TCM Treatment of Endometriosis: Pathogenesis, Mechanism and Clinical Practice

Endometriosis (EMs) is a chronic neuroinflammatory disorder dominated by intractable chronic pelvic pain, affecting approximately 6–10% of women of reproductive age. 1 Historically, definitive diagnosis of EMs relied on intraoperative confirmation of ectopic endometrial tissues outside the uterine cavity. Endometriotic lesions can also be detected in asymptomatic individuals, and the positive detection rate reaches 50% among infertile female patients receiving clinical assessment. 2 The classical pathological definition of EMs refers to ectopic distribution of endometrial tissues outside the uterus. Nevertheless, marked inter-individual heterogeneity exists in lesion phenotypes and symptomatic severity across patients. Chronic inflammatory activation and excessive estrogen accumulation are acknowledged core pathological characteristics of EMs, yet the exact pathogenic mechanism has not been fully elucidated. 3 Such complexity originates from multi-factor joint effects, including genetic susceptibility, endocrine disturbance, environmental exposure and immune dysfunction, which have been validated by cumulative research evidence. 4 First-line clinical interventions for EMs mainly consist of lesion resection surgery and long-term hormonal regulation. Conventional western therapies are limited by obvious adverse reactions and unstable therapeutic effects. 5 Annual medical expenditure for EMs patients reaches thousands of US dollars, comparable to the economic burden of type 2 diabetes, Crohn’s disease and rheumatoid arthritis. 6 EMs imposes severe physical discomfort and psychological stress on female patients, while pathogenic research and standardized therapeutic regimens still have obvious room for improvement. 7 , 8 As a typical complementary and alternative therapy, Traditional Chinese Medicine (TCM) has accumulated abundant long-term clinical experience for EMs management, featuring diversified intervention modalities and mild safety profiles without severe iatrogenic discomfort, which has gained rising academic attention in recent years. Most existing TCM reviews for EMs merely summarize clinical efficacy or single-pathway mechanistic findings separately, with few reports linking classical TCM theoretical frameworks (the fu xie (latent pathogen) theory and luo bing (collateral disease) theory) to modern multi-omics molecular evidence. To fill this research gap, the present review firstly systematically sorts out the epidemiological characteristics, genetic pathogenesis, diagnostic strategies and pathological progression of EMs, then innovatively interprets the therapeutic characteristics of TCM against EMs by integrating TCM classical pathogenesis theories and multi-omics mechanistic data, further summarizes clinical application, existing controversies and research limitations of integrated Chinese and western medicine schemes, so as to provide novel theoretical references for subsequent basic research and clinical standardized formulation of TCM for endometriosis.

This narrative review systematically collects, sorts and summarizes domestic and foreign literature on the pathogenesis, diagnostic progress, Western medicine treatment, TCM theoretical connotation, molecular mechanism and clinical practice of endometriosis (EMs). The literature retrieval databases include PubMed, Web of Science, Cochrane Library, CNKI, Wanfang and VIP Chinese database. Search keywords were set as “endometriosis”, “adenomyosis”, “pathogenesis”, “diagnosis”, “surgery”, “hormone therapy”, “traditional Chinese medicine”, “Chinese herbal compound”, “acupuncture”, “blood stasis”, “inflammation”, “immune regulation”, “signal pathway”, combined with Boolean operators AND/OR for cross retrieval. The retrieval time range was from database establishment to May 2025. Inclusion criteria: (1) Original research articles, systematic reviews, meta-analyses and authoritative clinical guidelines focusing on EMs pathogenesis, diagnosis and integrated Chinese-Western treatment; (2) Studies exploring TCM etiology, molecular mechanisms and randomized controlled clinical trials of herbal medicine/acupuncture for EMs; (3) Literatures published in Chinese or English with complete data and clear experimental design. Exclusion criteria: (1) Repeatedly published articles, conference abstracts, case reports with small single samples; (2) Reviews lacking systematic literature sorting and experimental original articles with serious design defects; (3) Literature with incomplete experimental data, unclear grouping and inconsistent statistical results. After initial screening by reading titles and abstracts, irrelevant duplicate literatures were eliminated, and the remaining eligible papers were read in full text for data extraction. The extracted information covered epidemiological data, genetic and pathological molecular pathways, Western standardized intervention schemes, TCM core pathogenesis theories, multi-target pharmacological mechanisms of commonly used prescriptions, clinical trial design, efficacy indicators, safety adverse reactions as well as existing research disputes and standardized bottlenecks. On this basis, this review combed the internal logical chain from disease basic research to clinical integrated Chinese-Western intervention, objectively analyzed the advantages and limitations of TCM as an adjuvant therapy, and put forward targeted standardized and translational research directions in combination with the deficiencies of current evidence. EMs are usually diagnosed in individuals in their early 30s, although on average symptoms appear in adolescence through their early 20s. 5 , 9 Although in the general population, the prevalence of EMs in women of childbearing age is 10%, 10 a systematic review of 69 observational studies reported that the prevalence varies widely, depending on geographic location, symptoms, age, and diagnostic method. 