((Angst[Title/Abstract]) OR (Nervousness[Title/Abstract])) OR (Hypervigilance[Title/Abstract])) OR (Social Anxiety[Title/Abstract])) OR (Anxieties, Social[Title/Abstract])) OR (Anxiety, Social[Title/Abstract])) OR (Social Anxieties[Title/Abstract])) OR (Anxiousness[Title/Abstract])
7	"Depression"[Mesh]
8	(((((Depressive Symptoms[Title/Abstract]) OR (Depressive Symptom[Title/Abstract])) OR (Symptom, Depressive[Title/Abstract])) OR (Emotional Depression[Title/Abstract])) OR (Depression, Emotional[Title/Abstract])) OR (Depressed[Title/Abstract])
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10	#3 AND #4 AND #9

Table 2 Basic characteristics of 12 included studies

Ref.	Country	Duration of study	Sample size (case)		Average age (years)		Interventions		Duration of intervention	Outcome index
			T	C	T	C	T	C
Chen et al[12], 2021	China	September 2014 to August 2016	136	140	50.8 ± 3.9	50.6 ± 4.5	Xiangshao granules	Placebo	8 weeks	(1) (2) (11)
Du et al[13], 2014	China	December 2012 to December 2013	90	90	45.30 ± 2.81	46.09 ± 2.45	Xiaoyao pill	Placebo	8 weeks	(1)
Qian et al[14], 2010	China	June 2003 to June 2008	56	55	51.43 ± 7.01	52.87 ± 6.98	Kunbao Pill, Modified Xiaoyao Pill, and Psychological Intervention	Psychological Intervention	6 months	(8) (9) (11) (12)
Chen et al[15], 2003	China	-	24	14	50.17 ± 3.41	52.14 ± 5.33	Modified Xiaoyao Powder	Premelle	16 weeks	(8) (9) (10) (11)
Xu et al[16], 2021	China	February 2019 to February 2020	60	60	54.21 ± 2.12	54.23 ± 2.24	Conventional Western medicine treatment and Chaihu-Guizhi-Longgu-Muli decoction	Conventional Western medicine treatment and Liuwei Dihuang Pill	3 months	(5) (6) (8)
Ushiroyama et al[17], 2005	China	Not referred to	42	48	52.6 ± 5.7	53.1 ± 4.8	Chai-hu-gui-zhi-gan-jiang-tang	Antidepressant drug treatment	3-6 months	(1) (10)
Cao et al[18], 2019	China	August 2015 to June 2017	156	151	50.5 ± 4.8	50.8 ± 5.1	Psychological treatment and Bushen Tiaogan formula	Psychological treatment and placebo	8 weeks	(3) (4) (8) (9) (10) (11)
Zhang et al[19], 2020	China	January 2016 to March 2018	66	32	52.87 ± 2.99	52.67 ± 2.69	Improved Gengnianchun Formula (I-GNC)	Placebo	12 weeks	(1) (2) (9)
Wang et al[20], 2023	China	October 2016 to November 2017	31	32	49.71 ± 4.29	50.45 ± 4.70	Acupuncture and Bushen Tiaogan Formula	Acupuncture and placebo	8 weeks	(3) (4) (10)
Pei et al[21], 2023	China	September 2021 to September 2022	45	41	55.53 ± 5.82	55.63 ± 6.28	Xiangshao granules and Acupuncture	Acupuncture	8 weeks	(7)
Zhou et al[22], 2021	China	July 2018 to April 2020	51	51	49.62 ± 4.83	49.41 ± 4.72	Livumin tablets and Shugan Bushen Huoxue decoction	Livumin tablets and Gynecological Nourishing Capsule	12 weeks	(3) (4) (8) (9)
Xie et al[23], 2024	China	December 2021 to June 2023	165	162	51.1 ± 4.79	50.9 ± 4.70	Xiangshao granules	Placebo	8 weeks	(3) (4) (11)

T: Treatment; C: Control. (1): Hamilton Depression Rating Scale score; (2): Hamilton Anxiety Rating Scale score; (3): Self-Rating Depression Scale score; (4): Self-Rating Anxiety Scale score; (5): Hospital Anxiety and Depression Scale-Anxiety subscale score; (6): Hospital Anxiety and Depression Scale-Depression subscale score; (7): Patient Health Questionnaire-9 score; (8): Serum estrogen (E2): Level; (9): Follicle-stimulating hormone level; (10): Greene Climacteric Scale score; (11): Adverse events or side effects; (12): Kupermann Anxiety Scale score.

Table 3 Ingredients of liver-soothing Chinese herbal medicines included in the studies

