J Menopausal Med JMM Journal of Menopausal Medicine 2288-6478 2288-6761 The Korean Society of Menopause 10.6118/jmm.2018.24.1.11 Original Article Effect of Herbal Medicine on Vaginal Epithelial Cells: A Systematic Review and Meta-analysis Rahmani Yousef 1 Chaleh Khadijeh Chaleh 1 2 Shahmohammadi Afshar 1 Safari Shahla 1 Clinical Research Development Center, Imam Ali and Taleghani Hospital, Kermanshah University of Medical Sciences, Kermanshah, Iran. Department of Medical Surgical Nursing, Kermanshah University of Medical Science, Imam Reza Hospital, Kermanshah, Iran. Address for Correspondence: Shahla Safari, Clinical Research Development Center, Imam Ali and Taleghani Hospital, Kermanshah University of Medical Sciences, Shahidbehshti Boulevard, Kermanshah, Iran. Tel: +98-833-83959709, Fax: +98-833-8395970, Zehneziba_64@yahoo.com 04 2018 30 04 2018 24 1 11 16 24 08 2017 11 12 2017 26 12 2017 Copyright © 2018 by The Korean Society of Menopause 2018 The Korean Society of Menopause This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/). Objectives

The present meta-analysis aimed to assess the effect of the herbal medicine on the vaginal epithelial cells (VECs) among the menopausal subjects.

 Methods

The literature related to VECs exposed to various herbal medicines in menopausal women were searched on three databases, MEDLINE (1966–August 2017), Scopus (1990–August 2017) and Cochrane Library (Cochrane Central Register of Controlled Trials; 2014).

 Results

Totally, the meta-analysis was conducted on 11 randomised controlled trials. Based on the findings, the standardized mean difference (SMD) of maturation value (MV) was observed to be elevated by 0.48% (95% interval confidence [CI], 0.108–0.871; P = 0.012), as well as the heterogeneity was high (I2 = 84%; P < 0.001). The MV revealed a significant increase in soy group (SMD, 0.358; 95% CI, 0.073–0.871; P = 0.014) compared to the control group.

 Conclusions

The herbal medicines exhibited a statistically significant effect on the VECs. A significant effect on the VECs was also found in the subgroup analysis of the patients, who received soy. However, further and extensive studies are required to achieve reliable outcomes.

 Atrophic vaginitis Menopause Phytoestrogens Introduction

Menopause is a natural biological transition in life experienced by all women as they age,12 which is caused by end of ovarian function resulting in permanent discontinuation of the menstrual cycle.34 Women live a third of their life in the period of menopause.5

Some of the respective consequences following the menopause characterized by estrogen deficiency are vaginal atrophy, bone loss, mood and flashes.6 The quality of life of the postmenopausal women is affected by Genitourinary syndrome 7 whose symptoms though are attenuated widely by hormone therapy. Reportedly, there are several complications following the hormone therapy, including high risk of breast cancer, endometrial cancers,8 breast tenderness and venous thromboembolism.9 Therefore, the herbal medicines nowadays have attracted further attentions as safe alternatives by many postmenopausal women.10 To the best of our knowledge, limited studies investigated the effect of herbal medicine on vaginal atrophy among menopausal women and there are some new published trials. Accordingly, it is essential to update the knowledge through the systematic review or meta-analysis in this regard.

 Materials and Methods 1. Study design

The literature concerning the vaginal epithelial cells (VECs) exposed to various herbal medicines in menopausal women was searched on three databases of MEDLINE (1966–August 2017), Scopus (1990–August 2017) and Cochrane Library (Cochrane Central Register of Controlled Trials; 2014).

The keywords for searching were the relationship between menopause and primrose oil, St. John's wort, Hypericumperforatum, Black cohosh, Red clover, Piascledine, Avocado plus, Soy, kava, Cimicifuga racemosa rhizome, Licorice red, Trigonella foenum-graecum, Ginseng, fenugreek, Flaxseed, Dong quai, Vitex Agnus-Castus, Evening primrose oil, Yam, Salvia officinalis, alternative treatments, complementary treatments, Phytomedicine, herbal treatments or herbs.

