Efficacy of phytoestrogens for menopausal symptoms: a meta-analysis and systematic review

Figures & data

Figure 1 Flow diagram of study selection

Table 1 General characteristics of the 15 studies included in the meta-analysis. Age is presented as mean (standard deviation)

1st author, year of publication	Number of women	Inclusion criteria	Intervention (compound, daily dose)	Intervention period (months)	Age (years)
					Placebo	Phytoestrogen
Aso, 2012^Citation15	160	Postmenopausal	S-(-) equol, 5 mg	3	53.9 (3.4)	53.2 (3.6)
Atkinson, 2004^Citation16	205	Wolfe P2 or DY mammographic breast patterns	Isoflavones	12	55.2 (4.9)	55.1 (4.7)
Cancellieri, 2007^Citation17	142	Postmenopausal	Isoflavones, 72 mg	6	54.4 (4.2)	54.1 (5.2)
Del Giorno, 2010^Citation18	120	Postmenopausal	Trifolium, 40 mg	12	55.14 (4.97)	55.78 (4.93)
Ferrari, 2009^Citation19	180	Minimum of five moderate-to-severe hot flushes in last 7 days at baseline	Isoflavones, 80 mg	3	54.9 (4.6)	53.2 (4.3)
Han, 2002^Citation20	80	Menopause of at least 12 months	Isoflavones, 100 mg	4	49 (1.3)	48 (1.1)
Lewis, 2006^Citation11	99	Natural menopause with last menses 1–8 years before recruitment	Isoflavones, 42 mg	4	52.9 (3.6)	53.3 (3.1)
Nahas, 2007^Citation21	80	Postmenopausal	Isoflavones, 100 mg	10	56.2 (7.7)	55.1 (6.0)
Penotti, 2003^Citation22	62	Postmenopausal	Isoflavones, 36 mg	6	52.5 (2.3)	52.5 (2.5)
Petri Nahas, 2004^Citation23	50	Menopausal	Isoflavones, 60 mg	6	52.9 (5.11)	53.7 (5.45)
Riesco, 2011^Citation24	56	Postmenopausal	Isoflavones, 25 mg	6	58.3 (5.84)	60.1 (3.67)
Sammartino, 2006^Citation25	80	Postmenopausal	Isoflavones 60 mg; lignans 100 mg	3	50.6 (1.75)	50.9 (1.85)
Tice, 2003^Citation26	252	Menopausal; 45–60 years of age; experiencing at least 35 hot flushes per week	Isoflavones, 82 mg (Promensil); Isoflavones, 57 mg (Rimostil)	3	52.3 (3.4)	52.3 (2.9)
Van de Weijer, 2002^Citation27	30	Postmenopausal	Isoflavones, 82 mg	3	52.5 (5.2)	54.2 (7.4)
Van Patten, 2002^Citation28	157	Postmenopausal with breast cancer	Isoflavones, 90 mg	3	54.9 (6.5)	55.5 (6.3)

Table 2 Summary of Kupperman index and hot flush frequency reported in the studies included in the meta-analysis. Data are given as mean (standard deviation), except for side-effects which are reported as a number

	Number of women		Baseline KI		KI after intervention		Baseline hot flush frequency (/day)		Hot flush frequency after intervention (/day)		Side-effect number
Study	Placebo	Phyto	Placebo	Phyto	Placebo	Phyto	Placebo	Phyto	Placebo	Phyto	Placebo	Phyto
Aso^Citation15	60	66					2.9 (2.1)	3.2 (2.4)	1.9 (NA) change from baseline: −1.0 (2.0)	1.3 (NA) change from baseline: −1.9 (1.8)
Atkinson^Citation16	103	102					2.5 (3.0)	2.1 (2.7)	1.5 (2.0) change from baseline: −1.0 (1.8)	1.2 (2.3) change from baseline: −0.8 (2.1)
Cancellieri^Citation17	65	60	19.6 (8.5)	20.8 (9.1)	12.2 (7.2)	9.6 (5.7)
Del Giorno^Citation18	50	50	25.12 (9.02)	25.34 (10.17)	12.01 (9.01)	11.12 (8.68)
Ferrari^Citation19	94	82	23.5 (7.1)	23.4 (8.3)	16.1 (7.6)	17.5 (10.0)	7.5 (2.8)	8.0 (3.3)	5.3 (3.8)	4.7 (4.2)	8	6
Han^Citation20	40	40	40.3 (7.6)	44.6 (6.3)	41.6 (7.0)	24.9 (10.8)
Lewis^Citation11	33	33					4.72 (3.04)	4.08 (2.38)	3.79 (3.00)	3.37 (2.55)
Nahas^Citation21	38	38					10.1 (4.9)	9.6 (3.9)	5.9 (4.3)	3.1 (2.3)	4	7
Penotti^Citation22	34	28					8.6 (2.9)	9.9 (4.5)	4.0 (3.9)	4.6 (3.8)
Petri Nahas^Citation23	25	26	20.05 (6.14)	21.10 (6.11)	13.5 (5.0)	12 (6.0)	6.4 (2.4)	7 (1.8)	5.2 (2.8)	3.0 (2.1)	2	7
Riesco^Citation24	21	19	17.0 (9.35)	13.3 (9.9)	15.7 (9.0)	12.3 (9.56)
Sammartino^Citation25	36	39	31 (2.5)*	31 (3)*	26 (1.5)*	8 (1)*
Tice^Citation26	85	167					7.8 (2.35)	8.3 (3.83)	5.0 (3.76)	5.25 (4.17)	33	59
van de Weijer^Citation27	14	16					5.75 (5)	5.43 (2.6)	6.04 (5.5)	3.35 (3)
Van Patten^Citation28	64	59					7.4 (6.4)	7.1 (4.3)	4.9 (3.9)	5.3 (4.1)	14	28

KI, Kupperman index; Phyto, phytoestrogen; NA, not available

*, Mean and standard deviation were estimated from median and range²⁹

Figure 2 Meta-analysis (a) with sensitivity evaluation (b) for change in Kupperman index between placebo and phytoestrogen groups (seven studies included). The random-effects approach was used due to significant heterogeneity (Q = 370.03, I² = 98.38, p < 0.001). CI, confidence interval

Figure 3 Meta-analysis (a) with sensitivity evaluation (b) for change of hot flush frequency between placebo and phytoestrogen groups (10 studies included). The random-effects approach was used due to significant heterogeneity (Q = 22.75, I² = 60.43, p = 0.007). CI, confidence interval

Figure 4 Meta-analysis (a) with sensitivity evaluation (b) for the likelihood of side-effects between the placebo and phytoestrogen groups (five studies included). The random-effects approach was used due to significant heterogeneity (Q = 10.15, I² = 60.60, p = 0.038). OR, odds ratio; CI, confidence interval

Figure 5 Evaluation of publication bias for (a) Kupperman index, (b) hot flush frequency, and (c) side-effects

Figure 6 Quality assessment

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