ETM Experimental and Therapeutic Medicine 1792-0981 1792-1015 D.A. Spandidos ETM-29-6-12866 10.3892/etm.2025.12866 Articles Examining the effect of Kuntai capsule combined with HRT in the treatment of premature ovarian insufficiency: A systematic review and meta-analysis LinFengning LianJunyu WuLijing Department of Obstetrics and Gynecology, Fujian Provincial Maternity and Children's Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350000, P.R. China Correspondence to: Dr Fengning Lin, Department of Obstetrics and Gynecology, Fujian Provincial Maternity and Children's Hospital, Affiliated Hospital of Fujian Medical University, 18 Daoshan Road, Fuzhou, Fujian 350000, P.R. China linfengning@sohu.com 06 2025 09 04 2025 29 6 116 20 10 2024 28 02 2025 Copyright: © 2025 Lin et al. 2025 This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

While Chinese herbal medicines have been used to treat premature ovarian insufficiency (POI), their efficacy is currently unclear. The present study aimed to review and evaluate the efficacy of the Kuntai capsule combined with hormone replacement therapy (HRT) in treating POI. The China National Knowledge Infrastructure, WanFang, Chinese Biomedical Literature, PubMed, Embase and Cochrane Library databases were searched from the inception of the database to 25th October 2020, for studies comparing the therapeutic effect of Kuntai capsule combined with HRT vs. HRT alone in women with POI. The Cochrane Risk of Bias assessment tool was used to assess the quality of the studies, and the results were reported as weighted mean differences (MD) with 95% confidence intervals (CI). The present study included 10 trials involving 742 women with POI. When compared with HRT alone, HRT combined with Kuntai capsule significantly increased the number of antral follicles (AFC) (MD=0.88; 95% CI, 0.48-1.29; P<0.00001), anti-Müllerian hormone (AMH) levels (MD=0.24, 95% CI, 0.13 to 0.35, P<0.00001) and significantly improved peri-menopausal symptoms [MD=-2.26; 95% CI, -3.77-(-0.75); P=0.003]. The combined treatment regimen significantly decreased the levels of follicle-stimulating hormone [MD=-5.60; 95% CI, -7.98-(-3.22); P<0.00001] and luteinizing hormone [MD=-2.42; 95% CI, -3.40-(-1.44), P<0.00001] and significantly increased the level of estradiol (MD=13.94; 95% CI, 4.16-23.71; P<0.00001). Therefore, the Kuntai capsule combined with HRT could potentially be used as a supplementary therapy to alleviate menstrual disorders and peri-menopausal symptoms and improve serum sex hormone levels in women with POI. The observed increase in the number of AFC in patients with POI treated with the combined therapy was indicative of improved ovarian reserve function. Therefore, combining the Kuntai capsule and HRT had am improved curative effect for POI treatment compared with HRT alone. However, as the present study was limited by the quality of the included reports, additional high-quality studies with extensive sample sizes are required to verify the findings.

 Kuntai capsule premature ovarian insufficiency number of antral follicles Funding: The Fujian Provincial Health and Youth Research Projects Funding Scheme (grant no. 2019-1-13) and Startup Fund for scientific research Fujian Medical University (grant no. 2021QH1201) funded the present study. Introduction

Premature ovarian insufficiency (POI) is an ovarian dysfunction that mainly occurs in women aged <40 years (1) and is characterized by menstruation abnormalities, elevated levels of follicle-stimulating hormone (FSH) and fluctuating estrogen hormone levels (2). The final stage of POI, premature ovarian failure, is associated with different degrees of perimenopausal symptoms, such as mood changes, hot flashes and trouble sleeping (3,4). POI affects ~1% of women worldwide (3) and, if not treated, may cause several long-term health conditions, such as osteoporosis, cardiovascular disease, anxiety and depression (4,5).

Presently, a standard treatment for POI is estrogen/progesterone combination therapy. However, this hormone replacement therapy (HRT) is associated with increased health risks, including breast cancer, stroke and cardiovascular diseases (5). According to Traditional Chinese Medicine, ovarian reserve hypofunction and infertility are caused by various conditions, such as kidney malfunction. Therefore, in Traditional Chinese Medicine, ovarian reserve hypofunction and infertility can be treated with alternative therapies (6).