Ref.	Liver-soothing	Liver-soothing formulas	Preparation	Dose	Frequency (times/day)
Chen et al[12], 2021	Xiangshao granules	Xiangfu (Cyperi Rhizoma), Baishao (Paeoniae Radix Alba), Chaihu (Bupleuri Radix), Chuanxiong (Chuanxiong Rhizoma), and Chuanlianziv (Toosendan Fructus)	Granules	4 g	3
Du et al[13], 2014	Xiaoyao pill	Chaihu (Bupleuri Radix), danggui (Angelicae Sinensis Radix), baishao (Paeoniae Radix Alba), chaobaizhu (Atractylodes Macrocephala), fuling (Poria), zhigancao (Glycyrrhizae Radix Et Rhizoma), Bohe (Menthae Haplocalycis Herba), and Shengjiang (Zingiberis Rhizoma Recens)	Pill	3 g	2
Qian et al[14], 2010	Modified Xiaoyao Pill	Chaihu (Bupleuri Radix), Danggui (Angelicae Sinensis Radix), Baishao (Paeoniae Radix Alba), Baizhu (Atractylodes Macrocephala), fuling (Poria), Gancao (Glycyrrhizae Radix Et Rhizoma), Mudanpi (Moutan Cortex), Zhizi (Gardeniae Fructus), and Bohe (Menthae Haplocalycis Herba)	Pill	6 g	2
Chen et al[15], 2003	Modified Xiaoyao Powder	Dangguigen (Angelicae Sinensis Radix), cangshu (Atractylodis Rhizoma), baishao (Paeoniae Radix Alba), Chaihu (Bupleuri Radix), fuling (Poria), Gancao (Glycyrrhizae Radix Et Rhizoma), Mudanpi (Moutan Cortex), Zhizi (Gardeniae Fructus), Shengjiang (Zingiberis Rhizoma Recens), and Bohe (Menthae Haplocalycis Herba)	Granules	4 g	3
Xu et al[16], 2021	Chaihu Guizhi Longgu Muli decoction	Chaihu (Bupleuri Radix), Huangqin (Scutellariae Radix), Guizhi (Cinnamomi Ramulus), Dangshen (Codonopsis Radix), Renshen (Ginseng Radix Et Rhizoma), Yejiaoteng (Caulis Polygoni Multiflori ), Shenglonggu (raw keel), Shengmuli (raw oyster), fuling (Poria), Banxia (Pinellia), Dahuang (rhubarb), Suanzaoren (wild jujube seed), and Shengjiang (Zingiberis Rhizoma Recens)	Decoction	400 mL	2
Ushiroyama et al[17], 2005	Chai hu gui zhi gan jiang tang	Bupleurum root (chai hu, Bupleurum Root, saiko), sctellaria root (Huang qin, Scutellariae Radix, Oregon), richosanthe root (gua lou gen, Trichosanthis Radix, karokon), cinnamon bark (gui pi, Cinnamomi Cortex, keishi), oyster shell (mu li, Ostreae Testa, borei), glycyrrhiza root (gan cao, Glycyrrhizae Radix, kanzo), and dried ginger rhizome (gan jian, Zingiberis Siccatum Rhizoma, kankyo)	Decoction	-	-
Cao et al[18], 2019	Bushen Tiaogan formula	Dihuang (Rehmanniae radix), Baishao (Paeoniae radix Alba), Chishao (Paeoniae radix Rubra), Yinyanghuo (Epimedium brevicornu Maxim), Duzhong (Eucommia ulmoides Oliver ), Yujin (Curcumae radix), Qianhu (Peucedani radix), and Baizhu (Atractylodis macrocephalae Rhizoma)	Granules	20 g	2
Zhang et al[19], 2020	Improved Gengnianchun Formula (I-GNC)	Shengdihuang (Rehmannia glutinosa Libosch), Xianlingpi (Epimedium brevicornu Maxim), Baishao (Paeoniae radix Alba), Xiangfu (Cyperi Rhizoma), Zhimu (Anemarrhena asphodeloides Bunge), Huangbai (Phellodendron chinense Schneid), Huanglian (Coptis chinensis Franch), and Fuling (Poria cocos (Schw.) Wolf)	Granules	11.6 g	1
Wang et al[20], 2023	Bushen Tiaogan Formula	Dihuang (Rehmanniae radix), Baishao (Paeoniae radix Alba), Chishao (Paeoniae radix Rubra), Yinyanghuo (Epimedium brevicornu Maxim), Duzhong (Eucommia ulmoides Oliver ), Yujin (Curcumae radix), Qianhu (Peucedani radix), and Baizhu (Atractylodis macrocephalae Rhizoma)	Granules	20 g	2
Pei et al[21], 2023	Xiangshao granules	Xiangfu (Cyperi Rhizoma), Baishao (Paeoniae Radix Alba), Chaihu (Bupleuri Radix), Chuanxiong (Chuanxiong Rhizoma), and Chuanlianziv (Toosendan Fructus)	Granules	4 g	3
Zhou et al[22], 2021	Shugan Bushen Huoxue Decoction	Shengdihuang (Rehmannia Glutinosa Libosch), Shudihuang (Rehmanniae Radix Praeparata), Gouqizi (Lycii Fructus), Shanyuzhu (Cornifructus), Shashen (AdeinophorastrictaMiq), Maidong (Ophiopogon japonicus (Linn.f.) Ker-Gawl.), Danggui (Angelicae Sinensis Radix), Chuanlianzi (Toosendan Fructus), Beichaihu (Bupleurum chinense DC), Baishao (Paeoniae Radix Alba), Danshen (Salviae Miltiorrhizae Radix Et Rhizoma), Yujin (Curcumae Radix), Chuanxiong (Chuanxiong Rhizoma), Xiangfu (Cyperi Rhizoma), Fuxiaomai (Fructus Tritici Levis), Gancaopian (Glycyrrhizae Radix Et Rhizoma), and Dazao (Jujubae Fructus)	Decoction	One dose per day, decocting it twice with regular water	2
Xie et al[23], 2024	Xiangshao granules	Xiangfu (Cyperi Rhizoma), Baishao (Paeoniae Radix Alba), Chaihu (Bupleuri Radix), Chuanxiong (Chuanxiong Rhizoma), and Chuanlianziv (Toosendan Fructus)	Granules	4 g	3