Effectiveness and safety of Jiawei Xiaoyao pill (加味逍遥丸) in the treatment of premenstrual syndrome (liver depression, spleen deficiency, and blood-heat syndrome): a multi-center, randomized, placebo-controlled trial

doi:10.19852/j.cnki.jtcm.20231110.003

Abstract

Abstract:

OBJECTIVE: To investigate the effectiveness and safety of Jiawei Xiaoyao pill (加味逍遥丸，JXP) in the treatment of symptoms associated with premenstrual syndrome (PMS).

METHODS: A total of 144 regularly menstruating women with PMS were recruited at 8 sites in China from August 2017 to December 2018, and randomized to receive either a JXP or a matching placebo (12 g/d, 6 g twice a day) for 3 menstrual cycles. The primary indicator was the reduced Daily Record of Severity of Problems (DRSP) scores in the luteal phase after 3 months of treatment. The safety outcomes included clinical adverse events (AEs), adverse reactions (ARs), changes in vital signs, and laboratory tests.

RESULTS: JXP surpassed the placebo in reducing DRSP scores (psychological/somatic dysfunction) in the luteal phase over 3 menstrual cycles of treatment (PFAS = 0.002, PPPS = 0.001). Additionally, there were no significant differences in the incidence of AEs, severe AEs, withdrawal due to AEs and ARs between the two groups (all P > 0.05), and no clinically significant adverse medical events related to the test drug observed.

CONCLUSIONS: JXP was superior to the placebo in relieving the symptoms associated with PMS, which signified that JXP may be effective, safe, and well-tolerated as an alternative therapy.

Key words: premenstrual syndrome, randomized controlled trial, double-blind method, Jiawei Xiaoyao pill

LI Xiyu, YANG Yanhong, SUN Jian, NIE Quanfang, LIU Lifen, LI Guifen, YU Junping, ZHANG Zhuangjin, XU Yi, ZOU Ting, SHI Yun. Effectiveness and safety of Jiawei Xiaoyao pill (加味逍遥丸) in the treatment of premenstrual syndrome (liver depression, spleen deficiency, and blood-heat syndrome): a multi-center, randomized, placebo-controlled trial[J]. Journal of Traditional Chinese Medicine, 2024, 44(2): 373-380.