Previous research has demonstrated certain therapeutic effects of the Kuntai capsule on certain symptoms associated with POI, which are related to decreased hormone levels (7). The Kuntai capsule has been used as a Chinese patent medicine for low ovarian reserve. The capsule is based on Huanglian Ejiao decoction consisting of six Chinese medicines: Coptis, Ejiao, Rehmannia glutinosa, Scutellaria baicalensis Georgi, Poria cocos and white peony root, which has been previously reported to improve peri-menopausal and menopausal symptoms (8). A meta-analysis found that in patients with POI, HRT combined with the Kuntai capsule is associated with a higher number of basal antral follicles, an increased number of eggs and a reduced cycle cancellation rate (9). Another 1-year study reported that adding the Kuntai capsule to conventional HRT improved the pregnancy rate in patients with POI (10). However, this regimen was associated with some adverse reactions (10).

The present study aimed to critically analyze the existing randomized clinical trials (RCTs) on the efficiency of the Kuntai capsule for POI treatment and assess whether the Kuntai capsule combined with HRT was more effective compared with HRT alone. These results may provide an evidence-based evaluation of the Kuntai capsule's efficacy for the treatment of POI.

 Materials and methods <sec> <title>Data sources and search strategy

A systematic literature search of the China National Knowledge Infrastructure (https://www.cnki.net), WanFang (https://med.wanfangdata.com.cn/), Chinese Biomedical Literature PubMed (https://www.sinomed.ac.cn/index.jsp) (https://pubmed.ncbi.nlm.nih.gov), Embase (http://embase.com) and Cochrane Library databases (https://www.cochranelibrary.com/central/about-central) was performed from the inception of the databases to 25th October 2020. RCTs that reported using the Kuntai Capsule treatment for POI and were written in English or Chinese were included. The following keywords were used: ‘Kuntai capsule’ AND (‘premature ovarian insufficiency’ OR ‘decline in ovarian reserve’ OR ‘ovarian reserve dysfunction’ OR ‘low ovarian reserve’) AND ‘randomized controlled trial’. A total of two reviewers conducted the searches and both reviewers agreed on the selected studies to be included in the present manuscript. In case of differences in the selection of studies, a third author was contacted to resolve the issue.

 Inclusion and exclusion criteria

The inclusion criteria used were as follows: i) RCTs; ii) POI diagnosis based on The European Society of Human Reproduction and Embryology, Guideline Group on POI (2); iii) patients aged <40 years with amenorrhea or oligomenorrhea for ≥4 months and serum follicle-stimulating hormone (FSH) levels >25 IU/l on ≥2 separate measurements (>4 weeks apart); iv) studies that reported data on the control group of patients treated with HRT alone; and v) studies that reported on outcomes of serological indices, such as levels of serum anti-Müllerian hormone (AMH), FSH, luteinizing hormone (LH), estradiol (E2), antral follicle count (AFC), Kupperman score (11) and imaging indicators, such as ovarian volume, endometrial thickness and peak systolic velocity (PSV) of the ovarian artery.

The exclusion criteria were as follows: i) Repeated published literature; ii) studies written in languages other than Chinese and English; iii) a lack of access to the full text; and iv) retrospective, cohort and qualitative studies, case reports or series, experience summaries and non-human studies.

 Data extraction

The relevant data, including title, first author name, publication year, patient grouping, age, course of the disease, treatment, control group type, indicators such as AMH, AFC, Kupperman score, FSH, LH, E2, ovarian volume, endometrial thickness and PSV were independently collected by two authors.

 Risk of bias

The risk of bias in the included studies was assessed using the Cochrane Risk of Bias Tool (12).

 Statistical analysis

RevMan Manage (version 5.3; The Cochrane Collaboration) was used for the meta-analysis of each intervention pair (Kuntai capsule combined with HRT treatment vs. HRT alone). Treatment effectiveness was expressed as weighted mean differences (MDs) and 95% confidence intervals (CIs) for continuous outcomes. Heterogeneity was assessed using a χ2 test and I2 statistics. The random-effects model was used irrespective of the inter-study heterogeneity measured using the I2 statistic. The Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines were strictly followed (13), and the requirements for ethics approval and patient consent were waived since the study used previously published data.

