{"paper_id":"1de3bab4-e406-4945-bafd-ba2a0e745c06","body_text":"A benign gynaecological disease, endometriosis (EMs), involves the growth of endometrial tissue outside the uterine cavity, including the myometrium, the ovaries, and the pelvis. It occurs mainly in women of childbearing age, and its clinical manifestations often include dysmenorrhea, abnormal menstruation, chronic pelvic pain, and infertility. It has emerged as a prevalent and challenging disease in clinical gynaecology  [1] . Despite the apparent benign histopathological changes, it has many similarities with invasive tumours. The incidence rate has gradually increased in recent years, showing a trend towards younger patients due to the influence of socioeconomic factors, environment, and cesarean section  [2] .\nCurrently, laparoscopic surgery is the primary clinical treatment for EMs with postoperative medication. However, most patients require long-term medication treatment because of the unknown aetiology of EMs, high recurrence rate, and low pregnancy rate in patients with a prognosis. Therefore, selecting drugs that can effectively prevent recurrence without side effects has become a focus of clinical attention  [3] .  Tripterygium  glycosides are extracts from the xylem fragments of  Tripterygium  roots, used in traditional Chinese medicine to remove wind and dampness, promote blood circulation, and dredge collaterals. Modern pharmacology has demonstrated anti-inflammatory, antibacterial, antitumour, and immunosuppressive effects. Clinical and animal experiments have confirmed that  Tripterygium  glycosides have a significant reversible inhibitory effect on the endometrium and ovaries  [4] . Gestrinone is a commonly used progestogen in clinical practice that can inhibit the growth of the endometrium and ectopic lesions through its anti-gonadotropin and anti-estrogen effects. Here,  Tripterygium  glycosides combined with gestrinone were used to treat patients with EMs, and their effects on serum sex hormone levels, tumour markers, and inflammatory factors were evaluated.\n\nThis study included one hundred eight patients with EMs admitted to our hospital between August 2023 and October 2024.\nInclusion Criteria : All patients met the diagnostic criteria for EMs established by the Chinese Medical Association’s Obstetrics and Gynecology Department’s »Guidelines for the Diagnosis and Treatment of EMs«  [5] . All patients were diagnosed using laboratory tests, ultrasound, and laparoscopy; aged 20–50 years, with no childbearing in the last two years; first-time diagnosis of EMs and no previous treatment; chocolate cyst <6 cm; informed consent and cooperation with treatment from patients and their families; and approval of this study by the hospital’s ethics committee.\nExclusion Criteria : Patients with uterine fibroids and pelvic infections; patients with a history of steroid hormone therapy within six months; allergy to the study drugs; severe hepatic, renal, or systemic immune system dysfunction; pregnant and lactating women; and patients with mental disorders.\nThe patients were divided into the control and treatment groups, with 54 patients in each group. The average age was 32.87±3.25 years, with a disease duration of 4.68±0.79 years. The menstrual cycle lasted 26-30 days, averaging 27.81±4.02 days. There were 38 stage III and 16 stage IV patients. The average age in the control group was 33.75±3.49 years, with a disease duration of 5.16±0.68 years and a menstrual cycle of 27–30 days, with an average of 27.02±5.15 days. The general data of the two groups were comparable (P>0.05) even though there were 35 patients with stage III and 19 with stage IV lesions.\nPatients in the control group were administered oral gestrinone capsules (2.5 mg/capsule, China Resources Zizhu Pharmaceutical Co., Ltd., batch number 20160526) at a dose of 2.5 mg. The first dose was administered on the first day after menstruation, and the subsequent dose was administered three days later, twice a week. Patients in the treatment group were administered  Tripterygium  glycoside tablets (30 mg, Jiangsu Metong Pharmaceutical Co., Ltd., batch number: 20150928) at 20 mg three times a day. After four weeks, the dose was reduced to 10 mg. Both groups were treated for three months as a course of treatment.\nClinical efficacy  [6]  was assessed and grouped as follows:\na) Recovered: After treatment, the patient’s clinical symptoms completely resolved, the pelvic mass disappeared, and laboratory and ultrasound examinations were normal.\nb) Significant effect: After treatment, the patient’s clinical symptoms disappeared, the pelvic mass decreased by 1/4, and laboratory and ultrasound examinations were normal.\nc) Effective: The patient’s clinical symptoms improved, pelvic mass slightly decreased, and laboratory and ultrasound examinations improved after treatment.\nd) Ineffective: No improvement in clinical symptoms and signs, laboratory tests, or ultrasound examinations.\nTotal effective rate = (recovery + significant effect + effective)/total cases × 100\nSerum sex hormone levels : Changes in E) and FS) levels were assessed in both groups before and after treatment using enzyme-linked immunosorbent assay.\nTumour markers : Serum CA125 and CA199 levels were measured in both groups before and after treatment using chemiluminescence.\nPro-inflammatory cytokines : IL-6, TNF-α, and HSCRP levels were measured in both groups before and after treatment using enzyme-linked immunosorbent assay.\nAdverse reactions  were observed in both groups during the treatment period.\nData were compared between the control and experimental groups using a t-test. All count data were expressed as [n (%)] and compared between the two groups using the two-tailed test. The significance level was set at P<0.05 in the Statistical Package for the Social Sciences software version 21.0.\n\nTable 1  shows that the overall clinical efficacy rate of the patients after treatment (90.74%) was significantly higher than that of the control group (75.93%).