Scholarly article on topic 'Effects of Korean herbal medicine on pregnancy outcomes of infertile women aged over 35: A retrospective study'

Effects of Korean herbal medicine on pregnancy outcomes of infertile women aged over 35: A retrospective study Academic research paper on "Clinical medicine"

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Abstract of research paper on Clinical medicine, author of scientific article — Sujeong Heo, Kwan-Il Kim, Junhee Lee, Eunjeong Jeong, Jaesung Lee

Abstract Introduction Delaying childbearing has led to an increased incidence of age-related female infertility. The interest in herbal medicine as an option for fertility care extends to many countries. The aim of this study was to evaluate the outcome of Korean herbal medicine treatment for women with infertility aged ≥35 years by calculating the clinical pregnancy and live birth rate through a retrospective analysis. Methods A retrospective analysis was carried out using computerized charts for 270 infertile women, over the age of 35 years receiving Korean herbal treatment from the Happysaem Korean Medicine Clinic, between 2011 and 2012. The main outcome measures were clinical pregnancy and live birth rates. Secondary outcome measures included the predictors of pregnancy success and treatment period/cost until pregnancy was achieved. Results Our results revealed that clinical pregnancy and live birth rates after Korean herbal treatment were 44.4% and 26.3%, respectively, in totality, 49.0% and 30.0%, respectively, in the 35–39 years group, and 31.4% and 15.7%, respectively, in the 40–46 years group. The clinical pregnancy rates were 44.0% in the Korean herbal treatment group and 43.4% in the Korean herbal treatment+western treatment group. The live birth rates were 23.5% in the Korean herbal treatment group and 31.3% in the Korean herbal treatment+western treatment group. The mean treatment duration was 11.26±5.02 weeks and average cost for Korean herbal treatment was $1320±600. Conclusions Our retrospective study suggests that management of infertile women ≥35 years with Korean herbal treatment can be effective and economical.

Academic research paper on topic "Effects of Korean herbal medicine on pregnancy outcomes of infertile women aged over 35: A retrospective study"

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European Journal of Integrative Medicine xxx (2016) xxx-xxx

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Contents lists available at ScienceDirect

European Journal of Integrative Medicine

journal homepage: www.elsevier.com/eujim

Research paper

Effects of Korean herbal medicine on pregnancy outcomes of infertile women aged over 35: A retrospective study

Sujeong Heoa, Kwan-Il Kimb,c, Junhee Leeb,c, Eunjeong Jeonga, Jaesung Leea'*

a Happysaem Korean Medicine Clinic, Nambusunhwanno 2563, Seocho-gu, Seoul 06734, Republic of Korea

b Department of Clinical Korean Medicine, College of Korean Medicine, Kyung Hee University, 23 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea

c Korean Medicine Clinical Trial Center, Kyung Hee University Korean Medicine Hospital, 23 Kyungheedae-ro, Dongdaemun-gu, Seoul, 02447, Republic of Korea

ARTICLE INFO

ABSTRACT

Article history:

Received 23 May 2016

Received in revised form 10 July 2016

Accepted 11 July 2016

Available online xxx

Keywords:

Korean herbal medicine Advanced maternal age Pregnancy outcome Female infertility Cost analysis Adverse events

Introduction: Delaying childbearing has led to an increased incidence of age-related female infertility. The interest in herbal medicine as an option for fertility care extends to many countries. The aim of this study was to evaluate the outcome of Korean herbal medicine treatment for women with infertility aged >35 years by calculating the clinical pregnancy and live birth rate through a retrospective analysis. Methods: A retrospective analysis was carried out using computerized charts for 270 infertile women, over the age of 35 years receiving Korean herbal treatment from the Happysaem Korean Medicine Clinic, between 2011 and 2012. The main outcome measures were clinical pregnancy and live birth rates. Secondary outcome measures included the predictors of pregnancy success and treatment period/cost until pregnancy was achieved.

Results: Our results revealed that clinical pregnancy and live birth rates after Korean herbal treatment were 44.4% and 26.3%, respectively, in totality, 49.0% and 30.0%, respectively, in the 35-39 years group, and 31.4% and 15.7%, respectively, in the 40-46 years group. The clinical pregnancy rates were 44.0% in the Korean herbal treatment group and 43.4% in the Korean herbal treatment + western treatment group. The live birth rates were 23.5% in the Korean herbal treatment group and 31.3% in the Korean herbal treatment + western treatment group. The mean treatment duration was 11.26 ± 5.02 weeks and average cost for Korean herbal treatment was $1320 ±600.

