{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T08:30:45Z","timestamp":1768293045915,"version":"3.49.0"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T00:00:00Z","timestamp":1752105600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Menopausal syndrome is a general term for a series of physical and psychological symptoms that women experience during menopause and perimenopause, which can lead to the occurrence of a variety of diseases. Many ingredients in Kunxinning granules have been used clinically to treat menopausal syndrome. However, evidence for its effectiveness is lacking.<\/jats:p><\/jats:sec><jats:sec><jats:title>Purpose<\/jats:title><jats:p>To investigate the efficacy and safety of Kunxinning Granules in patients with menopausal syndrome and to fully verify its clinical application value. Study design: A multicenter, randomized, double-blinded, placebo-controlled trial.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Eligible participants from 9 hospitals were randomly assigned in a ratio of 3:1 to the experimental group (Kunxinning granules) and the placebo group (Kunxinning granules simulated agent) for 12\u00a0weeks. The primary efficacy outcome was the score reduction of the modified Kupperman index compared with the baseline. The secondary efficacy index is the disappearance rate of 13 single symptoms of the modified Kupperman index. The evaluation time points are baseline, 4\u00a0weeks, 8\u00a0weeks, 12\u00a0weeks and 4\u00a0weeks of drug withdrawal.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 475 patients (356 in experimental group and 119 in placebo groups) were included in the analysis. The modified Kupperman index of patients in the experimental group and placebo group were 28.81 \u00b1 6.81 and 27.61 \u00b1 7.38. The modified Kupperman index of the experimental group improved after 4 weeks of treatment (experimental group: 21.45 \u00b1 6.29, placebo group: 23.79 \u00b1 6.90, 97.5%CI: -3.68 to \u22120.99, <jats:italic>p<\/jats:italic> = 0.007) and 8 weeks (experimental group: 15.18 \u00b1 5.82, placebo group: 20.93 \u00b1 7.29, 97.5%CI: \u22127.05 to \u22124.45, <jats:italic>p<\/jats:italic> &amp;lt; 0.0001), 12 weeks (experimental group: 10.27 \u00b1 5.44, placebo group: 19.70 \u00b1 7.25, 97.5%CI: \u221210.68 to \u22128.19, <jats:italic>p<\/jats:italic> &amp;lt; 0.0001) and 4 weeks of drug withdrawal (experimental group: 10.27 \u00b1 5.44, placebo group: 19.70 \u00b1 7.25, 97.5%CI: \u221210.86 to \u22128.35, <jats:italic>p<\/jats:italic> &amp;lt; 0.0001) were significantly lower than placebo group. Moreover, the experimental group\u2019s modified Kupperman index reduction from baseline was better than that of the placebo group at 4\u00a0weeks, 8\u00a0weeks, 12\u00a0weeks of treatment and 4\u00a0weeks of drug withdrawal (<jats:italic>p<\/jats:italic> &amp;lt; 0.0001). Moreover, the experimental group had a good improvement effect on all 13 symptoms of the modified Kupperman index after 12\u00a0weeks of treatment. There were no significant differences in adverse events between the two groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Kunxinning granules are a promising treatment for menopausal syndrome which can effectively reduce patients\u2019 hot flashes and sweating, insomnia, irritability and urinary symptoms and improve their quality of life.<\/jats:p><\/jats:sec><jats:sec><jats:title>Clinical Trial Registration<\/jats:title><jats:p><jats:ext-link>http:\/\/www.chinadrugtrials.org.cn\/clinicaltrials.searchlist.dhtml<\/jats:ext-link>, identifier CTR20140289.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fphar.2025.1512110","type":"journal-article","created":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T05:30:29Z","timestamp":1752125429000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Efficacy and safety of Kunxinning granules in patients with menopausal syndrome: a multicenter, randomized, double-blinded, and placebo-controlled trial"],"prefix":"10.3389","volume":"16","author":[{"given":"Guirong","family":"Zhou","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danfei","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin","family":"Qian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dianrong","family":"Song","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Yan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guiping","family":"Wan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuping","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lili","family":"Hou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"He","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cong","family":"Qi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weian","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,7,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e7586","DOI":"10.7759\/cureus.7586","article-title":"The