 Results <sec> <title>Study selection and characteristics

Screening identified a total of 742 articles. Of these articles, 10 met the criteria for standard RCTs and were included after the layer-by-layer screening (14-23). The included studies reported data on 925 patients. Of these patients, 462 received the Kuntai capsule combined with HRT treatment and 463 were treated with HRT alone. HRT treatment protocols included fenmetone, cremon and estrogen and progesterone therapy. The A similar HRT protocol was used in both the study and control groups. All patients were treated for 3 months and the changes in outcome indices before and after the treatment were compared (Table I). The flowchart of the screening is shown in Fig. 1. The Cochrane Risk of Bias Tool assessment showed that all 10 studies described the method of random grouping but did not detail the blinding method and allocation concealment, which could have affected the quality of the research. All RCTs were identified as having a ‘high’ or ‘unclear’ risk of bias (Fig. 2).

 Serum gonadotrophin and estradiol hormone levels

All 10 studies reported data on sex hormone levels. The Kuntai capsule combined with HRT treatment was associated with significantly reduced levels of FSH [MD=-5.60; 95% CI, -7.98-(-3.22); P<0.00001; I2=97%] and LH [MD=-2.42; 95% CI, -3.40-(-1.44); P<0.00001; I2=94%] (Figs. 3 and 4). Moreover, the Kuntai capsule, in combination with HRT treatment, significantly increased E2 levels (MD=13.94; 95% CI, 4.16-23.71; P<0.00001; I2=96%) when compared with HRT only (Fig. 5).

 AMH levels

A total of six studies (14,15,18-21) assessed the AMH levels. The Kuntai capsule treatment led to significantly increased levels of AMH (MD=0.24; 95% CI, 0.13-0.35; P<0.00001; I2=92%) (Fig. 6).

 Number of AFCs

A total of five studies (14,15,19-21) assessed the numbers of AFC. The pooled results showed that the numbers of AFC were significantly greater in the combined treatment group compared with the HRT alone group (MD=0.88; 95% CI, 0.48-1.29; P<0.00001; I2=95%) (Fig. 7).

 Improvement in perimenopausal symptoms

A total of four studies (17,20,22,23) used the Kupperman index to evaluate the improvement in perimenopausal symptoms. The pooled results suggested that the Kuntai capsule combined with HRT significantly improved the perimenopausal symptoms in patients with POI [MD=-2.26; 95% CI, -3.77(-0.75); P=0.003; I2=67%] compared with the HRT regimen alone (Fig. 8).

 Effects on the ovaries and uterus

A total of two studies (20,22) assessed ovarian volume, three (20-22) assessed endometrial thickness and one study (15) assessed PSV. The pooled analysis indicated that ovarian volumes were comparable in both groups of patients (MD=0.03; 95% CI, -0.60-0.65; P=0.94; I2=0%) (Fig. 9). However, the Kuntai capsule combined with HRT significantly improved the endometrial thickness (MD=0.78; 95% CI, 0.26-1.31; P=0.004; I2 =47%) (Fig. 10) and PSV (MD=1.24; 95% CI, 0.76-1.72; P<0.00001) (Fig. 11) in patients with POI.

 Discussion

The present study showed that combining the Kuntai capsule and HRT treatment significantly improved AMH levels and the number of AFCs in patients with POI compared with those treated with HRT alone. Kuntai capsule treatment also significantly reduced perimenopausal symptoms, reduced FSH and LH serum levels and increased serum levels of E2. These results suggested that the Kuntai capsule and HRT combination had an improved curative effect on improving ovarian reserve function during POI treatment compared with monotherapy with HRT alone.

POI has a profound negative impact on the quality of life (24). While HRT can relieve symptoms and mitigate the impact of prolonged estrogen deficiency, it mimics the normal physiological and endocrinological status, with no evidence of improvement in ovarian function (2). Moreover, HRT increases various health risks, including the risk for breast cancer, stroke and cardiovascular diseases (5).