Figures/Tables 4

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Variable	JXP (n = 67)		Placebo (n = 69)		P value
Anthropometrics and occupation
Age (years)	29.47±5.58		29.22±6.11		0.800
Ethnic groups [n (%)]					1.000
Han	66 (98.51)		68 (98.55）
Others	1 (1.49)		1 (1.45）
Height (cm)	160.84±4.33		162.16±4.31		0.117
Weight (kg)	55.90±7.54		56.57±8.21		0.680
BMI (kg/m²)	21.61±2.81		21.48±2.70		0.901
Respiration (times/min)	18.27±1.34		18.06±1.33		0.411
Temperature (℃)	36.48±0.22		36.47±0.23		0.631
Pulse (times/min)	74.64±6.30		75.83±7.94		0.640
SBP (mm Hg)	107.85±9.62		108.41±9.26		0.935
DBP (mm Hg)	70.84±7.14		70.97±6.51		0.968
Occupation [n (%)]					0.713
Mental labour	55 (82.09)		60 (86.96)
Manual labour	4 (65.97)		3 (4.35)
Others	8 (11.94)		6 (8.70)
Medical history
Menstrual cycle (days)	28.24±2.26		28.57±2.12		0.513
Pregnancy history (times)	1.31±1.47		1.19±1.45		0.545
Labor history (times)	0.76±0.78		0.77±0.81		0.993
History of drug allergy [n (%)]					1.000
No	62 (92.54)		64 (92.75)
Yes	5 (7.46)		5 (7.25)
Previous treatment history of PMS [n (%)]					0.718
No	64 (95.52)		64 (92.75)
Yes	3 (4.48)		5 (7.25)
Outcome measures
Average scores of DRSP in the luteal phase	76.06±12.02		76.21±12.36		0.944
Average scores of DRSP in the follicular phase	43.01±11.92		42.93±10.37		0.776
DRSP scores in follicular and luteal phases-baseline
Change in average score	33.05±11.74		33.28±13.70		0.932
Rate of change (%)	88.75±53.90		88.83±59.16		0.884
Average scores of psychological/somatic symptoms of DRSP	69.23±9.68		69.59±10.10		0.830
Average scores of dysfunction of DRSP	6.83±2.96		6.61±3.02		0.676
TCMSSS [n (%)]
Breast tenderness/nipple pain					0.117
0	1 (1.49)		6 (8.70)
2	24 (35.82)		25 (36.23)
4	29 (43.28)		31 (44.93)
6	13 (19.40)		7 (10.14)
Costal pain					0.359
0	28 (41.79)		25 (36.23)
2	32 (47.76)		33 (47.83)
4	7 (10.45)		10 (14.49)
6	0 (0.00)		1 (1.45)
Anxiety and irritability					0.014^a
0	1 (1.49)		0 (0.00)
2	15 (22.39)		29 (42.03)
4	38 (56.72)		34 (49.28)
6	13 (19.40)		6 (8.70)
Depressive symptoms					0.665
0	8 (11.94)		13 (18.84)
2	39 (58.21)		35 (50.72)
4	20 (29.85)		20 (28.99)
6	0 (0.00)		1 (1.45)
Dizziness					0.607
0	12 (17.91)		13 (18.84)
2	39 (58.21)		43 (62.32)
4	16 (23.88)		12 (17.39)
6	0 (0.00)		1 (1.45)
Fatigue					0.579
0		0 (0.00)		1 (1.45)
2		32 (47.76)		36 (52.17)
4		33 (49.25)		28 (40.58)
6		2 (2.99)		4 (5.80)
Loss of appetite					0.950
0		35 (52.24)		34 (49.28)
2		20 (29.85)		27 (39.13)
4		12 (17.91)		8 (11.59)
6		0 (0.00)		0 (0.00)
Abdominal distension and pain					0.876
0		11 (16.42)		14 (20.29)
2		37 (55.22)		31 (44.93)
4		16 (23.88)		23 (33.33)
6		3 (4.48)		1 (1.45)
Bitter taste and dry throat					0.798
0		9 (13.43)		10 (14.49)
2		40 (59.70)		42 (60.87)
4		15 (22.39)		13 (18.84)
6		3 (4.48)		4 (5.80)
Menorrhagia/hypomenorrhea					0.484
0		29 (43.28)		34 (49.28)
1		38 (56.72)		35 (50.72)
Tongue texture					0.219
n (missing)		51 (16.00)		51 (18.00)
Red tongue [n (%)]		47 (92.6)		43 (84.31)
Others [n (%)]		4 (7.84)		8 (15.69)
Tongue coating					0.668
n (missing)		51 (16.00)		52 (17.00)
Yellow [n (%)]		41 (80.39)		40 (76.92)
Others [n (%)]		10 (19.61)		12 (23.08)
Pulse					0.241
n (missing)		43 (24.00)		43 (26.00)
Wiry and thin/slippery [n (%)]		43 (100.00)		40 (93.02)
Others [n (%)]		0 (0.00)		3 (6.98)