The study inclusion criteria were the randomised controlled trials assessing oral herbal medicin effects on the maturation value (MV),11 which is measured following equation:10

MV= (% intermediate cells × 0.5) + (% superficial cells)

 2. Data extraction and quality assessment

Two reviewers independtly extracted the rerquired data among trials on the databases and the third reviwer was recruited to address the possible disagrements. The data included year of publication, first author, age of participants, rate of drop out, number of patients in the intervention and control groups. According to Physiotherrapy Eviedence Database (PEDro) scale, the two reviwers performed indepently the quality assessment of the trials.

 3. Statistical analysis

Comprehensive meta-analysis software12 was used to determine the standardized mean difference (SMD) for each study. The high heterogeneity among trials made us to reporte the data on the basis of Random Effect Model (Dersimonian and Laird method).

 Results

The selection process of randomized controlled trials (RCTs) for enrolling in the current meta-analysis is illustrated in Fig. 1, and the specifications of the studies have been summarized in Table 1. Overall, eleven studies1314151617181920212223 met our study inclusion criteria. The SMD of the of MV increased up to 0.48% (95% confidence interval [CI], 0.108–0.871; P = 0.012). The findings revealed high degree of heterogeneity (I2 = 84%; P < 0.001) (Fig. 2). Therefore, the sensitivity analysis was carried to explore the causes of heterogeneity in crossover trials. The individually exclusion of each study had no significant changes at the level of heterogeneity. No asymmetry was seen in the funnel plot of the trials assessing the effectiveness of herbal medicine on the of MV (Fig. 3). The absence of the publication bias was confirmed using the Egger's regression intercept test (P = 0.056) (Fig. 2). We also performed subgroup analysis for the women receiving soy. The of MV showed a significant increase by 0.358% (95% CI, 0.073–0.871; P = 0.014; I2 = 53%; P = 0.052) (Fig. 4).

 Discussion

This is the first meta-analysis to explore the herbal medicine effect on the VECs among menopausal women. According to our findings, the herbal medicine has had statistically significant effect on the vaginal atrophy.

The meta-analysis of several trials demonstrated that the SMD of the MV had significantly borderline increase in the soy group compared to the control group. However, heterogeneity was high. We performed the subgroup analysis in which the meta-analysis was limited to the trials evaluating the effectiveness of the soy on the VECs, which a significant increase was found in the effect size compared to previous meta-analyses. In addition, our meta-analysis had lower (I2 = 53%) homogeneity compared to the previous investigations (I2 = 81%).10

A systematic review assessed four trials on the effectiveness of administration of topical isoflavones on vaginal atrophy. The topical isoflavones had a beneficial effect on the vaginal atrophy. However, the authors concluded that there is a need to larger RCTs to confirm their results.24

In contrast to our meta-analysis that revealed a significant increase in the of MV, a systematic review and meta-analysis recently performed on the effectiveness of phytoestrogen on the of MV among menopausal women showed no significant improvement in phytoestrogen group compared to the control group 0.164% (CI, −0.419 to 0.746).25

Several limitations present in this meta-analysis included high heterogeneity, low number of trials, small sample size and methodological flaw, which are better to be addressed in the future studies. The high heterogeneity might be related to the variations and duration of treatment so that some trials did not report pre- and post-treatment means and standard deviations. In addition, no intention-to-treat has been reported in a larger portion of studies contained in the meta-analysis. The quality of trials can be improved due to further trials to follow the CONSORT guidelines.

 Conclusion

According to the findings obtained from our meta-analysis, the use of herbal medicines in different studies showed statistically significant positive effects on the VECs. The subgroup analysis of the patients receiving soy indicated also significant effects on the VECs. However, high heterogeneity among the trials makes ambiguous the definitive conclusions on the beneficial effects of herbal on the VECs.

No potential conflict of interest relevant to this article was reported.

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MV: maturation value. Effects of herbal medicine on vaginal epithelial cells (%). Horizontal line: 95% confidence interval (CI), █: point estimate, ♦: combined overall effect of treatment. Funnel plot of publication bias. Effects of soy on vaginal epithelial cells (%). Horizontal line: 95% confidence interval (CI), █: point estimate, ♦: combined overall effect of treatment. Characteristics of 11 randomized trials included in meta-analysis