Conclusions: Our retrospective study suggests that management of infertile women >35 years with Korean herbal treatment can be effective and economical.

© 2016 The Authors. Published by Elsevier GmbH. This is an open access article under the CC BY-NC-ND

license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

1. Introduction

Today, women all over the world tend to delay childbearing due to postponement of marriage, professional pursuits, or educational achievements. The birth rate for women over the age of 35 years has risen continuously. It is reported that the birth rate for women >35 years has increased from approximately 35 births per 1000 women in 1990-61.5 in 2014 [1], and about 20% of women have their first child after the age of 35 in the USA [2]. These demographic shifts towards delayed childbearing may have led to the increase in age-related female infertility. According to a classic report on age-related infertility, the percentage of married

* Corresponding author. E-mail addresses: omqueen@naver.com (S. Heo), myhappy78@naver.com (K.-1. Kim), ssljh@daum.net (J. Lee), somangj00@naver.com (E. Jeong), eejsung@gmail.com (J. Lee).

women who remain childless increases progressively: 6% at age 20-24 years, 9% at age 25-29 years, 15% at age 30-34 years, 30% at age 35-39 years, and 64% at ages above 40 years [3]. Additionally, a prospective fecundability study has indicated that the infertility rate increases from 13 to 14% for women aged 27-34 to 18% for women aged 35-39 [4].

Most women who need fertility treatment are referred for costly conventional management with assisted reproductive technologies (ART) such as in vitro-fertilization (1VF). It is reported that the average cost of a single fresh 1VF cycle is $4950 (USD), ranging from $1800-$13,000 in 32 middle and high-income countries [5]. However, the success rates of ART start declining from the age of 35 years [6]. According to a large-scale research study, women aged 35-39 years and 40-44 years undertaking ART had only 24% and 11.2% probability, respectively, of conceiving, compared with 31.4% for women aged 30-34 years [7]. Therefore,

http://dx.doi.org/10.1016/j.eujim.2016.07.002

1876-3820/© 2016 The Authors. Published by Elsevier GmbH. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/

4.0/).

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ART could become a more serious financial burden for women with infertility aged 35 years and above.

Meanwhile, the use of traditional herbal medicine as an alternative for fertility care is becoming more widespread due to failure to conceive [8], and the efficacy of traditional herbal medicine is increasingly being recognized [9,10]. According to a systematic review, patients receiving herbal treatment had a 1.74 times higher probability of pregnancy compared with those receiving western medicine therapy [10]. Women aged >35 years are showing an interest in receiving herbal medicine treatment because of the low probability of success of ART. However, very few studies have investigated the effectiveness of herbal treatment in women with infertility aged >35 years.

Therefore, the aim of this study was to evaluate the outcome of Korean herbal medicine (KHM) treatment for women with infertility aged >35 years by calculating the clinical pregnancy and live birth rate through a retrospective analysis. In addition, we sought to investigate the predictors of pregnancy with KHM treatment. Medical costs per successful pregnancy were also evaluated.

2. Materials and methods

2.1. Subjects

The study participants were selected from among the 1332 patients who visited Happysaem Korean Medicine Clinic between January 1,2011 and December 31,2012 with the goal of conceiving. The inclusion criteria were as follows: women aged >35 years, KHM use of more than 4 weeks, no infertility factor in their male partner, and available follow-up information. Infertility was defined as the inability to conceive for six months or longer after having a normal married life [11]. All patients received KHM treatment from Happysaem Korean Medicine Clinic, although those who received combined western treatments (WT), including ovulation induction (OI), intrauterine insemination (IUI), or IVF at other institutes, were also included (Fig. 1). Finally, the charts of 270 patients were retrospectively evaluated for clinical pregnancy

rates (CPR), live birth rates (LBR), predictors of pregnancy success, and medical costs incurred during the treatment course.

2.2. Treatment

KHM refers to a decoction prescribed individually based on syndrome differentiation according to traditional Korean medicine theory. All patients were instructed to take herbal decoctions three times a day following a meal. Subject who received WT in addition to KHM, mainly used KHM for treatment preparation about 12 weeks before IVF or IUI, and in some cases were provided KHM following embryo transfer to support implantation and protect the fetus. The other combination was medication with ovulation-inducing agents such as clomiphene citrate in addition to KHM without undergoing IVF or IUI. Other traditional Korean medicine treatments such as acupuncture, moxibustion, or cupping were not used. The representative herbal prescriptions were Chokyungsoyo-san, Chokyungonshin-tang, and Guichulleekyung-tang. The herbal remedies we used and detailed compositions of prescriptions are shown in Appendix A.