10 A meta-analysis of 11 observational studies showed that EMs were detected in 28.1% of women presenting for chronic pelvic pain, while another meta-analysis of 17 observational studies showed that the disease was detected in 24.8% of women presenting for infertility, with these observations mostly made by laparoscopy 5 , 9 17). Knowledge of population distribution, disease presentation, and risk factors is limited to data on women with a successful diagnosis of EMs. The number and characteristics of the confirmed case are unknown. (See Figure 1 ). Figure 1 Epidemiological and genetic framework of EMs. The central schematic represents EMs as the disease entity. Bold headings “Epidemiology” and “Genetics” mark two complementary domains linked by lateral arrows. Epidemiology summarizes typical diagnosis around age 30, ~10% prevalence in reproductive-age women, and higher detection among women with chronic pelvic pain (CPP, 28.1%) and infertility (24.8%). Genetics summarizes ~50% heritability from twin studies, GWAS risk SNPs in severe EMs, implicated pathways (estrogen signaling, MAPK, Wnt, IL-1A), and shared genetic architecture with infertility, uterine fibroids, and cancer. Together, the figure provides a dual-axis background (population burden and genetic susceptibility) for subsequent mechanistic and TCM-focused sections. A diagram of endometriosis showing epidemiology and genetics factors linked by arrows. Epidemiological and genetic framework of EMs. The central schematic represents EMs as the disease entity. Bold headings “Epidemiology” and “Genetics” mark two complementary domains linked by lateral arrows. Epidemiology summarizes typical diagnosis around age 30, ~10% prevalence in reproductive-age women, and higher detection among women with chronic pelvic pain (CPP, 28.1%) and infertility (24.8%). Genetics summarizes ~50% heritability from twin studies, GWAS risk SNPs in severe EMs, implicated pathways (estrogen signaling, MAPK, Wnt, IL-1A), and shared genetic architecture with infertility, uterine fibroids, and cancer. Together, the figure provides a dual-axis background (population burden and genetic susceptibility) for subsequent mechanistic and TCM-focused sections. Clinically confirmed EMs mainly include superficial peritoneal (80%), ovarian cystic and deep infiltrating subtypes, and lesions may also occur in extrapelvic tissues and nervous systems. 6 , 11 , 12 EMs lack reliable non-invasive serum biomarkers for routine clinical screening; a systematic review covering 141 trials and 122 biomarkers confirmed no indicator possesses adequate diagnostic accuracy, with most relevant studies limited by insufficient sample size and flawed design. 13 , 14 Laparoscopy is the gold standard for EMs diagnosis. Transvaginal ultrasound and MRI can detect deep lesions and adhesions (MRI sensitivity 94%, specificity 79%), but cannot identify superficial peritoneal lesions effectively. 14 , 15 Most patients start experiencing pelvic pain during adolescence, yet delayed diagnosis is common. Surgical evaluation is only recommended for severe symptoms, and referral criteria differ by clinicians and medical accessibility. Long diagnostic delay leads to persistent pain, mental burden and fertility damage. 16 , 17 (See Figure 2 ). Figure 2 Clinical classification and diagnostic strategies for endometriosis. The top node “EMs” branches into Classification and Diagnosis, displayed in bold. The figure summarizes the major phenotypes of EMs, including superficial peritoneal, ovarian, deep infiltrating, and extrapelvic disease, together with the principal diagnostic approaches. Although laparoscopy remains the diagnostic gold standard because of its ability to directly visualize endometriotic lesions, its invasive nature represents an important clinical limitation. Transvaginal ultrasonography and magnetic resonance imaging (MRI) provide valuable non-invasive approaches, particularly for the detection of deep infiltrating endometriosis and pelvic adhesions. The absence of reliable non-invasive biomarkers remains a major unmet need in the diagnosis of EMs. Diagram of EMs classification and diagnosis strategies. Clinical classification and diagnostic strategies for endometriosis. The top node “EMs” branches into Classification and Diagnosis, displayed in bold. The figure summarizes the major phenotypes of EMs, including superficial peritoneal, ovarian, deep infiltrating, and extrapelvic disease, together with the principal diagnostic approaches. Although laparoscopy remains the diagnostic gold standard because of its ability to directly visualize endometriotic lesions, its invasive nature represents an important clinical limitation. Transvaginal ultrasonography and magnetic resonance imaging (MRI) provide valuable non-invasive approaches, particularly for the detection of deep infiltrating endometriosis and pelvic adhesions. The absence of reliable non-invasive biomarkers remains a major unmet need in the diagnosis of EMs. Twin studies demonstrate EMs heritability up to 50%, and cross-regional GWAS have uncovered disease-related SNPs, yet they cannot analyze rare variants. 13 , 18–20 Shared risk SNPs exist between EMs and infertility, uterine fibroids and gynecological malignancies, all hormone-dependent disorders; a GWAS meta-analysis found five EMs susceptibility loci linked to sex steroid pathways, alongside MAPK, IL-1A and Wnt signaling genes, with shared genetic links to migraine, depression and bowel disorders. 20–27 Traditional GWAS only interpret adjacent genes, ignoring long-range regulatory elements; integrating transcriptome data can better screen risk genes, a method validated in breast and ovarian cancer research. A transcriptomic study of 200+ women found 39 endometrial differential genes, five overlapping GWAS loci, calling for more eQTL research. 28–30 Epigenetic regulation is a hot EMs research field. Distinct Wnt-related methylation patterns and abnormal endometrial DNA methylation altering estrogen response have been validated. 31 , 32 Exome sequencing on deep EMs detected somatic cancer-related mutations in lesions; age-related spontaneous mutations also occur in normal endometrium, without higher cancer risk for deep EMs. Such mutations affect lesion cell development and therapeutic sensitivity. 33–35 Local inflammation and immune dysregulation are characteristic of EMs, but whether they are the cause or consequence of the disease remains to be elucidated. 36 , 37 Therefore, understanding why ectopic, but not eutopic, endometrium tends to become inflamed is fundamental to developing new therapeutic options for this disease, as inflammation and subsequent fibrosis are responsible for major clinical signs and symptoms, including pelvic pain, bowel and urinary problems, and infertility. There is substantial evidence that EMs are inflammatory. Several key inflammatory mediators, including COX-2, IL-1β, IL-8, tumor necrosis factor (TNF) -α, PEG2, and E2, are elevated in endometriotic lesions compared with eutopic endometrium. 38–40 These mediators act synergistically to maintain and exacerbate inflammation. The endometrium of women with EMs exhibits increased COX-2 expression levels compared to the normal endometrium of women without EMs, and EMs tissue has even higher COX-2 levels. In addition, IL-1 β also increases COX-2 expression and therefore upregulates PGE2. 41 Thus, endometriotic stromal cells have elevated levels of PEG2, which induces production of E2, and this in turn promotes local inflammation. Thus, excess E2 and PEG2 form a positive feedback loop and contribute to sustained inflammation, immune response, angiogenesis, and inventory of endometriotic tissue. 42 , 43 Several types of immune cells, including B lymphocytes, 44 macrophages, 45 CD1a + dendritic cells. 