genitourinary syndrome of menopause: an overview of the recent data","volume":"12","author":"Angelou","year":"2020","journal-title":"Cureus"},{"key":"B2","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1016\/s0277-9536(00)00147-7","article-title":"Is there a menopausal syndrome? Menopausal status and symptoms across racial\/ethnic groups","volume":"52","author":"Avis","year":"2001","journal-title":"Soc. Sci. and Med."},{"key":"B3","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/j.maturitas.2007.04.009","article-title":"Efficacy and tolerability of a medicinal product containing an isopropanolic Black cohosh extract in Chinese women with menopausal symptoms: a randomized, double blind, parallel-controlled study versus tibolone","volume":"58","author":"Bai","year":"2007","journal-title":"Maturitas"},{"key":"B4","doi-asserted-by":"publisher","first-page":"2531","DOI":"10.3390\/nu13082531","article-title":"Effects of soy protein containing of isoflavones and isoflavones extract on plasma lipid profile in postmenopausal women as a potential prevention factor in cardiovascular diseases: systematic review and meta-analysis of randomized controlled trials","volume":"13","author":"Bara\u0144ska","year":"2021","journal-title":"Nutrients"},{"key":"B5","doi-asserted-by":"publisher","first-page":"3212","DOI":"10.3390\/ijms22063212","article-title":"Utilization of isoflavones in soybeans for women with menopausal syndrome: an overview","volume":"22","author":"Chen","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"B6","doi-asserted-by":"publisher","first-page":"26","DOI":"10.26689\/jcnr.v6i6.4345","article-title":"Clinical efficacy of Western medicine combined with Chinese medicine for pelvic inflammatory disease (Damp-Heat and stasis type)","volume":"6","author":"Chen","year":"2022","journal-title":"J. Clin. Nurs. Res."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1115","DOI":"10.1093\/humupd\/dmab026","article-title":"Hormone therapy in the postmenopausal years: considering benefits and risks in clinical practice","volume":"27","author":"Genazzani","year":"2021","journal-title":"Hum. Reprod. update"},{"key":"B8","article-title":"SAS\u00ae 9.4 ODS graphics","author":"Guide","year":"2012"},{"key":"B9","doi-asserted-by":"publisher","first-page":"5","DOI":"10.4103\/jmh.jmh_242_23","article-title":"Exploring the efficacy and safety of black cohosh (Cimicifuga racemosa) in menopausal symptom management","volume":"15","author":"Hedaoo","year":"2024","journal-title":"J. Mid-life Health"},{"key":"B10","first-page":"640","article-title":"Enrichment process of paeoniflorin from kunyining granules with macroreticular resin","volume":"27","author":"Jiancheng","year":"2005","journal-title":"Chin. Tradit. Pat. Med."},{"key":"B11","doi-asserted-by":"publisher","first-page":"751207","DOI":"10.3389\/fphar.2021.751207","article-title":"Comparison of herbal medicines used for women\u2019s menstruation diseases in different areas of the world","volume":"12","author":"Jiao","year":"2022","journal-title":"Front. Pharmacol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"65","DOI":"10.6118\/jmm.2015.21.2.65","article-title":"The recent review of the genitourinary syndrome of menopause","volume":"21","author":"Kim","year":"2015","journal-title":"J. menopausal Med."},{"key":"B13","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1093\/cdn\/nzac047.031","article-title":"Ameliorating effects of phytotherapy on body weight and serum lipid profiles in menopause-induced rat model","volume":"6","author":"Kim","year":"2022","journal-title":"Curr. Dev. Nutr."},{"key":"B14","doi-asserted-by":"publisher","first-page":"608","DOI":"10.1038\/s41574-022-00708-0","article-title":"The interplay between diabetes mellitus and menopause: clinical implications","volume":"18","author":"Lambrinoudaki","year":"2022","journal-title":"Nat. Rev. Endocrinol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1080\/13697137.2020.1851183","article-title":"Hormone replacement therapy\u2013where are we now?","volume":"24","author":"Langer","year":"2021","journal-title":"Climacteric"},{"key":"B16","doi-asserted-by":"publisher","first-page":"101073","DOI":"10.1016\/j.ctcp.2019.101073","article-title":"Herbal prescription for managing menopausal disorders: a practice survey in Korean medicine doctors","volume":"38","author":"Lee","year":"2020","journal-title":"Complementary Ther. Clin. Pract."