2.3. Follow-up and assessment

Happysaem Korean Medicine Clinic follows the practice of performing follow-up visits and telephonic follow-up for patients receiving KHM treatment, to check on pregnancy and birth status. Accordingly, patients with verifiable follow-up between 6-12 months after the initial visit were included in the study.

Data related to baseline characteristics including age, duration of infertility, causes and type of infertility, previous ART experience, regularity of menstrual cycle length, and body mass index (BMI) were extracted. The main outcomes were CPR and LBR for the overall study population and for individual groups (KHM treatment only [KHM group] and KHM treatment combined with western treatment [KHM +WT group]). Data on the total medical costs (consultation fee and KHM costs) during the treatment course and the total treatment period was collected and adverse events examined.

Fig. 1. Flow chart of the analyzed patients.

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Clinical pregnancy was defined when a gestational sac was identified on ultrasound 5-7 weeks after KHM treatment, and live birth was defined as the birth of at least one live born infant of >20 weeks gestation. The birth of twins was considered as one live birth.

Causes of infertility were classified as being related to ovulation, structural factors related to the fallopian tubes and pelvis, uterus and cervix, ovaries, or an unexplained cause, based on the patient statements regarding previous western medical examinations. For cases in which western medical examination was not performed, the cause of infertility was classified as unknown (no examination).

This study was approved by the 1nstitutional Review Board of the Kyung Hee University Korean Medicine Hospital (approval number: K0MC1RB-150622-HR-020). Signed informed consent forms from participants were granted an exemption due to research design by the Institutional Review Board of the Kyung Hee University Korean Medicine Hospital.

2.4. Statistical analysis

Frequency analysis and descriptive statistics were performed to achieve a CI of 95%. For intergroup analyses, a chi-squared test was used for binomial analysis, while a t-test was used for continuous variables when the assumption of normality was satisfied. Otherwise, the Mann-Whitney U test was used. Predictors of clinical pregnancy were analyzed using a multivariate logistic regression model adjusted for covariates. All statistical analyses were performed using SPSS 18.0 (SPSS Inc., Chicago, 1L, USA). A p value of less than 0.05 was considered significant.

3. Results

3.1. Patient characteristics

A total of 270 women with infertility aged >35 years (range: 35-46 years), with an average infertility duration of 38.12 ± 30.07 months, were included in our analysis. Table 1 shows that the majority of causes of infertility were unexplained causes, endometriosis, or ovulatory dysfunction. The mean number of

previous ART treatments was 2.38 ±3.09 (range: 0-17), and the mean BM1 was 21.10 ± 2.58 kg/m2.

1n a comparison between the KHM and KHM + WT groups, significant differences were found in these characteristics: age (p = 0.021), obstetrical history (p = 0.021), and number of previous ART treatments (p <0.001).

3.2. Clinical pregnancy rates and live birth rates

As shown in Table 2, CPR and LBR for the overall study population were 44.4% and 26.3%, respectively. We divided patients into groups by age: 35-39 years and 40-46 years, because age >40 years is recognized as a more difficult age to conceive. We evaluated CPR and LBR in each group. The results showed that CPR and LBR were 49.0% and 30.0%, respectively in the 35-39 years group, and 31.4% and 15.7%, respectively, in the 40-46 years group. CPR was 44.0% in the KHM group and 43.4% in the KHM+WT group; LBR was 23.5% in the KHM group and 31.3% in the KHM+WT group. 1f 97 women who we could not contact 6-12 months post treatment were assumed to fail, CPR and LBR were 32.7% and 19.3%, respectively.

3.3. Predictors for pregnancy

After the univariate analysis, a multivariate logistic regression analysis was performed using backward stepwise only with variables for which the p value >0.2. We found that the predictors of pregnancy were age, duration of infertility, regularity of menstrual cycle length, and obstetrical history. Women aged 35 years or above were 15% less likely to achieve clinical pregnancy with a 1-year increase in age (odds ratio 0.85; 95% C1 0.76-0.94). The duration of infertility also affected the success of the treatment. A 1-year increase in the infertility period decreased the chances of pregnancy by 12% (odds ratio 0.88; 95% C1 0.790.98). Women with infertility with irregular menstrual cycles were 50% less likely to conceive compared to women with a regular menstrual cycle (odds ratio 0.50; 95% C1 0.25-0.98). Women with previous pregnancies had a 2-fold higher chance of conceiving than women who had never been pregnant before (odds ratio 2.09; 95% C1 1.24-3.52). Results are summarized in Table 3.