46 Natural killer (NK) cells, 47 T regulatory cells, 48 and monocyte myeloid-derived suppressor cells 49 are ubiquitous in the microenvironment of EMs. These immune cells are also present in the peritoneal fluid, where they interact with each other and with the diseased epithelial and stromal cells. Interestingly, increased infiltration of immune cells, especially macrophages, was also found in the eutopic endometrium of patients with EMs, 50 supporting that patients with EMs are different from endometrium without disease, although follow-up studies are needed to validate these findings. Like cancer, EMs resemble chronic wounds that never heal. In cancer, one of the most widely studied inflammatory pathways, NF-κB, orchestrates many aspects of cancer-associated inflammatory phenotypes by coordinating cross-talk between NF-κB. And other signaling pathways, including STAT3, p53, NRF2, JNK, Notch, and the WNT/β-chain protein pathway. 51 NF-κB is biologically involved in various cancer-promoting phenotypes, such as metastasis, angiogenesis, immunosuppression, tumor cell survival and proliferation, cancer stem cell maintenance, and treatment resistance. 51 , 52 NF-κB also appears to play a key role in the development of EMs. 53–55 In endometrial stromal cells, iron overload activates IKKβ and leads to the production of large amounts of reactive oxygen species, which stimulate the NF-κB pathway. Lipopolysaccharide promotes the development of murine EMS-like lesions by activating the NF-κB pathway. 56 While disulfiram, a candidate NF-κB inhibitor, prevented the growth of endometriotic implants in a rat model of EMs. 57 However, increased anti-inflammatory cytokines such as IL-6, IL-10, and TGF-β, as well as soluble NKG2D ligands, MICA, and MICB in the peritoneal fluid can attenuate the proinflammatory effects of PGE2 and NF-κB. 58–62 Several immunosuppressive and immune evasion mechanisms also modulate the immune response of EMs. Recent studies have shown that both PD-L1 and PD-1 are upregulated in endometriotic tissue relative to healthy controls, and that in vitro expression of PD-L1 on endometrial epithelium is induced by E2. 63 These data suggest that the PD-1/PD-L1 pathway may be involved in the immune evasion of EMs. Thus, it appears that a fine balance between pro- and anti-inflammatory mechanisms determines the actual inflammatory phenotype of individual endometriotic lesions. Most papers on EMs refer to them as “estrogen-dependent” diseases. In normal endometrium, the expression of receptors that bind to estrogens (ER.alpha., ER.beta., and GPER1), androgens (AR), progestogens (PRA and PRB), or glucocorticoids (GR and MR) is cell specific and cycle dependent. 64 , 65 Dysregulation of PR expression, including epigenetically programmed changes in the PR promoter, 65 has been detected in endometrial lesions in patients with EMs. These findings are consistent with reports that stromal cells of women with EMs are less responsive to the effects of progesterone, the so-called antiprogesterone effect, 32 thereby causing impaired stromal epithelial cell crosstalk. Increased expression of ERβ in endometriotic lesions and lesion-derived stromal cells has been widely reported. 65 The availability of ERβ-selective agonists prompted their evaluation in the EMs model, with promising results for the compound ERb041 developed by Wyeth. 66 However, the details of the discovery have not been reported to date. 67 These failed trials demonstrate how challenging it can be to design therapies with disease-preventing implications in diseases with complex cellular interrelationships. For example, while ERβ agonists can inhibit the proliferation of epithelial cells, they stimulate angiogenesis and endothelial cell production of regulatory molecules, 68 , 69 and can also affect the function of immune cells, including macrophages. 70 Although there have been promising results from a new generation of ligands that show strong ER-dependent anti-inflammatory activity 71 in a preclinical mouse model of EMs, they have not progressed to clinical trials. Endometriotic lesions are complex multicellular structures, and vascularization, including the growth of new blood vessels, plays a key role in their establishment, survival, and growth. 72 The study of the lesions benefited from the existing knowledge obtained from the profiling of angiogenic factors and angiogenic receptors in human normal endometrium, which showed high levels of expression of angiogenic endothelial growth factor (VEGFA) and nerve growth protein-1 (NRP-1) as major receptor mRNAs. 73 Hypoxia plays an important role in the regulation of gene expression during menstruation. 74 It can stimulate estrogen biosynthesis and estrogen receptor expression in the lesion microenvironment. 75 Reuse of angiostatic therapies by targeting the vascular endothelial growth factor/tyrosine kinase signaling pathway has been explored as a treatment for EMs. 73 However, because tyrosine kinase inhibitors can induce miscarriage and birth defects, concerns have been expressed regarding their use in populations that may be at risk of pregnancy. 76 (See Figure 3 ). Figure 3 Pathophysiological network of EMs and multiple therapeutic targets of TCM. This schematic summarizes the major pathological processes involved in EMs and the corresponding therapeutic mechanisms of TCM. The upper panel highlights three major pathological dimensions of EMs, including local inflammation and immune dysregulation, hormonal dysregulation, and angiogenesis, neuroangiogenesis, and neuroinflammation. These processes involve enhanced inflammatory signaling and the PGE2–E2 positive-feedback loop, NF-κB activation, immune-cell infiltration and immune evasion, estrogen receptor β (ERβ) upregulation and progesterone resistance, as well as hypoxia-associated VEGF/NRP-1 signaling. The middle panel illustrates representative TCM interventions and their potential molecular or targets, including Wenshen Xiaozheng Decoction-mediated inhibition of NF-κB signaling and downregulation of c-IAP1/c-IAP2; blood-activating and stasis-removing herbs-mediated suppression of VEGF and angiopoietin-2 (Ang-2); acupuncture/tripterygium glycosides (TG)-mediated immunomodulation; Xiaoliufang-mediated inhibition of ICAM-1 and MMP-9; Guizhi Fuling Capsule-mediated regulation of serum estradiol (E2); warm needling-mediated modulation of NGF, BDNF, and PGE2; and Shaofu Zhuyu Decoction-mediated regulation of the gut microbiota. These multitarget and multipathway effects collectively contribute to alleviation of pain, reduction of endometriotic lesions or cysts, decreased CA125 and inflammatory markers, improved hemodynamic and endocrine profiles, reduced recurrence, and potential fertility benefits. Rightward arrows (→) denote signaling cascades or promotion; upward/downward arrows (↑/↓) denote increased or decreased expression/activity. The schematic illustrates the pathophysiological network of EMs and therapeutic targets of TCM. Three major pathological dimensions are shown: local inflammation and immune dysregulation, hormonal dysregulation and angiogenesis, neuroangiogenesis