},{"key":"B17","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1515\/chem-2019-0035","article-title":"Phytochemical screening and estrogenic activity of total glycosides of Cistanche deserticola","volume":"17","author":"Li","year":"2019","journal-title":"Open Chem."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1119352","DOI":"10.3389\/fpubh.2023.1119352","article-title":"Effect of multidisciplinary health education based on lifestyle medicine on menopausal syndrome and lifestyle behaviors of menopausal women: a clinical controlled study","volume":"11","author":"Li","year":"2023","journal-title":"Front. public health"},{"key":"B19","doi-asserted-by":"publisher","first-page":"1749","DOI":"10.1142\/s0192415x20500871","article-title":"Benefits of herbal medicine on bone mineral density in osteoporosis: a meta-analysis of randomized controlled trials","volume":"48","author":"Lin","year":"2020","journal-title":"Am. J. Chin. Med."},{"key":"B20","doi-asserted-by":"publisher","first-page":"101225","DOI":"10.1016\/j.smrv.2019.101225","article-title":"Role of menopause and hormone replacement therapy in sleep-disordered breathing","volume":"49","author":"Lindberg","year":"2020","journal-title":"Sleep. Med. Rev."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1205","DOI":"10.1001\/jamainternmed.2016.2761","article-title":"Diagnosis and management of menopause: the national institute of health and care excellence (NICE) guideline","volume":"176","author":"Lumsden","year":"2016","journal-title":"JAMA Intern. Med."},{"key":"B22","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1007\/s11010-020-03879-4","article-title":"Ovariectomized rodents as a menopausal metabolic syndrome model. A minireview","volume":"475","author":"Medina-Contreras","year":"2020","journal-title":"Mol. Cell. Biochem."},{"key":"B23","doi-asserted-by":"publisher","first-page":"278","DOI":"10.3390\/ph15030278","article-title":"Benefits of Black cohosh (Cimicifuga racemosa) for women health: an up-close and in-depth review","volume":"15","author":"Mohapatra","year":"2022","journal-title":"Pharmaceuticals"},{"key":"B24","doi-asserted-by":"publisher","first-page":"2728","DOI":"10.1002\/ptr.8172","article-title":"Phytotherapeutic approach for conquering menopausal syndrome and osteoporosis","volume":"38","author":"Mohapatra","year":"2024","journal-title":"Phytotherapy Res."},{"key":"B25","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/S2213-8587(21)00018-8","article-title":"Menopause transition: a golden age to prevent cardiovascular disease","volume":"9","author":"Nappi","year":"2021","journal-title":"Lancet Diabetes and Endocrinol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1177\/2053369119866341","article-title":"Therapies for the management of genitourinary syndrome of menopause","volume":"26","author":"Palacios","year":"2020","journal-title":"Post. Reprod. Health"},{"key":"B27","doi-asserted-by":"publisher","first-page":"121255","DOI":"10.1016\/j.lfs.2022.121255","article-title":"Drugs for the treatment of postmenopausal symptoms: hormonal and non-hormonal therapy","volume":"312","author":"Pan","year":"2023","journal-title":"Life Sci."},{"key":"B28","doi-asserted-by":"publisher","first-page":"421","DOI":"10.23736\/S2724-6507.22.03712-5","article-title":"Phytotherapic approach in menopause: light and darkness","volume":"47","author":"Pandozzi","year":"2022","journal-title":"Minerva Endocrinol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"113050","DOI":"10.1016\/j.indcrop.2020.113050","article-title":"Phenylethanoid and iridoid glycosides production in Rehmannia elata NE brown ex prein. in vitro shoot cultures and their biological activity","volume":"158","author":"Pi\u0105tczak","year":"2020","journal-title":"Industrial Crops Prod."},{"key":"B30","doi-asserted-by":"publisher","first-page":"100863","DOI":"10.1016\/j.hermed.2024.100863","article-title":"An overview of systematic reviews of medicinal plants and herbal formulations for the treatment of climacteric symptoms","volume":"45","author":"Portella","year":"2024","journal-title":"J. Herb. Med."