Table 1

Characteristics of the patients included in the study.

Total (n = 270) KHM (n = 166) KHM+WT (n = 99) P valuea

Age (y) 37.72 ±2.51 37.47 ±2.34 38.19 ±2.73 0.021

(35-46) (35-46) (35-44)

Duration of infertility (mo) 38.12 ±30.07 36.87 ± 29.8 40.64 ±30.69 0.155

(6-168) (6-134) (6-168)

Infertility diagnosis (%) 0.314

Ovulatory dysfunction 39 (14.4) 26 (15.7) 12 (12.1)

Tubal and pelvic factors 19 (7.0) 10(6.0) 9(9.1)

Endometriosis 47 (17.4) 29(17.5) 15 (15.2)

Ovarian factors 14 (5.2) 5 (3.0) 9(9.1)

Unexplained 132 (48.9) 79 (47.6) 52 (52.5)

Unknown cause 19 (7.0) 17(10.2) 2 (2.0)

Obstetrics history (%) 0.021

Primary infertility 115 (42.6) 60 (36.1) 53 (53.5)

Secondary infertility 155 (57.4) 106 (63.9) 46 (46.5)

Regularity of menstrual cycle length (%) 0.378

Regular 220 (81.5) 138 (83.1) 79 (78.8)

Irregular 50 (18.5) 28 (16.9) 21 (21.2)

Previous ART experience (n) 2.38 ±3.09 2.02 ±3.05 2.97 ± 3.08 <0.001

(0-17) (0-15) (0-17)

BMI(kg/m2) 21.10 ±2.58 21.16 ±2.55 20.96 ±2.55 0.572

(15-29) (15-29) (15-29)

KHM = Korean herbal medicine, WT = western treatment, ART = assisted reproductive technologies, BM1 = body mass index. ■"Univariate analysis, comparison between 'KHM' and 'KHM + WT'.

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Table 2

Pregnancy rates and live birth rates.

Pregnancies (n) Pregnancy rate (%) Deliveries (n) Live birth rate (%)

Total (n = 270) 120 44.4 71 26.3

35-39 (n = 200) 98 49.0 60 30.0

40-46 (n = 70) 22 31.4 11 15.7

KHM (n= 166) 73 44.0 39 23.5

35-39 (n= 133) 63 47.4 34 25.6

40-46 (n = 33) 10 30.3 5 15.2

KHM + WT (n = 99) 43 43.4 31 31.3

35-39 (n = 63) 32 50.8 25 39.7

40-46 (n = 36) 11 30.6 6 16.7

KHM = Korean herbal medicine, WT western treatment.

Table 3

Results of a multivariate logistic regression analysis of the predictors of pregnancy.

Univariate Multivariate

OR (95% CI) P value AOR (95% CI) P value

Age (y) 0.86 (0.77-0.95) 0.003 0.85 (0.76-0.94) 0.002

Duration of infertility (y) 0.88 (0.79-0.98) 0.015 0.88 (0.79-0.98) 0.017

Previous ART experience (n) 0.96(0.88-1.04) 0.281

BMI (kg/m2) 0.94 (0.85-1.04) 0.205

Type of treatment

KHM (ref) 1.00

KHM + WT 0.98 (0.59-1.62) 0.931

Regularity of menstrual cycle length

Regular (ref) 1.00 1.00

Irregular 0.59 (0.31-1.11) 0.102 0.50 (0.25-0.98) 0.045

Obstetrics history

Primary infertility (ref) 1.00 1.00

Secondary infertility 1.76 (1.08-2.89) 0.025 2.09 (1.24-3.52) 0.05

Infertility diagnosis

Unexplained (ref) 1.00

Ovulatory dysfunction 0.73 (0.35-1.51) 0.393

Tubal and pelvic factors 1.05 (0.40-2.75) 0.925

Endometriosis 0.94 (0.48-1.84) 0.856

Ovarian factors 0.65 (0.21-2.03) 0.456

Unknown cause 1.05 (0.40-2.75) 0.925

KHM = Korean herbal medicine, WT=western treatment, ART = assisted reproductive technologies, BMI = body mass index. OR = odds ratio, AOR=adjusted odds ratio.

3.4. Average treatment duration and medical cost of korean herbal therapy

The average treatment duration and KHM costs until conception are presented in Table 4. The mean treatment duration was 11.26 ±5.02 weeks and average medical cost was $1320 ±600.