and neuroinflammation. Local inflammation includes key mediators like COX-2, IL-1beta, IL-8, TNF-alpha, PGE2 and E2, with processes like NF-kappaB activation and immune evasion. Hormonal dysregulation involves elevated ERbeta in lesions and impaired stromal-epithelial crosstalk. Angiogenesis is linked to hypoxia and VEGF/NRP-1 signaling. TCM interventions include Wenshen Xiaozheng, blood-activating herbs, acupuncture/TG, Xiaoliufang, Guizhi Fuling Capsule, warm needling and Shaofu Zhuyu Decoction, targeting various molecular pathways. Clinical benefits include pain relief, lesion reduction, decreased CA125 and inflammatory markers, improved hemodynamics, reduced recurrence and fertility benefits. EM pathophysiology: inflammation, hormonal issues, angiogenesis; TCM interventions shown. Pathophysiological network of EMs and multiple therapeutic targets of TCM. This schematic summarizes the major pathological processes involved in EMs and the corresponding therapeutic mechanisms of TCM. The upper panel highlights three major pathological dimensions of EMs, including local inflammation and immune dysregulation, hormonal dysregulation, and angiogenesis, neuroangiogenesis, and neuroinflammation. These processes involve enhanced inflammatory signaling and the PGE2–E2 positive-feedback loop, NF-κB activation, immune-cell infiltration and immune evasion, estrogen receptor β (ERβ) upregulation and progesterone resistance, as well as hypoxia-associated VEGF/NRP-1 signaling. The middle panel illustrates representative TCM interventions and their potential molecular or targets, including Wenshen Xiaozheng Decoction-mediated inhibition of NF-κB signaling and downregulation of c-IAP1/c-IAP2; blood-activating and stasis-removing herbs-mediated suppression of VEGF and angiopoietin-2 (Ang-2); acupuncture/tripterygium glycosides (TG)-mediated immunomodulation; Xiaoliufang-mediated inhibition of ICAM-1 and MMP-9; Guizhi Fuling Capsule-mediated regulation of serum estradiol (E2); warm needling-mediated modulation of NGF, BDNF, and PGE2; and Shaofu Zhuyu Decoction-mediated regulation of the gut microbiota. These multitarget and multipathway effects collectively contribute to alleviation of pain, reduction of endometriotic lesions or cysts, decreased CA125 and inflammatory markers, improved hemodynamic and endocrine profiles, reduced recurrence, and potential fertility benefits. Rightward arrows (→) denote signaling cascades or promotion; upward/downward arrows (↑/↓) denote increased or decreased expression/activity. In traditional Chinese medicine, EMs are classified into the categories of “abdominal mass”, “infertility” and “dysmenorrhea” 77 Blood stasis is the pathogenesis of morbidity of EMs. Stagnation of blood stasis produces symptoms over time, which accumulate in the lower abdomen, causing progressive dysmenorrhea, pelvic pain, or even infertility. Blood stasis is the pathological product of the occurrence and development of EMs. 78 Part of the blood in the circulation can not be discharged from the human body, and accumulates for a long time to form blood stasis, which blocks the transportation of Qi and blood, and causes pain, so patients often have pain symptoms. Most patients with EMs have no obvious symptoms in the early stage, only abdominal pain or infertility, which has a certain degree of secrecy. The latent evil is similar to it, which refers to the loss of healthy qi caused by emotional, dietary and other factors, resulting in the invasion of exogenous six excesses or endogenous evil, which occurs over time. Blood stasis stagnates in the human body for a long time, forming latent blood stasis and blocking collaterals. 79–81 Accumulation of blood stasis becomes a symptom, but it does not occur immediately, lying in the body, lingering and repeated, seriously affecting the physical and mental health of patients. The mechanism of traditional Chinese medicine in treating EMs involves multi-target and multi-pathway regulation. Studies have shown that Wenshen Xiaozheng Decoction can induce apoptosis of ectopic endometrial stromal cells by inhibiting NF-κB pathway, down-regulating the expression of anti-apoptotic proteins such as c-IAP1 and c-IAP2, and inhibiting cell migration. 82 Blood-activating and stasis-removing herbs such as safflower and Salvia miltiorrhiza can inhibit angiogenesis and reduce the expression of angiogenic factors such as VEGF and Ang-2 in ectopic lesions. 83 , 84 Traditional Chinese medicine such as Shaofu Zhuyu Decoction can improve the symptoms of EMs by regulating the intestinal flora and increasing the abundance of beneficial bacteria such as Ruminococcaceae. 85 Immunomodulation is an important mechanism of TCM in treating EMs. Tripterygium glycosides combined with gestrinone can reduce the serum levels of TGF-β and IL-10 and regulate the balance of Th1/Th2 86 in patients with EMs. Acupuncture can play a role by regulating the function of immune cells, for example, acupuncture can improve the activity of NK cells and enhance their ability to remove ectopic endometrial cells. 87 In addition, traditional Chinese medicine can inhibit the proliferation and invasion of ectopic endometrial cells, such as Xiaoliufang, which can inhibit cell adhesion and invasion by reducing the expression of ICAM-1, MMP-9 and other genes. 88 Traditional Chinese medicine can also play a role by regulating hormone levels, such as Guizhi Fuling Capsule can reduce the serum E2 level of EMs patients and inhibit the growth of ectopic endometrial tissue. 89 Du Bingxin et al 90 designed a RCT to explore the clinical efficacy of Bushen Shugan Xiaozheng Decoction on ovarian endometriosis (OEM) with liver depression, kidney deficiency and blood stasis syndrome. A total of 62 OEM patients were treated with dienogest and dienogest combined with Bushen Shugan Xiaozheng Decoction respectively. The TCM syndrome scores, visual analogue scale (VAS) pain scores, COX dysmenorrhea symptom scale scores (CMSS), IL-6 levels, IL-10 levels, carbohydrate antigen 125 (CA125) levels, ovarian endometriosis cyst size, clinical total effective rate and incidence of adverse reactions were compared between the two groups before and after treatment, and the recurrence rate was compared between the two groups. Conclusion Bushen Shugan Xiaozheng Decoction is effective in the treatment of OEM, which can reduce the inflammatory reaction, reduce the focus, reduce the level of CA125, and is safe in clinical application, and reduce the recurrence. Risk of bias assessment for this trial revealed low risk in random sequence generation, complete outcome data and selective reporting, while high risk was identified in allocation concealment, blinding of participants and outcome assessors, as well as other bias originating from its single-center design and short follow-up period limited to merely 3 menstrual cycles. Major limitations of the study consisted of a small sample of only 62 subjects and the