},{"key":"B31","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1016\/j.ecl.2015.05.001","article-title":"Menopausal symptoms and their management","volume":"44","author":"Santoro","year":"2015","journal-title":"Endocrinol. Metabolism Clin."},{"key":"B32","doi-asserted-by":"publisher","first-page":"S72","DOI":"10.3329\/bjp.v11is1.26948","article-title":"Effects of Curculigo orchioides total glucosides in mouse perimenopause model of related organization and organs morphology","volume":"11","author":"Shan","year":"2016","journal-title":"||| Bangladesh J. Pharmacol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/j.fitote.2015.11.011","article-title":"Monoterpene derivatives with anti-allergic activity from red peony root, the root of Paeonia lactiflora","volume":"108","author":"Shi","year":"2016","journal-title":"Fitoterapia"},{"key":"B34","doi-asserted-by":"publisher","first-page":"1098","DOI":"10.1111\/jan.14304","article-title":"Efficacy of mind\u2013body therapies and exercise\u2010based interventions on menopausal\u2010related outcomes among Asian perimenopause women: a systematic review, meta\u2010analysis, and synthesis without a meta\u2010analysis","volume":"76","author":"Shorey","year":"2020","journal-title":"J. Adv. Nurs."},{"key":"B35","doi-asserted-by":"publisher","first-page":"223","DOI":"10.2147\/PPA.S42852","article-title":"Correlation between the modified kupperman index and the menopause rating scale in Chinese women","volume":"7","author":"Tao","year":"2013","journal-title":"Patient Prefer. adherence"},{"key":"B36","doi-asserted-by":"publisher","first-page":"104904","DOI":"10.1016\/j.neuint.2020.104904","article-title":"Estrogen receptors-\u03b2 and serotonin mediate the antidepressant-like effect of an aqueous extract of pomegranate in ovariectomized rats","volume":"142","author":"Vald\u00e9s-Sustaita","year":"2021","journal-title":"Neurochem. Int."},{"key":"B37","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.bpobgyn.2021.12.001","article-title":"Hormone replacement therapy\u2013current recommendations","volume":"81","author":"Vigneswaran","year":"2022","journal-title":"Best Pract. and Res. Clin. obstetrics and Gynaecol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1080\/13697137.2020.1832461","article-title":"The treatment of menopausal symptoms by traditional Chinese medicine in Asian countries","volume":"24","author":"Wang","year":"2021","journal-title":"Climacteric"},{"key":"B39","doi-asserted-by":"publisher","first-page":"3960834","DOI":"10.1155\/2022\/3960834","article-title":"The evaluation of xiaozeng qianggu tablets for treating postmenopausal osteoporosis via up-regulated autophagy","volume":"2022","author":"Wu","year":"2022","journal-title":"Evidence-Based Complementary Altern. Med."},{"key":"B40","first-page":"1107","article-title":"Effect of kunyining capsule on reproductive endocrine-immune functions in ovariectomized rats","volume":"31","author":"Yang","year":"2006","journal-title":"Zhongguo Zhong yao za zhi= Zhongguo Zhongyao Zazhi= China J. Chin. Materia Medica"},{"key":"B41","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1038\/s41386-020-00915-1","article-title":"Sex differences in dopamine release regulation in the striatum","volume":"46","author":"Zachry","year":"2021","journal-title":"Neuropsychopharmacology"},{"key":"B42","doi-asserted-by":"publisher","first-page":"2629","DOI":"10.2174\/0109298673258420230919103405","article-title":"The therapeutic effect of natural compounds on osteoporosis through ferroptosis","volume":"31","author":"Zhang","year":"2024","journal-title":"Curr. Med. Chem."},{"key":"B43","doi-asserted-by":"publisher","first-page":"571598","DOI":"10.3389\/fphar.2020.571598","article-title":"Selective estrogen receptor modulator-like activities of herba epimedii extract and its interactions with tamoxifen and raloxifene in bone cells and tissues","volume":"11","author":"Zhou","year":"2021","journal-title":"Front. Pharmacol."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2025.1512110\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T05:30:31Z","timestamp":1752125431000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2025.1512110\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,10]]},"references-count":43,"alternative-id":["10.3389\/fphar.2025.1512110"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2025.1512110","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,10]]},"article-number":"1512110"}}