Several traditional medical therapies, such as acupuncture and Chinese medicine, have been reported as being effective for the treatment of POI. Pharmacological studies have reported that the Kuntai capsule inhibits the apoptosis of ovarian granulosa cells in mice with POI and improves the secretion of sex hormones, thereby improving impaired ovarian function (25). Results of an animal study showed that the Kuntai capsule activates the PI3K/AKT/mTOR signaling pathway to improve the ovarian reserve function of mice with POI and protect their fertility (26). The aforementioned studies demonstrated the potential clinical value of the Kuntai capsule for POI treatment (27). A previous systematic review reported the superior efficacy and safety of the Kuntai capsule combined with HRT for POI treatment compared to HRT alone and showed that the Kuntai capsule combined with HRT can regulate serum estrogen and progesterone levels and reduce the adverse effects of hormone application such as nausea, vomiting, abdominal distension, headache, dysmenorrhea, breast tenderness, vaginal spotting, premenstrual syndrome and abnormal hepatic function. (28). A double-blind, randomized, controlled clinical study by Chen et al (29) investigated the clinical effectiveness and safety of the Kuntai capsule on peri-menopausal symptoms in patients with endometriosis who undergo postoperative gonadotropin-releasing hormone agonist (GnRH-a) treatment. The study reported that the main reported side effects of the combined Kuntai capsule and GnRH-a treatment included vaginal bleeding or spotting and breast-distending pain and showed that this regimen was associated with a significantly lower incidence of adverse effects compared with the regimen of GnRH-a + tibolone, a selective tissue-estrogenic-activity regulator.

In agreement with previous reports, the present study confirmed that the combined regimen of the Kuntai capsule with HRT effectively reduced hot flushes and related symptoms, reduced FSH and LH serum levels and increased serum levels of E2. Ma et al (30) showed that the Kuntai capsule was more effective in reducing the levels of FSH and LH and increasing the level of E2 compared with HRT only in the treatment of patients with premature ovarian failure. The results of the present study further confirmed these observations.

Furthermore, the present study showed that the Kuntai capsule combined with HRT increased endometrial thickness and peak systolic velocity of the ovarian artery, which indicated improved uterine and ovarian condition. It could be suggested that such changes may manifest in potentially increased pregnancy rates (28). On the other hand, combined therapy did not significantly affect the ovarian volume, which is considered as a marker of ovarian reserve (3,4). Furthermore, a meta-analysis by Zhang et al (31) reported that the Kuntai capsule improved the ovulation and pregnancy rates of patients with ovulatory disorders who underwent assisted reproduction treatment.

Additionally, the present study demonstrated that the combined regimen of the Kuntai capsule and HRT significantly improved AMH levels and the number of basic antral follicles in patients with POI. A study by Lian and Jiang (32) showed that the Kuntai capsule increased the number of retrieved oocytes and improved the quality of oocytes and embryos in patients undergoing fertility treatments. The Kuntai capsule combined with routine HRT could potentially be used before ovulation induction to increase the number of oocytes and reduce the cycle cancellation rate. Future studies should focus on the potential value of the Kuntai capsule in reproductive medicine.

While there have been two previous meta-analyses (33,34) that provided evidence of the increased effectiveness of the Kuntai capsule combined with HRT vs. HRT alone in improving outcomes of POI, the present study was unique in that it used a more robust inclusion criteria to include high quality data. Firstly, only studies which diagnosed POI based on The European Society of Human Reproduction and Embryology, Guideline Group on POI were included (2). Additionally, studies with patients <40 years in age were selected, with amenorrhea or oligomenorrhea for ≥4 months and serum FSH >25 IU/l on at least two separate measurements (>4 weeks apart). This provided a more robust diagnosis of POI, thereby providing higher-quality evidence.

The present study had certain limitations. First, the ‘unclear’ risk of bias in most incorporated studies reduced the credibility of the conclusions. Therefore, RCTs that comply with the Consolidated Standards of Reporting Trials reporting system are required to confirm our observations (32). Second, all included studies were conducted in China and reported data exclusively on patients of Chinese origin, thus limiting the generalizability of these results. Further trials of Traditional Chinese Medicines must include diverse populations and regions to provide more accurate and reliable data. Third, only articles written in Chinese and English were included because of language restrictions. Fourth, none of the included studies reported data on adverse reactions caused by treatment with the Kuntai capsule, hence a separate meta-analysis for this could not be conducted. Finally, the present study was limited by the quality of the included literature. Additional higher-quality studies with extensive sample sizes are needed to verify these observations and provide evidence supporting the clinical use of the Kuntai capsule.