absence of a placebo control; subjective measurements such as VAS pain scale and TCM syndrome scores might introduce observer bias, and no follow-up longer than one year was performed, making long-term recurrence and efficacy unevaluated. In terms of therapeutic comparison, dienogest monotherapy can rapidly decrease CA125 and reduce cyst size but bears the risk of liver injury, whereas combined treatment with Bushen Shugan Xiaozheng Decoction helps lower recurrence and improve emotional discomfort. However, conclusions drawn from this trial are supported by low-level evidence, and large-sample double-blind trials are still necessary for further validation. Wang Tingting et al 91 designed a RCT to observe the clinical efficacy of Quyu Jiedu Fang on EMs patients with kidney deficiency and blood stasis syndrome and the effect of Quyu Jiedu Fang on the expression level of oncogene Jun (c-Jun) N-terminal kinase (JNK) signaling pathway related proteins. In this study, 72 patients with EMs of kidney deficiency and blood stasis were randomly divided into treatment group and control group, with 36 cases in each group. Another 36 patients who underwent in vitro fertilization-embryo transfer (IVF-ET) due to male factor alone were selected as the blank group. The patients in the treatment group were treated with Zishen Quyu Jiedu Decoction, while the patients in the control group and the blank group were treated with placebo. The course of treatment was one cycle before ovarian stimulation and one cycle of oocyte retrieval. The scores of traditional Chinese medicine syndromes of kidney deficiency and blood stasis and the levels of serum cancer antigen 125 (CA125) were evaluated before treatment and after treatment. The levels of serum sex hormones were measured on the second day of menstruation. The days and dosage of gonadotropin (Gn) and the hormone level on the day of human chorionic gonadotropin (HCG) injection were measured on the day of trigger; the embryo outcome was evaluated on the 3rd day after oocyte retrieval; the clinical pregnancy rate was evaluated on the 28th day after embryo transfer. The baseline data of the three groups, the TCM syndrome score between the two groups before and after treatment, the serum CA125 level before and after treatment, the serum sex hormone level, Gn days, Gn dosage, HCG hormone level, the number of retrieved oocytes, the number of fertilized eggs of two pronuclei (2PN), the number of available embryos, the rate of high-quality embryos and the clinical pregnancy rate of the three groups were observed. Expressions of JNK, c-Jun and nuclear receptor subfamily 4A member 2 (NR4A2) proteins in follicular fluid granulosa cells (GCs) of the three groups on the day of oocyte retrieval were detected by Western blot. Conclusion ZSQYJD can significantly improve the clinical signs and symptoms of endometriosis patients with deficiency of the kidney and blood stasis syndrome, reduce the serum CA125 level, increase the number of retrieved oocytes, the number of 2PN fertilization, the number of available embryos, improve the rate of high-quality embryos, and improve the pregnancy outcome, which may be related to the down-regulation of JNK, c-Jun, NR4A2 levels to improve the apoptosis of ovarian granulosa cells. It is related to inhibiting apoptosis and improving ovarian function. Risk of bias evaluation of this trial showed low risks in random sequence generation, complete outcome data and selective reporting, whereas high risks existed in allocation concealment, blinding of participants and outcome assessors, as well as other biases including single-center setting and limited follow-up duration; this study had an overall sample size of 108 with small subgroups, only a minority of patients underwent granuloprotein detection which limited the representativeness of relevant test results, and it lacked long-term pregnancy follow-up and double-blind design, resulting in subjective bias in the assessment of TCM syndromes and pregnancy outcomes. As for the comparison between single and combined regimens, IVF alone merely addresses fertilization without improving the pelvic ectopic microenvironment, which tends to reduce embryo implantation rates, while adjunct Zishen Quyu Jiedu Decoction can regulate the JNK pathway and inhibit granulosa cell apoptosis to increase the number of retrieved oocytes and high-quality embryos; nevertheless, the evidence grade of this study is low, and multicenter, large-sample trials are still needed to confirm its long-term fertility-promoting benefits. Bi Qiuying et al 92 designed a RCT to explore the possible mechanism of Guizhi Fuling Capsule in the treatment of EMs based on EGFR/PI3K/AKT signaling pathway. In this study, 146 patients with EMs were randomly divided into control group and observation group with 73 cases in each group. Two groups of EMs patients were treated with Gestrinone Capsules, and the observation group was treated with Guizhi Fuling Capsules, both groups were treated for 3 menstrual cycles. The digital analogue scale (NRS) of pain, quality of life (EHP-30), lesion area, uterine artery blood flow parameters (RI, PI), serum hormone levels (FSH, E2, LH, P), EGFR/PI3K/AKT signaling pathway related protein expression, therapeutic effect and adverse reactions were recorded before and after treatment in both groups. Conclusion Guizhi Fuling Capsule can relieve pain, reduce lesion area, improve uterine artery blood flow and hormone levels in the treatment of EMs, and its mechanism may be related to the regulation of EGFR/PI3K/AKT signaling pathway. Risk of bias assessment of the trial demonstrated low risks in random sequence generation, complete outcome data and selective reporting, while high risks were found in allocation concealment, blinding of participants and outcome assessors, together with other biases arising from its single-center design and short follow-up of only three menstrual cycles; the study enrolled a total of 146 patients from a single center with short-term observation and no follow-up on recurrence after drug withdrawal, and its efficacy evaluation mainly relied on subjective NRS pain scores without long-term monitoring data of hormonal fluctuations and safety profiles. In terms of therapeutic comparison, gestrinone monotherapy suppresses ectopic endometrial proliferation yet tends to induce menstrual disorders and estrogen fluctuations with prolonged administration, whereas combined treatment with Guizhi Fuling Capsule regulates the EGFR/PI3K/AKT pathway to improve uterine blood flow and relieve pelvic pain, though the lack of a placebo control weakens the reliability of evidence from this trial. Liu Yuling et al 93 designed a RCT to explore the effect of Pingchongjiangni acupoint application combined with abdominal acupuncture on the pregnancy rate and recurrence rate of EMs patients. In this study, 60 patients with endometriosis were selected as the research object and divided into