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Introduction
Sleep is a natural daily routine of mind and body.1 Accordingly, the sleep disturbance can followed by adverse health problems, such as impaired daytime function, fatigue, reduced quality of life and high healthcare utilization. Additionally, insomnia as a key risk factor accounts for major depression disorder. Aging is also an important contributor to high incidence of the sleep-induced concerns.2 One of the obvious symptoms appeared in menopause is sleep difficulty. Complaint of sleep disturbance can be seen among about 24% to 50% of the menopausal women while 15% of the general population.3
There are some approaches, including hormone therapy (HT), behavioral therapy, circadian rhythm training and medications and herbal medicine for the management of insomnia. 4
Cognitive behavioral therapy (CBT) can employ alongside other treatments. According to previous clinical trials, the CBT is equally or more effective compared to the pharmacological therapies. Antidepressants such as trazodone and nefazodone has therapeutic application for insomnia, especially insomnia caused by depression.4 Some of medications to treat the insomnia include benzodiazepine hypnotics like flurazepam and triazolam and non benzodiazipine hypnotics like zolpidem and zopiclone.5 Nevertheless, certain complications make them to be recruited in managing the acute sleep problems along with some other interventions such as behavioral therapy, circadian rhythm training and lifestyle modification. Many investigations reported the active and significant impacts of the HT on reducing the sleep disturbance.4
Regarding healthcare concerns on HT-induced tumors as well as positive attitudes toward medicinal plants especially phytoestrogens have attracted further attentions of many consumers to complementary and alternative medicine.6
Despite existing several systematic reviews and meta-analysis assessing the effect of herbal medicine on reducing the sleep problem, none of them has dealt with the menopause. Therefore, we decide to conduct the present systematic review and meta-analysis to examine the efficacy of herbal medicine on eliminating sleep problems in post- and perimenopausal women.
Materials and Methods
1. Objective
The aim of this systematic review was to assess the effect of herbal medicine on the sleep disorders.
2. Inclusion criteria
The current systematic review was conducted on published randomized controlled trials that met the following inclusion criteria: 1) including peri- and postmenopausal women; 2) being designed as parallel or crossover groups; 3) reporting at least different kinds of sleep problems; and 4) administering herbal medicine; and 5) studies used placebo as control group.
3. Search strategy
Three databases including MEDLINE, Scopus and the Cochrane Library (Cochrane Central Register of Controlled Trials) from inception to March 2018 were searched to find those trials examining the effect of herbal medicines on reducing the sleep problem. In addition, the references listed in the articles were included into search to find further studies.
To this end, the search keywords were (sleep or insomnia) AND (complementary therapies or alternative treatments or evening primrose oil or Oenothera biennis or Hypericum perforatum or herbal treatments, herbs or St. John's wort or phytomedicine or racemosa rhizome or Salvia officinalis or Trigonella foenum- graecum or Avocado plus or Black cohosh or cimicifuga or Evening primrose oil or flaxseed or fenugreek or dong quai or Ginseng or red licorice or red clover, Vitex agnus-castus, kava, Piascledine or yam). The search was performed without any language restriction.
4. Data extraction
Both authors separately extracted data, involving name of authors, name of country, design of study, age, status of menopause, level of complaints, type of measurement tool, type of intervention, number of participant in intervention and placebo group, rate of drop out and major relevant finding (Table 1).
5. Assessment of study quality using Collaboration's tool for evaluating risk of bias
Two authors using Cochrane Collaboration's tool to study
risk of bias independently performed assessment of study
quality. This tool assessed seven risks of bias, including
random sequence generation, allocation concealment, blinding
of participants and personnel, blinding of outcome assessment,
incomplete outcome data, selective reporting and
other sources of bias (Table 2).
6. Statistical analyses
Standardized mean difference (SMD) was chosen to pool the result from different trials. The Fixed effect model was applied because the result was homogeneous. The Cochrane Q and I2 index were performed to evaluate the heterogeneity. All of mentioned analyses were done using comprehensive Meta-analysis Version 2 (Biostat Inc., Englewood, NJ, USA).
Results
The processes of selecting articles for the systematic review are displayed in Figure 1. Overall, 12 randomized, placebo -controlled trials included to systematic review Characteristics of these trials showed in (Table 1).
1. Red clover
One trial compared the effect of red clover and placebo. Lipovac et al.7 in a crossover study (with a wash out period of 7 days) evaluated the effect of red clover-driven isoflavone on the sleep problems. Thus, 109 patients were randomized into 2 groups to receive red clover or placebo. The sleep dysfunctions were decreased significantly in the red clover group compared to the placebo group.
2. Fenugreek husk
A trial8 assessed the effect of fenugreek husk to manage the insomnia. In this study, 88 menopausal women were divided equally into 2 groups of fenugreek husk (n = 44) and placebo (44). Treatment with the fenugreek husk caused a statistically significant improvement (75%) in the insomnia in the intervention group as compared to the placebo group.
3. Soy
Six trials assessed the effect of soy on sleep problem. Two trials910 had suitable data for including to the meta-analysis. The SMD of sleep problem was lower in the soy group than in the placebo group (SMD = −0.996; P < 0.001; 95% confidence interval [CI], −1.42 to −0.563; 2 trials; fixed effect model; heterogeneity I2 = 0 %,P = 0.575; Fig. 2).