In summary, the Kuntai capsule combined with HRT treatment could alleviate menstrual disorders and peri-menopausal symptoms and reduce serum sex hormone levels in patients with POI. This treatment also significantly increased the number of antral follicles in patients with POI compared with HRT alone. However, the present study was limited by the quality of the literature included. Additional high-quality studies with extensive sample sizes are required to verify these findings. However, given the limited side-effects of Kuntai capsule and potential benefits demonstrated through the present meta-analysis, it may be considered as a future supplemental therapy in patients using HRT with POI.

 Acknowledgements

Not applicable.

 Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

 Authors' contributions

FL conceived and designed the study. FL, JL and LW collected the data, performed the literature search and analyzed the data. FL was involved in the writing of the manuscript. FL edited the manuscript. All authors have read and approved the final version of the manuscript. FL and JL confirm the authenticity of all the raw data.

 Ethics approval and consent to participate

Not applicable.

 Patient consent for publication

Not applicable.

 Competing interests

The authors declare that they have no competing interests.

 References MaclaranKPanayNCurrent concepts in premature ovarian insufficiencyWomens Health (Lond)1116918220152577629110.2217/whe.14.82 European Society for Human Reproduction and Embryology (ESHRE) Guideline Group on POIWebberLDaviesMAndersonRBartlettJBraatDCartwrightBCifkovaRde Muinck Keizer-SchramaSHogervorstEESHRE guideline: Management of women with premature ovarian insufficiencyHum Reprod3192693720162700888910.1093/humrep/dew027 SadrzadehSPainterRCvan KasterenYMBraatDDMLambalkCBPremature ovarian insufficiency and perinatal parameters: A retrospective case-control studyMaturitas96727620172804159810.1016/j.maturitas.2016.11.015 Podfigurna-StopaACzyzykAGrymowiczMSmolarczykRKatulskiKCzajkowskiKMeczekalskiBPremature ovarian insufficiency: The context of long-term effectsJ Endocrinol Invest3998399020162709167110.1007/s40618-016-0467-z SullivanSDSarrelPMNelsonLMHormone replacement therapy in young women with primary ovarian insufficiency and early menopauseFertil Steril1061588159920162791288910.1016/j.fertnstert.2016.09.046 ChiJZhangYObservations on the efficacy of auricular pressure therapy combined with kuntai capsule in the treatment of uterine fibroids combined with perimenopausal syndromeHainan Med J27303230342016 XuJSunJExperimental study on the effect of prevention and treatment of Kuntai capsule on osteoporosis in ovariectomized rats-CNKIMode J Inte Trad Chin West Med24287328752015 ZhuJWangXMeta-analysis of efficacy and safety of Kuntai capsule combined with hormone therapy in treatment of climacteric syndromeChin Arch Trad Chin58652021 ZhangBZhangLYangYSunXYangLWangLZhangXEfficacy of Kuntai capsule for treating ovarian reserve dysfunction: A meta-analysisChin J Reprod Contracep407507552020 XuLClinical effect analysis of dehydroepiandrosterone combined with Kuntai capsule in the treatment of infertility due to hypo-ovarian reserveMater Child Heal Care Chin35385138542020 CaoHLiHLinGLiXLiuSLiPCongCXuLThe clinical value of acupuncture for women with premature ovarian insufficiency: A systematic review and meta-analysis of randomized controlled trialsFront Endocrinol (Lausanne)15136157320243905506210.3389/fendo.2024.1361573 HigginsJPTAltmanDGGøtzschePCJüniPMoherDOxmanADSavovicJSchulzKFWeeksLSterneJAThe cochrane collaboration's tool for assessing risk of bias in randomised trialsBMJ343d592820112200821710.1136/bmj.d5928 MoherDLiberatiATetzlaffJAltmanDGPRISMA GroupPreferred reporting items for systematic reviews and meta-analyses: The PRISMA statementPLoS Med6e100009720091962107210.1371/journal.pmed.1000097 LuanSCuiQZhangYMaHClinical efficacy of Kuntai capsule in the treatment of premature ovarian failureChin Tradit Pat Med39131813202017 LiWAnLZhangGThe combined