Ding Xuesong, Tao Tao, Fu Jin, Zhang Yu, Yang Xiaomin, Ren Mulan, Zeng Xiaoqin, Li Xiaodong, Tang Lianglian, Duan Jie, Liu Yan, Gan Jingwen, Guo Yingying, Liang Wanqi, Wang Yu, Xue Wei, Deng Yan, Wang Yanfang, Sun Aijun
National Clinical Research Center for Obstetric & Gynecologic Diseases, Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Department of Reproductive Endocrinology, West China Second University Hospital, Sichuan University; Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Chengdu, Sichuan Province, China.
J Transl Int Med. 2025 Jul 8;13(4):349-365. doi: 10.1515/jtim-2025-0027. eCollection 2025 Aug.
Oligomenorrhea and hypomenorrhea were common conditions in outpatient visit which affected child-bearing aged women, and the conventional progesterone treatment has been related to several side effect and contradiction, and this study aimed to evaluate the effectiveness and safety of traditional Chinese medicine (TCM), progesterone capsules, and their combination in treating oligomenorrhea and hypomenorrhea both clinical and metabolomic approach.
A prospective, randomized, multi-center trial has been conducted, and a total of 239 oligomenorrhea and hypomenorrhea were randomly assigned to receive TCM, progesterone capsules (PG), or the combined Chinese and Western medicine (COM) and treated from 3 months, respectively. Scores were recorded at 1 and 3 month of treatment, while the seral samples for sex hormone and safety parameters were taken before and after management, with adverse events recorded. A post-hoc metabolomic research was further conducted, in which a total of 84 patients' blood sample collected before and after 3-month treatment were screened liquid chromatography-tandem mass spectrometry (LC-MS) and the results were analyzed with machine learning models to identify the differential metabolites, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database and Interactive pathways explore (iPath) database were applied to unveil the potential pathway involved in the treatment.
A total of 220 participants completed the trial treatment, with dropout rate of 11.6%. The Traditional Chinese Medicine Syndrome Scale (TCMSS) scores of each group were significantly lower than those before treatment after 1 month of treatment and after 3 months of treatment. After 3 months of treatment, the COM group had the highest total effective rate (61.54%). The pictorial blood loss assessment chart (PBAC) scores in the TCM group were significantly higher than those before treatment after 1 month of treatment and 3 months after treatment, whereas no difference before and after treatment was observed within PG group. In COM group, the score after 3 months of treatment was significantly higher than that before treatment. In the post-hoc study with metabolomic approach with KEGG pathway enrichment and topological analyses, glycerophospholipid (GPL) metabolism were found significantly altered in all 3 groups. while TCM could potentially improve the clinical symptom tryptophan metabolism.
From the perspective of TCMSS scores, the effect of COM group is more significant. In terms of PBAC scores, sex hormone level, endometrium and the improvement of ovarian function in patients with low ovarian function, the TCM group had a better response. In a comprehensive evaluation, the regimen of TCM alone or COM can significantly improve menstrual flow and treat oligomenorrhea and hypomenorrhea patients. With KEGG pathway enrichment and topological analyses, GPL metabolism were found significantly altered in all 3 groups, and TCM could potentially improve the clinical symptom tryptophan metabolism. Whereas unique pathways influenced under combo treatment suggested a synergetic effect of combination TCM with western medicine in management of oligomenorrhea and hypomenorrhea.
月经过少和经量过少是门诊常见病症，影响育龄期女性，传统孕激素治疗存在多种副作用和禁忌，本研究旨在采用临床和代谢组学方法评估中药、黄体酮胶囊及其联合用药治疗月经过少和经量过少的有效性和安全性。
进行了一项前瞻性、随机、多中心试验，共239例月经过少和经量过少患者被随机分为中药组、黄体酮胶囊（PG）组或中西医结合组（COM），分别接受3个月治疗。在治疗1个月和3个月时记录评分，同时在治疗前后采集血清样本检测性激素和安全参数，并记录不良事件。进一步进行事后代谢组学研究，对3个月治疗前后收集的8例患者血样进行液相色谱-串联质谱（LC-MS）筛查，结果用机器学习模型分析以识别差异代谢物，并应用京都基因与基因组百科全书（KEGG）通路数据库和交互式通路探索（iPath）数据库揭示治疗中涉及的潜在通路。
共220名参与者完成试验治疗，脱落率为11.6%。各治疗组中医证候量表（TCMSS）评分在治疗1个月和3个月后均显著低于治疗前。治疗3个月后，COM组总有效率最高（61.54%）。中药组治疗1个月和3个月后图像失血评估图（PBAC）评分显著高于治疗前，而PG组治疗前后无差异。COM组治疗3个月后的评分显著高于治疗前。在采用KEGG通路富集和拓扑分析的事后代谢组学研究中，发现所有3组甘油磷脂（GPL）代谢均有显著改变。而中药可能通过色氨酸代谢改善临床症状。
从TCMSS评分来看，COM组疗效更显著。从PBAC评分、性激素水平、子宫内膜及低卵巢功能患者卵巢功能改善情况来看，中药组反应更佳。综合评估，单用中药或COM方案均可显著改善月经量，治疗月经过少和经量过少患者。通过KEGG通路富集和拓扑分析，发现所有3组GPL代谢均有显著改变，中药可能通过色氨酸代谢改善临床症状。而联合治疗影响的独特通路提示中西医结合治疗月经过少和经量过少具有协同作用。