Variable	JXP (n = 67)		Placebo (n = 69)		P value
Anthropometrics and occupation
Age (years)	29.47±5.58		29.22±6.11		0.800
Ethnic groups [n (%)]					1.000
Han	66 (98.51)		68 (98.55）
Others	1 (1.49)		1 (1.45）
Height (cm)	160.84±4.33		162.16±4.31		0.117
Weight (kg)	55.90±7.54		56.57±8.21		0.680
BMI (kg/m²)	21.61±2.81		21.48±2.70		0.901
Respiration (times/min)	18.27±1.34		18.06±1.33		0.411
Temperature (℃)	36.48±0.22		36.47±0.23		0.631
Pulse (times/min)	74.64±6.30		75.83±7.94		0.640
SBP (mm Hg)	107.85±9.62		108.41±9.26		0.935
DBP (mm Hg)	70.84±7.14		70.97±6.51		0.968
Occupation [n (%)]					0.713
Mental labour	55 (82.09)		60 (86.96)
Manual labour	4 (65.97)		3 (4.35)
Others	8 (11.94)		6 (8.70)
Medical history
Menstrual cycle (days)	28.24±2.26		28.57±2.12		0.513
Pregnancy history (times)	1.31±1.47		1.19±1.45		0.545
Labor history (times)	0.76±0.78		0.77±0.81		0.993
History of drug allergy [n (%)]					1.000
No	62 (92.54)		64 (92.75)
Yes	5 (7.46)		5 (7.25)
Previous treatment history of PMS [n (%)]					0.718
No	64 (95.52)		64 (92.75)
Yes	3 (4.48)		5 (7.25)
Outcome measures
Average scores of DRSP in the luteal phase	76.06±12.02		76.21±12.36		0.944
Average scores of DRSP in the follicular phase	43.01±11.92		42.93±10.37		0.776
DRSP scores in follicular and luteal phases-baseline
Change in average score	33.05±11.74		33.28±13.70		0.932
Rate of change (%)	88.75±53.90		88.83±59.16		0.884
Average scores of psychological/somatic symptoms of DRSP	69.23±9.68		69.59±10.10		0.830
Average scores of dysfunction of DRSP	6.83±2.96		6.61±3.02		0.676
TCMSSS [n (%)]
Breast tenderness/nipple pain					0.117
0	1 (1.49)		6 (8.70)
2	24 (35.82)		25 (36.23)
4	29 (43.28)		31 (44.93)
6	13 (19.40)		7 (10.14)
Costal pain					0.359
0	28 (41.79)		25 (36.23)
2	32 (47.76)		33 (47.83)
4	7 (10.45)		10 (14.49)
6	0 (0.00)		1 (1.45)
Anxiety and irritability					0.014^a
0	1 (1.49)		0 (0.00)
2	15 (22.39)		29 (42.03)
4	38 (56.72)		34 (49.28)
6	13 (19.40)		6 (8.70)
Depressive symptoms					0.665
0	8 (11.94)		13 (18.84)
2	39 (58.21)		35 (50.72)
4	20 (29.85)		20 (28.99)
6	0 (0.00)		1 (1.45)
Dizziness					0.607
0	12 (17.91)		13 (18.84)
2	39 (58.21)		43 (62.32)
4	16 (23.88)		12 (17.39)
6	0 (0.00)		1 (1.45)
Fatigue					0.579
0		0 (0.00)		1 (1.45)
2		32 (47.76)		36 (52.17)
4		33 (49.25)		28 (40.58)
6		2 (2.99)		4 (5.80)
Loss of appetite					0.950
0		35 (52.24)		34 (49.28)
2		20 (29.85)		27 (39.13)
4		12 (17.91)		8 (11.59)
6		0 (0.00)		0 (0.00)
Abdominal distension and pain					0.876
0		11 (16.42)		14 (20.29)
2		37 (55.22)		31 (44.93)
4		16 (23.88)		23 (33.33)
6		3 (4.48)		1 (1.45)
Bitter taste and dry throat					0.798
0		9 (13.43)		10 (14.49)
2		40 (59.70)		42 (60.87)
4		15 (22.39)		13 (18.84)
6		3 (4.48)		4 (5.80)
Menorrhagia/hypomenorrhea					0.484
0		29 (43.28)		34 (49.28)
1		38 (56.72)		35 (50.72)
Tongue texture					0.219
n (missing)		51 (16.00)		51 (18.00)
Red tongue [n (%)]		47 (92.6)		43 (84.31)
Others [n (%)]		4 (7.84)		8 (15.69)
Tongue coating					0.668
n (missing)		51 (16.00)		52 (17.00)
Yellow [n (%)]		41 (80.39)		40 (76.92)
Others [n (%)]		10 (19.61)		12 (23.08)
Pulse					0.241
n (missing)		43 (24.00)		43 (26.00)
Wiry and thin/slippery [n (%)]		43 (100.00)		40 (93.02)
Others [n (%)]		0 (0.00)		3 (6.98)

Group	FAS				PPS
Group	n	Cycle 1	Cycle 2	Cycle 3	n	Cycle 1	Cycle 2	Cycle 3
JXP	67	19.5±16.7	26.2±17.0	32.8±15.5	61	18.6±16.4	25.7±16.8	33.0±15.3
Placebo	69	15.0±17.8	21.7±15.7	24.4±16.1	63	13.6±17.9	20.1±15.2	23.1±15.8
P value		0.129	0.109	0.002^a		0.105	0.054	0.001^a

Group	FAS				PPS
Group	n	Cycle 1	Cycle 2	Cycle 3	n	Cycle 1	Cycle 2	Cycle 3
JXP	67	19.5±16.7	26.2±17.0	32.8±15.5	61	18.6±16.4	25.7±16.8	33.0±15.3
Placebo	69	15.0±17.8	21.7±15.7	24.4±16.1	63	13.6±17.9	20.1±15.2	23.1±15.8
P value		0.129	0.109	0.002^a		0.105	0.054	0.001^a

Group	FAS				PPS
Group	n	Cycle 1	Cycle 2	Cycle 3	n	Cycle 1	Cycle 2	Cycle 3
JXP	67	17.91	47.76	70.15	61	18.03	47.54	68.85
Placebo	69	10.14	33.33	46.38	63	9.52	33.33	47.62
P value		0.192	0.087	0.005^a		0.168	0.107	0.017^a

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