3.5. Adverse events

During the treatment period, 15 patients out of the total 270 (5.6%) showed symptoms of diarrhea (7), mild abdominal pain (2), dyspepsia (2), sense of distension (2), nausea (1), and heartburn (1). However, there were no crucial adverse effects on patient health and all of these symptoms were temporary. There were no adverse effects on maternal, fetal, or neonatal health.

Table 4

Average treatment duration and cost in pregnancy group.

Total KHM KHM + WT

(n = 120) (n = 73) (n = 43)

Treatment duration (wk) 11.26 ± 5.02 10.90 ± 4.58 11.98 ± 5.70

Cost ($)a 1320 ± 600 1273 ± 554 1423 ± 665

KHM = Korean herbal medicine, WT=western treatment. a Mean cost: expenses incurred from KHM treatment alone.

4. Discussion

In the present study, the CPRand LBR of women aged >35 years with infertility were 44.4% and 26.3%, respectively, following KHM treatment. These results show higher success rates than a report of Korean IVF and ICSI outcomes in 2010 (23.2% CPR per retrieval in fresh cycle IVF in women aged over 35 years) [12]. The improved rate of success with KHM is still apparent if we assume that all of the 97 patients excluded due to unsuccessful follow-up failed to conceive. In these adjusted rates CPR and LBR were 32.7% and 19.3%, respectively.

There are several reports that pregnancy outcomes after ART in Asian women are lower compared with those in white women [1315]. On the contrary, our findings suggest that KHM may provide relatively better outcomes in treating women with infertility aged >35 years. Moreover, women above the age of 40 were found to have an overall CPR of 31.4% and LBR of 15.7% in our study, higher than that found in a retrospective review of IVF cycles in women 40 years and above, performed in Singapore (12.3% CPRand 6.7% LBR) [16]. Accordingly, it is possible that the effectiveness of herbal medicine on pregnancy, as verified by previous studies [10,17,18], may be generalized to women of advanced maternal age whose chances of a successful pregnancy are low.

Our observations about predictors of pregnancy outcome indicate that the possibility of conceiving declines with increasing age and duration of infertility among women aged 35 years and

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above. These findings confirm the existing knowledge about the effects of age [19,20] and duration of infertility [21,22] on pregnancy. Regularity of menstrual cycle length was also a predictor of pregnancy success, similar to reports by Kolstad et al. [23]. Additionally, results indicating that women with secondary infertility have a higher likelihood of becoming pregnant than those with primary infertility is in line with previous research [24]. 1n comparison, our logistic regression analysis revealed that cause of infertility, number of previous unsuccessful ART attempts, combined use of WT, and BM1 did not have an effect on pregnancy outcome. These results may be used as a basis for counseling patients >35 years old regarding KHM treatment for infertility.

From an economic perspective, the cost for KHM treatment for infertility care is relatively low ($1320 ±600, mean cost incurred for a successful pregnancy). 1t has been reported that the out of pocket costs for individual couples are up to USD 19,000 for the first 1VF cycle, and on average USD 7000 for additional cycles in the USA in 2011 [25]. According to the 2012 policy report, couples treated with 1VF spent an average of USD 2267 in Korea [26]. As the cost in the present study is the total payment for KHM until conception, KHM treatment may be more economical compared with 1VF.

The results from this study also show that no serious adverse events occurred during the treatment period. While 5.6% of patients exhibited mild symptoms, including diarrhea or mild abdominal pain, they soon recovered.

To our knowledge, this is the first retrospective study that evaluates pregnancy outcome including LBR and cost of KHM treatment for women with infertility over the age of 35. Although we attempted to minimize possible bias by including strict procedures, including strict enforcement of the inclusion criteria, our study does have some limitations. First, this is a retrospective study of the clinical records from a single institute. The records were based largely on patient statements, without objective examination values. Secondly, the relatively small number of subjects at a single center limits our ability to generalize the effectiveness and economics of KHM to other populations with infertility. Lastly, we enrolled patients whose charts had available follow-up results 6-12 months after the first visit. Hence, we could not avoid selection bias in spite of our best efforts. Thus, our results should be interpreted and applied with caution. Despite these limitations, the findings of this retrospective study suggest that KHM treatment might be beneficial in treating women with infertility over 35 years of age.

5. Conclusions

Our retrospective study suggests that the use of KHM for the management of women with infertility who are >35 years old can be effective and economical. Further investigations with well-designed and large randomized placebo-controlled trials are needed to confirm the efficacy of KHM in the treatment of women with infertility at advanced ages.

