Quality of life (QoL) for postmenopausal women has been a popular topic in the 21st century. Because of cessation of ovulation followed by sharp decrease in estradiol production and physiological changes, postmenopausal women may experience a degree of discomfort that is known as postmenopausal syndrome. Based on such manifestations, several scales have been developed to measure QoL for improving happiness and benefits for women after menopause. The contents of these scales generally include physical and psychological aspects. Complaints of physical problems may include hot flashes [
Phytoestrogen supplements are regarded as an alternative to hormone replacement therapy. This type of compound is derived mostly from plants and has structures resembling estrogen produced by the human endocrine system [
Although the consumption of phytoestrogen demonstrates physiological improvements, its effects on QoL for women after menopause remain unclear. Studies have conducted several randomized controlled trials (RCTs), but the outcomes have been inconsistent. Therefore, a more substantial and integrative result is required. The present study evaluated the effects of phytoestrogen supplements on QoL for postmenopausal women.
We conducted a systematic review and meta-analysis to assess the effect of phytoestrogen supplements on the QoL of postmenopausal women. Two researchers (Liu and Tung) searched PubMed, MEDLINE, Embase, and Cochrane Central Register of Controlled Trials from inception through March 31, 2018, for relevant publications. We did not impose any limitations on language. The search strategy is detailed in Table
Search strategy.
Database | Searching keywords |
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Cochrane library | (1) Postmenopause: 7873 |
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Medline | (1) exp postmenopause: 22329 |
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PubMed | (1) Postmenopause: 42081 |
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Embase | 'postmenopause'/exp AND ('phytoestrogen'/exp OR 'phytoestrogen' OR 'phytoestrogens' OR 'phytooestrogen' OR 'phytooestrogens' OR 'isoflavone derivative'/exp OR '5 hydroxy 7 prenyloxyisoflavone' OR '5 hydroxy 7, 4' dimethoxyisoflavone' OR 'isoflavone derivative' OR 'isoflavones' OR 'novasoy' OR 'novasoy 400' OR 'promensil' OR 'rimostil') AND 'quality of life'/exp; result=73 |
Included studies met the following inclusion criteria: the study design was an RCT, participants were human, experimental group received phytoestrogen supplements, and control group received a placebo. The titles and abstracts of all studies identified by our search were independently assessed by two of the authors for eligibility. These authors checked the full text of potentially eligible trials to determine whether they met the inclusion criteria. A third author arbitrated when the two authors disagreed on inclusion of a study.
Peng and Tung performed the data extraction and risk of bias assessment process. For all articles included, the following characteristics were obtained: first author, year, country, participants in the RCTs, characteristics of intervention, comparison groups, and outcome measurements. Because we expected different questionnaires or scales were utilized to determine QoL, we performed the meta-analyses based on the inquiry forms used.
The authors reviewed the titles and abstracts when searching the relevant studies after all references had been imported to EndNote. After a thorough appraisal of these publications, we indexed the full texts and subsequently assessed the risk of bias using the Cochrane Handbook for Systematic Reviews of Interventions [
A comprehensive screening was conducted to identify the questionnaires in the included trials. Among all studies, the Short Form 36 (SF-36) [
The SF-36 is a widely adopted scale worldwide for evaluating patients’ perception of their personal health status. It comprises the following sections to evaluate QoL: (1) vitality, (2) physical functioning, (3) body pain, (4) general health perceptions, (5) physical role functioning, (6) emotional role functioning, (7) social role functioning, and (8) mental health. These eight domains can also be categorized into two summary groups (physical and mental component summaries). After calculation according to the SF-36 Health Survey Manual and Interpretation Guide, raw scores were converted into a final scale from 0–100 that represented the overall QoL of the women.
The MENQOL is a QoL measurement introduced in 1996 and designed specifically for postmenopausal women. It is a Likert scale form that comprises 29 items that weigh the four domains of QoL for women after menopause: (1) vasomotor (items 1–3), (2) psychosocial (items 4–10), (3) physical (items 11–26), and (4) sexual (items 27–29) domains. Higher scores within a domain represent lower QoL in the respective aspect. The advantage of this widely used format is that it addresses the common postmenopausal symptoms [
We used Review Manager version 5.3.5 to calculate the overall effect of phytoestrogen supplements on QoL [
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses flowchart in Figure
Characteristics of included studies.