two groups according to the random number table method, with 30 cases in each group. The patients in the control group were treated with mifepristone tablets, while the patients in the observation group were treated with Pingchong Jiangni point application combined with abdominal acupuncture. The TCM syndrome score, estrogen level, therapeutic effect, pregnancy rate, recurrence rate and adverse reactions were compared between the two groups. Conclusion Pingchong Jiangni point application combined with abdominal acupuncture in the treatment of endometriosis can improve traditional Chinese medicine syndrome, reduce estrogen levels, improve the therapeutic effect and pregnancy rate, reduce the recurrence rate and the incidence of adverse reactions, which is worthy of clinical application. Risk of bias assessment for this trial indicated low risks in random sequence generation, complete outcome data and selective reporting, but high risks in allocation concealment, blinding of participants and outcome assessors, along with other biases due to single-center design and short follow-up duration. This study had a small sample size of only 60 patients without a placebo control group; blinding was unachievable for acupoint application treatment, the follow-up period for pregnancy outcomes was relatively short, and long-term monitoring of lesion recurrence after drug discontinuation was absent. In the comparison of therapeutic regimens, oral mifepristone alone could suppress ectopic lesions but brought a high recurrence rate after drug withdrawal, while combined therapy with Pingchong Jiangni Plaster and abdominal acupuncture could stabilize endocrine function, raise pregnancy rates and reduce recurrence. Nevertheless, the reliability of data from this single-center small-sample trial is limited, and further high-quality clinical trials are required to validate these findings. Du Juan et al 94 designed a RCT to explore the efficacy of filiform needle puncture combined with warm needling in the treatment of dysmenorrhea caused by cold coagulation and blood stasis in EMs and the effects on serum inflammatory factors, vascular endothelial growth factor (VEGF), nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF). In this study, 200 patients with EMS cold coagulation and blood stasis syndrome were selected as the research object, and were randomly divided into the control group and the observation group, with 100 cases in each group. The control group was treated with gestrinone, and the observation group was treated with filiform needling combined with warm needling on the basis of the control group. The clinical efficacy, TCM syndrome score, dysmenorrhea score, endometrial hemodynamics [blood flow resistance index (RI), pulsatility index (PI)], inflammatory factors [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and prostaglandin E2 (PGE2)], vascular endothelial growth factor (VEGF)] were compared between the two groups. Nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF). Conclusion The filiform needle cure-needling method combined with warming needle moxibustion has a significant therapeutic effect on em dysmenorrhea with cold coagulation and blood stasis syndrome, which can effectively relieve dysmenorrhea, improve clinical signs and symptoms, and reduce the levels of serum inflammatory factors, VEGF, NGF and BDNF. Risk of bias assessment of this trial showed low risks in random sequence generation, complete outcome data and selective reporting, whereas high risks existed in allocation concealment, blinding of participants and outcome assessors, as well as additional biases stemming from single-center design and relatively short follow-up cycles; although the trial recruited 200 participants, it was conducted in a single center and blinding could not be realized for acupuncture manipulation, with follow-up limited to only three menstrual cycles and no long-term data tracking dysmenorrhea recurrence over years. In the comparison of different treatments, gestrinone monotherapy exerts obvious short-term pain relief but leads to high recurrence of dysmenorrhea after drug cessation, while combined treatment with filiform needle intensive pricking and warm acupuncture can downregulate multiple inflammatory and neuropathic pain factors to sustainably alleviate dysmenorrhea of cold-stagnation and blood-stasis type, yet multicenter replicated trials are still lacking to back up these conclusions. Zhang Chunmin et al 95 designed a RCT to analyze the effect of acupuncture and moxibustion on dysmenorrhea of endometriosis with qi deficiency and blood stasis. In this study, 60 cases of dysmenorrhea due to EMs of qi deficiency and blood stasis type were randomly divided into three groups, 20 cases in the western medicine group (oral drospirenone ethinylestradiol tablets (II)), 20 cases in the traditional Chinese medicine group (decocted granules of traditional Chinese medicine for supplementing qi and removing blood stasis), and 20 cases in the acupuncture group (main points: Zhongwan, Qihai, Guanyuan, Zhongji, etc), and the therapeutic effects of the three groups were compared. Conclusion Acupuncture and moxibustion treatment of endometriosis dysmenorrhea of qi deficiency and blood stasis type can improve the endocrine function and hemodynamic state of patients, enhance the immune function of patients, and improve the analgesic effect. Risk of bias assessment of this trial revealed low risks in random sequence generation, complete outcome data and selective reporting, while high risks were observed in allocation concealment, blinding of participants and outcome assessors, and other biases attributable to single-center design and merely 20 subjects in each group; all three groups had small sample sizes without a blank placebo control group, blinding was impossible for acupuncture and herbal interventions, pain evaluation relied heavily on subjective scoring, and long-term quantitative follow-up data of lesion size were absent. In terms of therapeutic comparison, drospirenone and ethinylestradiol tablets can regulate hormones standardly yet easily cause breast distending pain and mood swings after long-term administration, whereas both qi-tonifying blood-stasis-resolving herbal medicine and acupuncture are capable of improving pelvic blood flow and systemic immunity to relieve dysmenorrhea, though the single-center small-sample design weakens the credibility of relevant conclusions. Yan Ming et al 96 designed a RCT to study the efficacy of Wenyang Huayu Xiaozheng Decoction combined with acupoint acupuncture in the treatment of EMs, and to explore the effects on uterine artery blood flow and serum levels of transforming growth factor-β (TGF-β) and interleukin-17 (IL-17). The study collected 80 cases of EMs patients, according to different treatment methods, 80 cases of EMs patients were divided into combined group (Wenyang Huayu Xiaozheng Decoction combined with acupoint