application of estradiol valerate-cproterone acetate and Kuntai capsule in poor ovarian responders of in vitro fertilizationJ Pract Obstet Gynecol306816852014 JiaXClinical effect of Kuntai capsule combined with estradiol tablet/estradiol didroxyprogesterone tablet in the treatment of infertility with low ovarian reserve functionPract Clin Med2042432019 WuSStudy on the value of Kuntai and HRT treating premature ovarian failurePract Gynecol Endocr61141192019 YuanHHuYEffect of Kuntai capsule combined with hormone replacement therapy on premature ovarian failureHubei J TCM4116182019 YuanHHuYClinical observation of climen combined with kuntai capsule in treatment of diminished ovarian reserveHubei J TCM40792018 Hong: Clinical study on treatment of premature ovarian insufficiency with integrated Chinese and western medicine (unpublished thesis). Hubei University of Traditional Chinese Medicine, 2018. HuYThe application of kuntai combined with femoston in patients with premature ovarian insufficiency complicated with infertilityChin Med Mod Distance Edu China161071092018 XiaoPMXuYYShiYHClinical efficacy of Climen combined with Kuntai capsule for premature ovarian failureChin J Gener Pract137747757872015 YaoYXiaMWangCWanDClinical observation of Kuntai capsule combined with climen in treatment of diminished ovarian reserve. In: Proceedings of the 13th National Conference on traditional Chinese Medicine and Gynecology, Guiyang, pp611-612, 2013. TorrealdaySKodamanPPalLPremature ovarian insufficiency-an update on recent advances in understanding and managementF1000Res6206920172922579410.12688/f1000research.11948.1 ZhangJFangLShiLLaiZLuZXiongJWuMLuoAWangSProtective effects and mechanisms investigation of Kuntai capsule on the ovarian function of a novel model with accelerated aging ovariesJ Ethnopharmacol19517318120172784526710.1016/j.jep.2016.11.014 ZhangHQinFLiuASunQWangQLiQLuSZhangDLuZKuntai capsule attenuates premature ovarian failure through the PI3K/AKT/mTOR pathwayJ Ethnopharmacol23911188520193100970610.1016/j.jep.2019.111885 ZhouXWangLPanWLiJClinical Observation on the treatment of premature ovarian failure with Kuntai capsule combined with hormoneJ New Chin Med4979812017 LiuWNguyenTNTran ThiTVZhouSCorrigendum to ‘Kuntai capsule plus hormone therapy vs hormone therapy alone in patients with premature ovarian failure: A systematic review and meta-analysis’Evid Based Complement Alternat Med2021573791420213360381710.1155/2021/5737914 ChenJMGaoHYDingYYuanXWangQLiQJiangGHEfficacy and safety investigation of Kuntai capsule for the add-back therapy of gonadotropin releasing hormone agonist administration to endometriosis patients: A randomized, double-blind, blank- and tibolone-controlled studyChin Med J (Engl)12842743220152567344010.4103/0366-6999.151057 MaQTanYMoGEffectiveness of cotreatment with Kuntai capsule and climen for premature ovarian failure: A meta-analysisEvid Based Complement Alternat Med2020436735920203221503810.1155/2020/4367359 ZhangXZhangLXiongLLiuXZhangJYuFLiYChangWChenWKuntai capsule for the treatment of diminished ovarian reserve: A systematic review and meta-analysis of randomized controlled trialsJ Ethnopharmacol32911816720243859396410.1016/j.jep.2024.118167 LianFJiangXYEffect of kuntai capsule on the number of retrieved oocytes, high-quality oocytes and embryos in in vitro fertilization of poor ovarian response patientsZhongguo Zhong Xi Yi Jie He Za Zhi34917921201425223172(In Chinese) LiuWNguyenTNTran ThiTVZhouSKuntai capsule plus hormone therapy vs hormone therapy alone in patients with premature ovarian failure: A systematic review and meta-analysisEvid Based Complement Alternat Med2019208580420193134633710.1155/2019/2085804 LinWZengXPDengJLiuYCaiRHChenHYShiDHKuntai capsules in treatment of premature ovarian failure: A systematic review and meta-analysisJ Herb Med311005242022

Flow diagram of the study selection process demonstrating number of search results obtained from databases and number of studies screened to arrive to the final number of included studies.

