目的：PCOS是育龄期女性最常见的内分泌疾病之一，影响女性生命时间跨度广，患病率波动在9%-18%。PCOS是以生殖内分泌功能紊乱及代谢异常为突出表现的综合征，由于无法用单一病因解释及其发病机制及相关环境因素尚未明了，目前缺乏病因治疗，疾病本身及其相关并发症对医疗体系造成巨大负担。随循证医学证据的丰富，PCOS临床诊疗方案不断进步。传统中医药在治疗月经失调中有具有悠久历史，受众广。但由于治疗强调个体化辨证施治，高级别循证医学证据不足。西药显效快，但存在不良反应不耐受的问题，因此本研究拟探索中西医协同治疗PCOS是否可优势互补、减副增效。

方法：本研究通过线上问卷的方式调查从业医生对PCOS的诊治现状，比较国内从业者对PCOS的诊治现状与国内外循证证据间的异同。采取单中心、前瞻性、平行、随机对照的研究临床研究探究补肾中成药金凤丸及达英-35单用及二者联合使用对PCOS患者治疗的疗效及安全性，随机分为3组分别接受金凤丸（中药组）、达英-35（西药组）及金凤丸联合达英-35（联合组）治疗3个月，观察治疗后患者的雄激素水平、高雄激素体征、月经情况、糖脂代谢及安全性指标。通过采集治疗前后患者的血浆及粪便标本，采用液相色谱非靶向代谢组学技术及16S rRNA基因测序技术分析治疗前后血清代谢组学及粪便肠道菌群变化，进一步探索代谢通路改变及可能药效机制。

结果：现状调查共纳入4932份问卷进行分析，受试者多数为妇产科医生（非亚专科），生殖与妇科内分泌医生仅占2.8%。多数受试者年龄在36-55岁之间，工作于三级及二级医院。受试者对治疗方式选择各选择分布不均匀，调整生活方式及二甲双胍为受试者的主要选择。各年资对无生育需求患者治疗选择存在差异（p<0.05），其中行医年限＞20年的医生对二甲双胍普及率最高。不同专业领域受试者对有生育需求患者治疗方式选择存在差异（p<0.001）。对于来曲唑的选择生殖/妇科内分泌专科医生认可度最高，远高于其他妇产科医生。

单中心随机对照临床试验共有115名患者接受随机化分组，最终106名患者完成临床试验随访（中药组36名、西药组34名、联合组36名），总脱落率为7.8%。治疗3个月后西药组及联合组患者性激素变化显著，西药组睾酮由0.66±0.24ng/mL下降至0.59±0.25ng/mL；联合组睾酮由0.70±0.21ng/mL下降至0.62±0.24ng/mL，p<0.05。治疗后3组的痤疮评分均较前显著降低，p<0.05；毛发评分均较基线水平降低，但无统计学差异。治疗期间联合组月经规律患者占比最高（94.4%）。对于血糖代谢，三组患者在干预前后的血糖、胰岛素、糖化血红蛋白及HOMA-IR水平经组内分析均未显示出显著变化。对合并胰岛素抵抗患者亚组分析显示，联合组治疗后2h胰岛素较治疗前下降明显，p<0.05。血脂指标显示，治疗后西药组及联合组TC、TG、HDL和ApoA1较治疗前显著性升高，西药组Lp(a)较治疗前显著性降低。中药组及联合组健康状况调查问卷SF-36评分较治疗前显著提高，p<0.05；各组患者治疗1个月、2个月及完成治疗后月经相关中医证候量化表均较基线明显下降，p<0.05。