acupuncture) and acupuncture group (acupoint acupuncture). The therapeutic effects, TCM syndrome scores, uterine artery hemodynamic indexes, serum cytokine levels, pain visual analog scale (VAS) scores and the incidence of adverse reactions were compared between the two groups. Conclusion Wenyang Huayu Xiaozheng Decoction combined with acupoint acupuncture can regulate the serum levels of IL-17 and TGF-β in patients with endometriosis, thus reducing the pathological changes of endometriosis and improving the uterine blood flow, which is effective, safe and reliable. Risk of bias assessment of this trial showed low risks in random sequence generation, complete outcome data and selective reporting, but high risks were found in allocation concealment, blinding of participants and outcome assessors, alongside other biases caused by single-center design and short observation period. This single-center trial included only 80 patients, without a Western medicine monotherapy control group or blinding design; cytokines were only detected in the short term, and long-term follow-up data regarding lesion size and disease recurrence were not collected. For therapeutic comparison, acupuncture alone only slightly improves pelvic blood flow and has limited efficacy in inhibiting lesions, whereas combined treatment with Wenyang Huayu Xiaozheng Decoction can downregulate profibrotic and pro-inflammatory factors to reduce ectopic lesions. Nevertheless, the evidence grade is moderately low due to the absence of long-term safety and recurrence follow-up data. Wu Yunfang et al 97 designed a RCT to observe the clinical efficacy of balance acupuncture combined with Biejiajianwan in the treatment of ovarian endometriosis cyst (OEC) with blood stasis syndrome. In this study, 30 patients with OEC blood stasis syndrome were randomly divided into control group and treatment group, 15 cases in each group. The control group was treated with Biejiajian Pill, and the treatment group was treated with balance acupuncture on the basis of the control group. One menstrual cycle was taken as a course of treatment in both groups, and the treatment lasted for 3 courses. The clinical efficacy, TCM syndrome score, visual analogue scale (VAS) score, the maximum diameter of OEC and the level of serum carbohydrate antigen 125 (CA125) were compared between the two groups before and after treatment. Conclusion Balance acupuncture combined with Biejiajian Pill can significantly improve the clinical signs and symptoms of OEC patients with blood stasis syndrome, relieve dysmenorrhea, reduce the size of cyst, and reduce the level of serum CA125, so as to improve the life quality of patients, which is worthy of clinical application. Risk of bias assessment for this trial indicated low risks in random sequence generation, complete outcome data and selective reporting, while high risks existed in allocation concealment, blinding of participants and outcome assessors, as well as other biases resulting from single-center design and an extremely small sample of only 15 patients per group. The total sample size of the study was merely 30 cases with insufficient statistical power due to tiny subgroup capacity; there was no placebo control group, blinding could not be implemented for acupuncture manipulation, follow-up only covered three treatment courses, and long-term monitoring of cyst recurrence was not conducted. In the comparative analysis of therapies, Biejia Jian Pills alone activate blood circulation and dissipate masses yet take a long time to reduce cyst volume, whereas combined treatment with balance acupuncture rapidly relieves dysmenorrhea and decreases CA125 levels, but such an extremely small sample fails to provide sufficient evidence for large-scale clinical promotion of this combined regimen. Zhan Jingfen et al 98 designed a RCT to observe the clinical efficacy of Jiawei Jiaoai Decoction combined with warm acupuncture on EMs patients with cold coagulation and blood stasis. In this study, 86 patients were randomly divided into the control group and the observation group, 43 cases in each group, the control group was given warm acupuncture, the observation group was given Jiawei Jiaoai Decoction on the basis of the control group, the course of treatment was 3 menstrual cycles. The clinical efficacy, TCM syndrome score, dysmenorrhea degree index (VAS score, PGE2, PGF2α), hemodynamic index (RI, PI), sex hormones (E2, FSH, LH), inflammatory factors (IL-1β, IL-6, TNF-α) and the incidence of adverse reactions were detected. Conclusion Jiawei Jiaoai Decoction combined with warming needle moxibustion can safely and effectively regulate the levels of sex hormones and endometrial hemodynamics, inhibit inflammatory reaction and relieve dysmenorrhea in patients with endometriosis of cold coagulation and blood stasis syndrome. Risk of bias assessment of this trial showed low risks in random sequence generation, complete outcome data and selective reporting, whereas high risks were identified in allocation concealment, blinding of participants and outcome assessors, and other biases originating from single-center design and short follow-up limited to three menstrual cycles. This single-center trial enrolled 86 patients without a Western medicine monotherapy control group, merely comparing warm acupuncture alone versus combined acupuncture and herbal medicine; no blinding scheme was adopted, and subjective VAS scores for dysmenorrhea may introduce assessment bias. In terms of therapeutic comparison, warm acupuncture alone only alleviates local pain with limited regulatory effects on systemic hormones and pelvic inflammation, while combined Modified Jiai Decoction simultaneously modulates endocrine function and pelvic inflammatory response. However, the integrity of evidence is insufficient given the lack of head-to-head comparison with first-line hormonal Western medicines. (See Figure 4 ). Figure 4 From traditional Chinese medicine theory to clinical practice: an integrated therapeutic framework for endometriosis. The figure summarizes the TCM-based conceptualization and therapeutic framework of EMs, linking traditional disease cognition with contemporary mechanistic evidence and clinical applications. Vertical progression (blue arrows) indicates the conceptual sequence from TCM cognition to mechanisms and then to clinical application; horizontal arrows expand each level. In TCM theory, EMs is commonly associated with abdominal mass, infertility, and dysmenorrhea, with blood stasis considered a central pathogenic process and latent evil proposed to underlie its insidious and recurrent course. Mechanistically, TCM exhibits pleiotropic effects through the regulation of inflammation and apoptosis, immune responses, angiogenesis, hormonal and metabolic homeostasis, and the gut microbiota. Clinically, these principles are translated into three major therapeutic modalities: Chinese herbal compounds, acupuncture and