Risk of bias assessment in included studies. Dotted line indicates the MD and SE of the pooled analysis. MD, mean difference.

Analysis of serum follicle-stimulating hormone levels before and after intervention. HRT, hormone replacement therapy.

Analysis of serum luteinizing hormone levels before and after intervention. HRT, hormone replacement therapy.

Analysis of serum estradiol levels before and after intervention. HRT, hormone replacement therapy.

Analysis of serum anti-Müllerian hormone levels before and after intervention. HRT, hormone replacement therapy.

Analysis of antral follicle count before and after intervention. HRT, hormone replacement therapy.

Analysis of Kupperman score before and after intervention.

Analysis of ovarian volume before and after intervention. HRT, hormone replacement therapy.

Analysis of endometrial thickness before and after intervention. HRT, hormone replacement therapy.

Analysis of peak systolic velocity before and after intervention. HRT, hormone replacement therapy.

Features of the included studies.

First author, year Cases (Kuntai + HRT group/HRT group), n Age, years (Kuntai + HRT group/HRT group; mean ± SD) Kuntai + HRT group drug regimen HRT group drug regimen Outcome measured (Refs.)
Luan et al, 2017 58/60 42.3±2.2/41.2±3.1 Kuntai capsule (2,000 mg three times daily) and fenmeton (one dose per day) Fenmetone (one dose per day) AMH, AFC and serum sex hormone levels (14)
Li et al, 2014 20/20 34.2±6.9/34.0±7.2 Kuntai capsule (2,000 mg three times daily) and cremon (one dose per day) Cremon (one dose per day) AMH, AFC and serum sex hormones levels and imaging examination (15)
Jia et al, 2019 46/46 30.2±2.1/30.4±2.1 Kuntai capsule (2,000 mg three times daily) and fenmetone (one dose per day) Fenmetone (one dose per day) Serum sex hormone levels (16)
Wu et al, 2019 50/50 35.0±3.3/34.6±3.5 Kuntai capsule (2,000 mg three times daily) and cremon (one dose per day) Cremon (one dose per day) Serum sex hormone levels and Kupperman score (17)
Yuan et al, 2019 40/40 34.2±2.8/34.1±3.0 Kuntai capsule (2,000 mg three times daily) and cremon (one dose per day) Cremon (one dose per day) AMH and serum sex hormone levels (18)
Yuan et al, 2018 40/40 35.2±2.6/35.8±2.1 Kuntai capsule (2,000 mg three times daily) and cremon (one dose per day) Cremon (one dose per day) AMH, AFC and serum sex hormone levels (19)
Hong et al, 2018 30/30 31.3±6.6/34.6±3.5 Kuntai capsule (2,000 mg three times daily) and cremon (one dose per day) Cremon (one dose per day) AMH, AFC and serum sex hormone levels, Kupperman score and imaging examination (20)
Hu et al, 2018 100/100 40.2±1.3/38.3±2.0 Kuntai capsule (2,000 mg three times daily) and fenmetone (one dose per day) Fenmetone (one dose per day) AMH, AFC and serum sex hormone levels and imaging examination (21)
Xiao et al, 2015 45/45 36.2±3.9/36.2±4.1 Kuntai capsule (2,000 mg three times daily) and cremon (one dose per day) Cremon (one dose per day) Serum sex hormone levels, Kupperman score and imaging examination (22)
Yao et al, 2013 33/32 32.5±3.4/31.4±3.7 Kuntai capsule (2,000 mg three times daily) and cremon (one dose per day) Cremon (one dose per day) Serum sex hormone levels and Kupperman score (23)

Femoston treatment is estradiol 2 mg and dydrogesterone 10 mg, cremon treatment is estradiol valerate 2 mg and estradiol cyproterone 10 mg. HRT, hormone replacement therapy.