Conflict of interest

The authors declare that there is no conflict of interest regarding the publication of this paper.

Financial support

Author's contribution

Jaesung Lee designed the study and contributed to the editing of the paper. Sujeong Heo and Kwan-IL Kim contributed equally as first authors. All authors read and approved the final paper.

Acknowledgements

Appendix A.

Korean herbal medicine formulae

Compositions & dose (per day)

Frequency of usage (%)

Chokyunsoyo-san

Chokyungonshin-tang

Guichulleekyung-tang

Chokyungguibi-tang

Chokyung tonggyung-tang

Chokyungtonggyungsamul-tang

Bogibohyul-tang

Angelicae Gigantis Radix 8 g, Atractylodis Rhizoma Alba 8 g, Poria Sclerotium 8 g, Paeoniae Radix Alba 8 g, Liriopis seu Ophiopogonis Tuber 8 g, Bupleuri Radix 8 g, Moutan Radicis Cortex 8 g, Zingiberis Rhizoma Recens 6 g, Glycyrrhizae Radix et Rhizoma 4 g, Menthae Herba 4 g

Rehmanniae Radix Preparata 12 g, Corni Fructus 12 g, Morindae Radix 8 g, Cuscutae Semen 8 g, Angelicae Gigantis Radix 8 g, Eucommiae Cortex 8 g, Dioscoreae Rhizoma 8 g, Rehmanniae Radix 4 g, Alpiniae Oxyphyllae Fructus 4 g, Poria Sclertum cum Pini Radix 4 g, Polygalae Radix 4 g, Dipsaci Radix 4 g, Cnidi Fructus 4 g Persicae Semen 8 g, Moutan Radicis Cortex 8 g, Linderae Radix 8 g, Cinnamomi Cortex 6 g, Cyperi Rhizoma 8 g, Citri Unshius PericarpiumImmaturus 8 g, Sparganii Rhizoma 8 g, Rhizoma Zedoariae 8 g, Angelicae Gigantis Radix 8 g, Paeniae Radix Rubra 12 g, Corydalis Tuber 12 g, Sappan Lignum 8 g, Carthami Flos 4g Angelicae Gigantis Radix 8 g, Astragali Radix 8 g, Ginseng Radix

4 g, Poria Sclertum cum Pini Radix

8 g, Atractylodis Rhizoma Alba 8 g,

Longan Arillus 8 g, Zizyphi Semen 8 g, Polygalae Radix 4 g, Aucklandiae Radix 4 g, Glycyrrhizae Radix et Rhizoma 4 g, Zingiberis Rhizoma Recens 6 g, Zizyphi Fructus 4 g

Angelicae Gigantis Radix 8 g, Paeoniae Radix Alba 8 g, Rehmanniae Radix 8 g, Cnidii Rhizoma 8 g, Cistanchis Herba 8 g, Morindae Radix 8 g, Cinnamomi Cortex 6 g, Magnoliae Cortex 6 g, Mume Fructus 2 g, Cuscutae Semen

8 g, Lycii Fructus 8 g, Rubi Fructus 8 g, Salviae Miltiorrhizae Radix 6 g, Moutan Radicis Cortex 6 g, Ponciri FructusImmaturus 6 g, Sappan Lignum 6g, Carthami Flos 4g, Scutellariae Radix 6 g, Zingiberis Rhizoma Recens 6 g, Zizyphi Fructus 4g

Cyperi Rhizoma 16 g, Glycyrrhizae Radix et Rhizoma 4 g, Cinnamomi Cortex 4 g, Cnidii Rhizoma 8 g, Paeoniae Radix Alba 8 g, Sappan Lignum 6 g, Angelicae Gigantis Radix 12 g, Rehmanniae Radix Preparata 8 g, Rhizoma Zedoariae 6 g, Persicae Semen 4 g, Carthami Flos 3 g

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(Continued)

Korean herbal medicine Compositions & dose Frequency of

formulae (per day) usage (%)

Cnidii Rhizoma 8 g, Artemisiae Argyi Folium 8 g, Astragali Radix 8 g, Amomi Fructus 8 g, Asini Corii Colla 8 g, Atractylodis Rhizoma Alba 8 g, Cyperi Rhizoma 8 g, Citri Unshius PericarpiumImmaturus 8 g, Paeoniae Radix Alba 8 g, Ginseng Radix 4 g, Glycyrrhizae Radix et Rhizoma 8 g, Angelicae Gigantis Radix 8 g

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