\nBefore treatment, there was no statistically significant difference in serum sex hormone levels between the two groups (P>0.05). The E2 and FSH levels in both groups decreased following treatment compared with their pre-treatment levels (P<0.01). These levels were reduced than in the control group (P<0.01).  Table 2\nThe data presented in  Table 3  reveal no difference in the levels of tumour markers between the two groups before treatment (P>0.05). After treatment, the CA125 and CA199 in both groups decreased than before treatment (P<0.01).\nWe found that in the treated groups, IL-6, TNF-α, and HS-CRP levels were reduced than before treatment (P<0.01) ( Table 4 ).\nAn overall incidence of 7.41% (4/54 cases) of adverse reactions was observed in the control group during the treatment period, with three cases of nausea and vomiting and one case of dizziness. A total of 3.70% (2/54 cases) of adverse reactions occurred in the treatment group, including one case of nausea and vomiting and one case of dizziness.\n\nEMs is a common and frequently occurring disease in gynaecology and one of the major factors contributing to infertility in women of childbearing age. The disease has a long course, which can affect the function of the visceral organs, meridians, qi, and blood to varying degrees, aggravate pelvic congestion, hinder the circulation of qi and blood, and seriously affect patients’ quality of life  [7] . Currently, the clinical treatment of EMs involves pharmacotherapy.  Tripterygium  glycosides, derived from the traditional Chinese medicine  Tripterygium wilfordii , exhibit immunosuppressive and anti-inflammatory properties. However, their toxic components have been eliminated in clinical applications. Some studies have demonstrated that  Tripterygium  glycosides can effectively prevent follicular formation by inhibiting the overexpression of inflammatory cytokine IL-6.\nFurthermore, they can inhibit the growth of the ectopic endometrium by suppressing the endometrium in patients  [8] \n [9] . Previous research has confirmed that  Tripterygium  glycosides have advantages over Western medicine in the long-term treatment of Ems  [9] . Gestrinone is a synthetic steroid hormone with anti-pregestational and anti-estrogenic properties. As its primary mechanism of action, it can regulate ovarian endocrine estrogen, promote atrophy and degeneration of the ectopic endometrium, and reduce gonadotropin secretion in the hypothalamic and pituitary axes. This study used Tripterygium glycosides combined with gestrinone to treat patients with EMs. The results indicated that the total clinical efficacy rate after treatment (90.74%) was raised than that in the control group (75.93%; P<0.05), suggesting that the combined medication has improved clinical efficacy and higher safety.\nE2 is secreted by follicular granulosa cells in the ovaries and can promote nerve growth in lesions and increase hyperalgesia in EMs. FSH is a regulatory glycoprotein secreted by the pituitary gland that promotes follicular maturation. E2 is the most potent estrogen secreted by the ovaries and, combined with FSH, promotes follicular development, ovulation, uterine development, and cyclic changes in the endometrium  [10] . Post-treatment E2 and FSH levels were reduced than those in the control group (P<0.05), implying that combining  Tripterygium  glycosides and gestrinone can improve ovarian function in patients. CA125 and CA199 are commonly used in clinical practice to evaluate EM recurrence; elevated levels of these markers are closely associated with disease severity and recurrence  [11] . Some studies have demonstrated that the serum CA125 levels in patients with EMs are higher than in the normal population. This suggests that changes in CA125 levels can be biomarkers to monitor Ems  [12] . The CA125 and CA199 after treatment were reduced than those in the control group (P<0.01), implying that  Tripterygium  glycosides can improve tumour markers in patients and reduce the risk of recurrence.\nIL-6 is a multifunctional inflammatory cytokine that mediates inflammation progression through humoral immunity. Its high expression can increase pelvic and fallopian tube adhesions and fibrosis. TNF-α has multiple biological functions that can initiate and promote the inflammatory immune response. Appropriate levels of TNF-α can regulate ovarian endocrine function in patients, help maintain normal ovulation and regular menstrual cycle, and encourage early embryo implantation and follicular development  [13] . Abnormally elevated TNF-α levels can cause pelvic adhesions, leading to diseases such as miscarriages and infertility. HS-CRP is a common inflammatory and immune regulatory factor significantly increases blood concentration after tissue injury or acute infection. IL-6 promotes HS-CRP secretion, resulting in immune dysfunction and aggravation of inflammatory responses  [14] . Th IL-6, TNF-α, and HS-CRP levels were reduced in the treatment group than in the control group after treatment (P<0.01), implying that  Tripterygium  glycosides could significantly reduce the inflammatory response in patients.\nIn summary,  Tripterygium  glycosides exhibit significant clinical efficacy in treating patients with EMs by significantly improving serum sex hormone levels, reducing tumour marker levels, alleviating inflammatory reactions, and exerting minimal toxic side effects.\n\nThe author(s) assure the readers and the publishers that all data presented here are original.\nJianping Qiu designed and performed the experiments. Ying Xu analyzed and interpreted the data. Fangdan Xu prepared the manuscript with contributions from all co-authors.\nThe authors declare that all data supporting this study’s findings are available within the paper, and any raw data can be obtained from the corresponding author upon request.\nAll the authors declare that they have no conflict of interest in this work.\n\nEMs, Endometriosis;<br>CA125, Cancer antigen 125;<br>CA199, Cancer antigen 199;<br>E2, Estradiol;<br>FSH, Follicle-stimulating hormone;<br>HS-CRP, High-sensitivity C-reactive protein;<br>IL-6, Interleukin-6;<br>TNF-a, Tumour necrosis factor-alpha.","source_license":"CC0","license_restricted":false}