moxibustion, and integrated TCM–Western medicine treatment. The convergence of these therapeutic approaches may contribute to symptom control, suppression of ectopic lesion growth, improvement of reproductive function, and reduction of recurrence, highlighting the potential of TCM as a multidimensional and integrative therapeutic strategy for EMs. Flowchart: TCM cognition to mechanisms and practice in endometriosis treatment. From traditional Chinese medicine theory to clinical practice: an integrated therapeutic framework for endometriosis. The figure summarizes the TCM-based conceptualization and therapeutic framework of EMs, linking traditional disease cognition with contemporary mechanistic evidence and clinical applications. Vertical progression (blue arrows) indicates the conceptual sequence from TCM cognition to mechanisms and then to clinical application; horizontal arrows expand each level. In TCM theory, EMs is commonly associated with abdominal mass, infertility, and dysmenorrhea, with blood stasis considered a central pathogenic process and latent evil proposed to underlie its insidious and recurrent course. Mechanistically, TCM exhibits pleiotropic effects through the regulation of inflammation and apoptosis, immune responses, angiogenesis, hormonal and metabolic homeostasis, and the gut microbiota. Clinically, these principles are translated into three major therapeutic modalities: Chinese herbal compounds, acupuncture and moxibustion, and integrated TCM–Western medicine treatment. The convergence of these therapeutic approaches may contribute to symptom control, suppression of ectopic lesion growth, improvement of reproductive function, and reduction of recurrence, highlighting the potential of TCM as a multidimensional and integrative therapeutic strategy for EMs. The safety of traditional Chinese medicine in the treatment of EMs is generally good, but there are still some problems. Some traditional Chinese medicines have potential toxicity, for example, Tripterygium glycosides can cause liver injury, leukopenia and other adverse reactions. 86 One study showed that about 10% of patients treated with Tripterygium glycosides combined with gestrinone had abnormal liver function. 86 In addition, the composition of traditional Chinese medicine compound is complex, and there may be drug interactions, for example, the combination with anticoagulants may increase the risk of bleeding. 99 Clinical studies have shown that the incidence of adverse reactions of traditional Chinese medicine in the treatment of EMs is low. A meta-analysis showed that the incidence of adverse reactions of traditional Chinese medicine combined with dienogest was significantly lower than that of western medicine alone. 100 However, attention should be paid to individual differences, for example, patients with allergic constitution may be allergic to some traditional Chinese medicine ingredients. 99 In addition, the quality control of traditional Chinese medicine preparations is also a potential safety hazard, and some preparations may have problems such as excessive heavy metals and pesticide residues. 101 (See Figure 5 ). Figure 5 From current challenges to future directions: advancing traditional Chinese medicine for endometriosis. This schematic highlights the major barriers and prospective priorities for the clinical translation of TCM in EMs. The left panel summarizes the key challenges include safety concerns, particularly hepatotoxicity and individual hypersensitivity or idiosyncratic reactions; methodological limitations of existing clinical evidence; and insufficient elucidation of the molecular mechanisms and potential interactions underlying TCM-based interventions. The right panel presents future directions, encompassing multi-omics and single-cell approaches for mechanistic investigation, biomarker-informed personalized TCM strategies, evidence-based integration of TCM with Western medicine, and enhanced international collaboration and regulatory standardization. Addressing these challenges through rigorous multicenter clinical trials, standardized diagnostic and therapeutic criteria, and mechanistically informed precision approaches may strengthen the evidence base and facilitate the wider clinical and international adoption of TCM for EMs. Infographic comparing challenges and future perspectives in TCM. From current challenges to future directions: advancing traditional Chinese medicine for endometriosis. This schematic highlights the major barriers and prospective priorities for the clinical translation of TCM in EMs. The left panel summarizes the key challenges include safety concerns, particularly hepatotoxicity and individual hypersensitivity or idiosyncratic reactions; methodological limitations of existing clinical evidence; and insufficient elucidation of the molecular mechanisms and potential interactions underlying TCM-based interventions. The right panel presents future directions, encompassing multi-omics and single-cell approaches for mechanistic investigation, biomarker-informed personalized TCM strategies, evidence-based integration of TCM with Western medicine, and enhanced international collaboration and regulatory standardization. Addressing these challenges through rigorous multicenter clinical trials, standardized diagnostic and therapeutic criteria, and mechanistically informed precision approaches may strengthen the evidence base and facilitate the wider clinical and international adoption of TCM for EMs.

This review systematically summarizes the pathogenesis, diagnosis and Western treatment of endometriosis, and correlates modern pathological changes with TCM’s blood stasis theory. Western hormones and surgeries can quickly eliminate lesions but carry obvious side effects and high recurrence rates. TCM formulas and acupuncture act on inflammation, immunity and angiogenesis as adjuvant therapies; combined Chinese-Western treatment relieves pain, reduces cysts and lowers recurrence risk. However, all included RCTs have methodological flaws via Cochrane bias assessment: small single-center samples, no placebo blinding and short follow-ups. There lacks unified TCM syndrome standards, objective biomarkers and clear multi-component mechanisms, plus prevalent publication bias. These shortcomings limit the international recognition of TCM. Major obstacles to global promotion include inconsistent diagnostic criteria, unstable herbal quality and insufficient high-level clinical evidence. To solve these problems, unified TCM evaluation standards and international multi-center double-blind trials are urgently needed. Future research priorities: Use multi-omics to reveal TCM molecular targets; Conduct long-term standardized clinical trials focusing on infertility and postoperative recurrence; Develop stratified integrated Chinese-Western regimens for different disease severities. Sufficient high-quality evidence will boost standardized global application of TCM.