Four trials had inconsistent data to include in the meta-analysis. Therefore, we assessed them qualitatively. The first were performed by Liu et al.11 and compared 3 groups of soy, isoflavone and placebo. Comparison of 3 groups using analysis of covariance (ANCOVA) with baseline as covariate showed no significant difference in frequencies of insomnia among 3 groups (P = 0.199).
In second studies, Davinelli et al.12 compared soy containing equol and resveratrol with placebo. Percentage of women affected by sleep problems declined 37% (P < 0.001) at 1 month and 46% (P < 0.001) at months 6 in soy group. The grater improvement was observed in soy group regarding insomnia compared to placebo at 6 months but not at 1 month.
In third trials, Carmignani et al.13 studied 3 groups HT, placebo and soy. Comparison of 3 groups using one-way analysis of variance (ANOVA) indicated no statistical significant difference in the sleep problem among 3 groups (P = 0.42).
In last trials, Hanachi and Golkho14 randomized patients into one of 3 groups of soy milk pulse exercise, soy milk and placebo. Both soymilk plus exercise and soymilk groups were not different from placebo. However, pre- and postcomparisons were significant in both soymilk plus exercise and soy milk alone (P < 0.005). The improvement rate was 25% for soymilk plus exercise and 30% for soymilk alone. Authors reported no comparison between 2 intervention groups.
4. Bitter orange and lavender
One trial15 compared 3 groups of bitter orange, lavender and placebo. The mean difference of Pittsburgh Sleep Quality Index (PSQI) total score showed more prominent decrease in the lavender group (MD = −0.596; P = 0.003; 95% CI, −0.989 to −0.203; P = 0.003; 1 trial) and bitter orange (MD = −0.665; P = 0.001; 95% CI, −1.059 to −0.270; 1 trial) compared to placebo. The Same effect was observed between lavender and bitter orange group (MD = −0.220; P = 0263; 95% CI, −.606 to 0.165; 1 taril)
5. Valerian
Taavoni et al.16 compared the valerian and placeboon sleep disorder; 36% of women reported a significant improvement as comparison to only 8% in the placebo group, difference between group were significant.
6. Schisandra chinensis
One trial conducted by Park and Kim17. They compared the effect of Schisandra chinensis with placebo on insomnia symptoms. Repeated measurement ANOVA analysis showed that score of insomnia in patients receiving Schisandra chinensis was not different from patient receiving placebo (P = 0.188).
7. Pin bark extract
A trial was performed by Yang et al.18. They examined pin bark extract (Pycnogenol®) effect on sleep. Prominent improvement occurred in the Pycnogenol® group compared to the placebo at month 1, 3, and 6. All P values of less than 0.05 were considered to indicate statistical significance.
Discussion
This meta-analysis systematic review investigated the effect of medicinal plants on the management of insomnia. This review found 12 trials assessing the effect of herbal medicine on promoting the sleep disorders; including pin bark extract, Schisandra chinensis, valerian, the blend of lavender and bitter orange, fenugreek husk, soy and red clover.
Three trials91012 demonstrated a significant improvement after the administration of soy. Three trials1113 showed no significant improvement. Accordingly, it is difficult to reach definite conclusion based on these findings. According to a trial, there is of any significant beneficial effect of Schisandra chinensis. Evidence supported the impacts of red clover, the blend of lavender and bitter orange, pin bark extract in reducing the sleep disorders.
After the administration of 530 mg of valerian twice a day for one month, a statistically significant effect was observed on the quality of sleep in the menopausal women;16 whereas nightly dosing of valerian (valerian root extract of 100 mg) over 2 weeks failed to show significant result in elderly women.19 Since several weeks are required for many herbal agents to have positive impacts and that higher doses of valerian might be more effective,20 it is possible that discrepancy between 2 trials1619 may be related to higher dose and longer duration in the trial of Taavoni et al.16. A previous meta-analysis on the effect of valerian on the sleep problem in adult aged over 18 years found no more effective than the placebo,20 inconsistent with the study of Leach and Page20. The therapeutic response might be different between various age group due to varied etiologies of insomnia throughout the lifespan20. The valerian seems to be more beneficial in menopausal women with lower levels of estrogens. Therefore, larger trials are required to assess the effect of valerian on various subgroups (reproductive and menopausal women).
It should be noted that, there were some limitations in the current systematic review. Despite believing to comprehensive search, it is possible that we could not find some published respective trials. Many of trials included to this review had poor methodologic quality due to lack of intention to treat, insufficient randomization, and concealment and blinding. Therefore, there is a necessity for well-designed trials. As well, there is need for further studies with larger sample size to confirm the present findings. Any of these trials calculated post hoc analysis power. Hence, future trials are suggested to determine test power of findings. Few trials used the standardized tool, so future trials should assess the quality of sleep using reliable tool such as PSQI, Morning Sleep Questionnaire (MSQ) or sleep tested in laboratory using Polysomnography.
Conclusion
The present systematic review and meta-analysis found inadequate evidence to draw conclusion on recommendation or refuse the herbal medications especially soy. Findings about the positive effect of valerian, pin bark extract, fenugreek husk, lavender in combination with bitter orange and red clover should be introduced cautiously due to low number trials.
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