Author, year, country | Participants | Intervention | Comparison | Duration | Outcomes |
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Amato et al., 2012, U.S. | 403 postmenopausal women (120 mg/day group: n=134; 80 mg/day group: n=135; placebo group: n=134) | Aglycone soy isoflavone 80 mg; aglycone soy isoflavone 120 mg | Placebo contains cellulose | 2 years | MENQOL questionnaire |
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Attreitano et al. 2013, Italy | 262 postmenopausal women with diagnosed osteopenia | Genistein (n=139) | Identical appearance placebo (n=123) | 2 years | SF-36, ZSDS |
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Basaria et al. 2009, U.S. | 84 postmenopausal women (mostly Caucasian) | Genistein 64 mg, daidzein 63 mg, glycitein 34 mg (In the form of powder mixed with beverages) (n=38) | 20g of milk protein and other nutrients (same as experimental group) (n=46) | 12 weeks | MENQOL questionnaire |
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Garcia-Martin et al., 2012, Spain | 94 postmenopausal women | Soy isoflavone 50 mg/day (n=45) | Milk protein supplement (n=49) | 1 year | Cervantes Health-Related Quality of Life scale |
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Ho et al., 2007, China | 176 postmenopausal women with Chinese ethnicity that live in Hong Kong | 80 mg soy derived isoflavone per day (n=91) | Identical appearance placebo (starch) (n=85) | 6 months | SF-36, MMSE |
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Kok et al., 2005, U.S. | 202 postmenopausal women | 25.6 g soy protein (52 mg genistein, 41 mg daidzein, 6 mg glycitein) (n=100) | Milk protein (placebo) (n=102) | 1 year | SF-36, QLS, GDS scale |
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Lee et al., 2017, Korea | 84 postmenopausal women (n=84) | 336 mg soy extract (10.5% isoflavone) and various agents (n=41) | Dextrin instead of isoflavones (n=43) | 12 weeks | MENQOL questionnaire, Kupperman index |
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Lewis et al., 2006, Canada | 87 postmenopausal women | 25 g of flaxseed (50 mg lignans, n=28); 25 g of soy (42 mg of isoflavones) per day (n=31) | Wheat (for achieving similar fiber content) (n=28) | 16 weeks | MENQOL questionnaire, daily hot flash frequency estimation by a 7-point Likert scale |
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Riesco et al., 2011, Canada | 40 postmenopausal women | 4 phytoestrogen capsules per day (each contain 17.5 mg of isoflavones) (n=19) | Placebo contained cellulose (n=21) | 6 months | SF-36, Perceived stress scale, Kupperman index |
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Tice et al., 2003, U.S. | 246 menopausal women with hot flashes | Promensil (82 mg of isoflavones per day) (n=84); Rimostil (57 mg of isoflavone per day) (n=83) | Placebo (less than 0.04 mg isoflavones per tablet) (n=85) | 12 weeks | The change in frequency of hot flashes measured by participant daily diaries, Greene Climacteric Scale (QOL), adverse events |
PRISMA flow diagram.
We used the Cochrane Handbook for Systematic Reviews of Interventions to assess the risk of bias in the selected studies. The result is shown in Figure
Risk of bias for included studies.
We separately analyzed each domain of these two questionnaires and obtained a total of 12 outcomes (8 from the SF-36 [
Figures
(a) Meta-analysis result of SF-36 of physical function domain. (b) Meta-analysis result of SF-36 of role limitations caused by physical problems domain. (c) Meta-analysis result of SF-36 of pain domain. (d) Meta-analysis result of SF-36 of vitality domain. (e) Meta-analysis result of SF-36 of mental health domain. (f) Meta-analysis result of SF-36 of role limitations caused by emotional problems domain. (g) Meta-analysis result of SF-36 of social function domain. (h) Meta-analysis result of SF-36 of general health perception.
The MENQOL results are illustrated in Figures
(a) Meta-analysis result of MENQOL of vasomotor domain. (b) Meta-analysis result of MENQOL of physical domain. (c) Meta-analysis result of MENQOL of psychological domain. (d) Meta-analysis result of MENQOL of sexual domain.
Publication bias was defined as the publication or nonpublication of studies depending on the direction and statistical significance of the results and the first systematic investigations of publication bias focused on this aspect of the problem. As Figures
(a) Funnel plot based on SF-36 of physical function domain. (b) Funnel plot based on SF-36 of role limitations caused by physical. (c) Funnel plot based on SF-36 of pain domain. (d) Funnel plot based on SF-36 of vitality domain. (e) Funnel plot based on SF-36 of mental health domain. (f) Funnel plot based on SF-36 of role limitations caused by emotional problems domain. (g) Funnel plot based on SF-36 of social function domain. (h) Funnel plot based on SF-36 of general health perception. (i) Funnel plot based on MENQOL of vasomotor domain. (j) Funnel plot based on MENQOL of physical domain. (k) Funnel plot based on MENQOL of psychological domain. (l) Funnel plot based on MENQOL of sexual domain.
To our knowledge, this is the first meta-analysis of QoL related to the use of phytoestrogen supplements. The exact effect of phytoestrogen on QoL remains unclear. We performed a meta-analysis and acquired inconsistent results. We concluded several reasons for these results: type of questionnaire, difference between physical and mental conditions, and characteristics of involved patients.
Outcomes after meta-analysis were inconsistent; however, results did not confirm that these supplements improve QoL. The beneficial effects on biological functions have been proven by previous studies. Nevertheless, our research did not find a robust correlation between administration of supplements and enhancement of QoL.
Many of the included studies were conducted in Western countries. Indeed, postmenopausal life has been the subject of much research recently in Western countries. Although Asian women undoubtedly experience postmenopausal symptoms, certain aspects of postmenopausal syndrome, such as vasomotor symptoms, may be more common among Caucasian women [
There were several methodological limitations to this study. The major limitation was the number of available RCTs was insufficient; thus, the statistical power was low because of small study sample sizes. Another limitation to this study was the controversy surrounding random-effect models; that is, the assumption of normally distributed random effects violates the basic principle of randomization in statistical inference [
In conclusion, there is a lack of solid evidence supporting the routine use of phytoestrogen supplements for improving postmenopausal QoL. Future trials should employ an adequate sample size to provide data on various subgroups, for example, different age groups. Participants of various ethnic groups should be enrolled. Both efficacy and safety outcomes should be measured and reported. Additionally, trials that compare the effects of various durations of phytoestrogen supplementation are also required to determine the optimal duration of application. Trials including a third arm with no application at all (as in the present clinical practice) are warranted to estimate the placebo effect, which might affect interpretation of the effects of phytoestrogen supplements.
The data used to support the findings of this study are available from the corresponding author upon request.
The authors declare that they have no conflicts of interest.
Ching-Ching Peng designed and performed the study. Chia-Yu Liu, Nai-Rong Kuo and Tao-Hsin Tung analyzed the data and constructed the draft.
The authors appreciate the Sunflower Statistical Consulting Company, Kaohsiung, Taiwan, for statistical advice.