代谢组学轮廓分析显示三组治疗均能够显著调控血清代谢物谱，中西医结合治疗在调节PCOS患者血清VIP代谢产物方面展现出协同作用，KEGG富集分析显示3个独立治疗组均显著性地聚焦于类固醇激素的生物合成及脂肪酸代谢这两个领域，但在具体作用焦点上展现出明显的差异性。中药组的主要代谢活动紧密围绕在脂代谢及炎症相关的途径上；西药组则主要涉及类固醇激素的合成及不饱和脂肪酸的代谢通路；联合组不仅在脂代谢、类固醇激素合成这两条通路上有显著富集，且与炎症反应调控紧密相关。肠道菌群研究结果显示，各组在肠道微生物健康指数及微生物失调指数角度治疗后均有显著改善。单中药治疗PCOS患者肠道菌群的β多样性显著降低，而西药治疗及联合治疗后PCOS患者肠道菌群的β多样性显著升高。门水平上中西药联合治疗后髌骨细菌门的丰度显著升高；在属水平上3种治疗方式均能够调节肠道菌群结构。Lefse多级物种差异判别分析显示中西药联合使用能够影响患者肠道菌群的多层级结构。

结论：现状调查研究显示目前国内妇产科医师对PCOS患者治疗选择符合临床指南，能重视生活方式调整及胰岛素抵抗相关治疗。单中心、平行、随机对照临床试验证实中药、西药、中西药联合治疗安全有效，均可改善临床高雄体征。西药和中西药可有效规律月经，降低雄激素水平；中药及中西药可有效改善患者生活质量，3种治疗方式均能有效降低中医证候评分；胰岛素抵抗人群亚组分析提示中西药结合一定程度上能改善胰岛素抵抗。中西联合方案能够多维度、多靶点地作用于PCOS病理生理过程，在血清代谢组学及肠道菌群中显现出协同作用。综上，中药金凤丸联合西药达英-35治疗PCOS在一定程度上优于单西药或单中药治疗。

Aims: Polycystic ovary syndrome (PCOS), a prevalent endocrine-metabolic condition, predominantly affects individuals during their childbearing years, with a prevalence fluctuating from 9%-18%. PCOS is a syndrome characterized by reproductive endocrine dysfunction and metabolic abnormalities, and is currently lacking in etiologic treatment due to the fact that it is unexplainable by a single etiologic agent, and its pathogenesis and associated environmental factors are not yet understood, and that the disease and its associated complications place a huge burden on the healthcare system. PCOS and associated complications have placed a huge burden on the healthcare system. With the abundance of evidence-based medicine, clinical protocols for the diagnosis and management of PCOS have continued to progress. Traditional Chinese medicine (TCM) has a long history of treating menstrual disorders and is widely accepted. However, due to the individualized treatment, there is a lack of high-level evidence. Western medicines show quick effect, but with the problem of intolerance of adverse effects, so this study intends to explore whether the synergistic treatment of PCOS with Chinese and Western medicines can complement each other's strengths, reduce the side-effects and increase the efficacy.

Methods: An online questionnaire was used to investigate the current status of doctors' consultation and treatment on PCOS, to compare the similarities and differences between the current status of domestic practitioners' opinions on PCOS and domestic and international evidence-based evidence. A single-center, prospective, parallel, randomized controlled clinical study was conducted to investigate the efficacy and safety of the TCM Jinfeng Pill and Diane-35 alone and in combination in the treatment of patients with PCOS. Three groups were randomly divided into three groups to receive Jinfeng Pill (TCM group), Diane-35 (western medicines group), and Jinfeng Pill and Diane-35 (combination group) for 3 months, and to observe androgen levels, hyperandrogenic signs, menstrual cycles, glucose and lipid metabolism and safety parameters. Plasma and fecal specimens were collected before and after treatment, and liquid chromatography non-targeted metabolomics and 16S rRNA gene sequencing were used to analyze the changes in serum metabolomics and gut microbiota before and after treatment, to further explore the changes in metabolic pathways and the possible mechanisms.

Results: A total of 4932 questionnaires were included in the current status survey for analysis. The majority of subjects were obstetricians and gynecologists (non-subspecialists), with reproductive and gynecological endocrinologists accounting for only 2.8%. Most of the subjects were between 36-55 years of age and worked in tertiary and secondary hospitals. Subjects' choice of treatment modality was unevenly distributed across choices, with lifestyle modification and metformin being the main choices of the subjects. There was a difference in the choice of treatment for patients without fertility needs by seniority (p<0.05), with the highest prevalence of metformin among physicians who had practiced medicine for >20 years. There was a difference in the choice of treatment for patients with fertility needs among subjects with different areas of specialization (p<0.001). The highest endorsement for letrozole choice was among reproductive/gynecologic endocrine specialists, much higher than other obstetricians and gynecologists.

A total of 115 patients were randomized in the single-center randomized controlled clinical trial, and 106 patients eventually completed the clinical trial follow-up (36 in TCM group, 34 in the Western medicine group, and 36 in the combination group), with an overall shedding rate of 7.8%. After 3 months of treatment, patients in the western medicine group and the combination group showed significant changes in sex hormones, with testosterone decreasing from 0.66±0.24 ng/mL to 0.59±0.25 ng/mL in the western medicine group; and testosterone decreasing from 0.70±0.21 ng/mL to 0.62±0.24 ng/mL in the combination group, p<0.05. Acne scores were significantly lower in all three groups, p<0.05 ; Ferriman-Gallway scores were all reduced from baseline levels, but without statistical difference. The combined group had the highest percentage of patients with regular menstruation during treatment (94.4%). For glucose metabolism, no statistical differences were observed in the intragroup comparison of blood glucose and insulin, glycosylated hemoglobin, and HOMA index pre- and post-treatment in all three groups. Subgroup analysis of patients with insulin resistance showed that insulin at 2h decreased significantly in the combined group after treatment compared with before treatment, p<0.05. Lipid parameters showed that TC, TG, HDL and ApoA1 increased significantly in the western medicine group and the combined group, and Lp(a) decreased significantly in the western medicine group after treatment. The SF-36 score of the health status questionnaire in the TCM group and the combined group was significantly higher than before treatment, p<0.05; the TCMSS decreased significantly from baseline in all groups at 1 month, 2 months and after completion of treatment, p<0.05.

Metabolomics profile analysis showed that all three treatment groups were able to regulate serum metabolite profiles, and the combination of TCM and Western medicine treatment demonstrated synergistic effects in regulating serum VIP metabolites in PCOS patients. KEGG enrichment analysis showed that the three independent treatment groups were significantly focused on the domains of steroid hormone biosynthesis and fatty acid metabolism, but variability was demonstrated in their specific focuses of action. The main metabolic activities of the TCM group were closely centered on lipid metabolism and inflammation-related pathways; the Western medicine group was mainly involved in steroid hormone synthesis and unsaturated fatty acid metabolism pathways; and the combination group was not only enriched in lipid metabolism and steroid hormone synthesis, but was also closely related to the regulation of inflammatory response. The results of the study on gut microbiota showed that there was a significant improvement in GMHI and MDI. The β-diversity in PCOS patients treated with TCM was significantly lower, while that was significantly higher after western medicine treatment and combination treatment. The abundance of patellar bacterial phylum was significantly higher after the combination treatment at the phylum level, and all three treatments were able to regulate the structure of the intestinal flora at the genus level. Lefse analysis showed that the combination of Chinese and Western medicines was able to influence the multilevel structure of the intestinal flora.

Conclusions: The present study showed that obstetricians and gynecologists in China are in compliance with the clinical guidelines for the treatment of patients with PCOS, and are able to pay attention to lifestyle modification and insulin resistance-related treatments. Single-center, parallel, randomized controlled clinical trials confirm that TCM, western medicine, and their combination are safe and effective in PCOS management, and all of them can improve hyperandrogenism. Western medicine and the combination can effectively regulate menstruation and reduce serum androgen levels; TCM and the combination can effectively improve the quality of life of patients, and all three treatment can effectively reduce TCMSS; subgroup analysis of the insulin resistance population suggests that the combination of  TCM and Western medicines can improve insulin resistance , to a certain extent. The combination of Chinese and Western medicines can act on PCOS in a multi-dimensional way, and show synergistic effects in serum metabolomics and gut microbiota. In conclusion, the combination of Chinese medicine Jinfeng Pill with western medicine Diane-35 for the treatment of PCOS is superior to single western medicine or single TCM treatment.