Comparison of the Efficacy and Safety of Mifepristone and Dienogest in the Treatment of Symptomatic Adenomyosis: A Retrospective Cohort Study

Comparison of the Efficacy and Safety of Mifepristone and Dienogest in the Treatment of Symptomatic Adenomyosis: A Retrospective Cohort Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Comparison of the Efficacy and Safety of Mifepristone and Dienogest in the Treatment of Symptomatic Adenomyosis: A Retrospective Cohort Study Yuyan Zhang, Qicai Hu, Minhui Luo, Yaya Yi, Yuhan Lin, Weixia Wei This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8968744/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Objective This study aims to systematically compare the short-term efficacy and safety differences between daily oral 2 mg Dienogest (DNG) and daily oral 10 mg Mifepristone (MIF) in the treatment of patients with symptomatic adenomyosis, focusing on the impact of both drugs on uterine volume, clinical symptoms (dysmenorrhea, menorrhagia), and adverse events, providing a basis for individualized medication treatment. Methods A single-center retrospective cohort study was conducted, including 83 patients diagnosed with adenomyosis who received drug treatment from May 1, 2023, to May 1, 2025. The patients were divided into the Mifepristone group (35 cases, 10 mg/day) and the Dienogest group (48 cases, 2 mg/day), with treatment lasting for 3 months. The uterine volume, endometrial thickness, amenorrhea rate, hemoglobin, CA125 levels, and adverse events were compared between the two groups before and after treatment. Statistical analysis was performed using SPSS 27.0, with P < 0.05 considered statistically significant. Results After 3 months of treatment, the median uterine volume in the MIF group significantly decreased from 151.56 cm³ to 104.07 cm³ (P < 0.01), with a reduction value of 32.29 cm³, significantly higher than the 8.103 cm³ in the DNG group (P < 0.01). The amenorrhea rate in the MIF group (97.1%) was significantly higher than that in the DNG group (58.3%). Both groups showed a significant increase in hemoglobin and a significant decrease in CA125 (both P < 0.01). The DNG group showed a significant thinning of endometrial thickness (P 0.05). The overall adverse reaction rate in the MIF group (45.71%) was lower than that in the DNG group (75%). Conclusion In a 3-month pre-treatment period, Mifepristone significantly outperformed Dienogest in reducing uterine volume and improving the amenorrhea rate in patients with adenomyosis, while also exhibiting better tolerance. Adenomyosis Mifepristone Dienogest Uterine volume Efficacy Safety Introduction Adenomyosis is a common estrogen-dependent benign disease in women of childbearing age, characterized pathologically by the invasion of endometrial glands and stroma into the myometrium, accompanied by hyperplasia and hypertrophy of surrounding muscle layers[ 1 ]. Epidemiological studies indicate that its prevalence in women of reproductive age can reach 20%–30%, making it a significant cause of progressively worsening dysmenorrhea, menorrhagia, chronic pelvic pain, anemia, and infertility, greatly impairing the quality of life and physical and mental health of patients[ 2 , 3 ]. For patients wishing to retain their uterus, medical treatment is the first-line option for symptom control and disease progression delay[ 4 ]. Common clinical regimens include gonadotropin-releasing hormone agonists (GnRH-a), combined short-acting oral contraceptives, and the levonorgestrel intrauterine release system (LNG-IUS, Mirena)[ 5 ]. Among these, oral medications like Mifepristone and Dienogest are increasingly valued in clinical management for their convenience and reversibility, although their mechanisms of action and treatment focuses differ. Mifepristone is a classic progesterone receptor antagonist that works by competitively binding to progesterone receptors, inhibiting the hypothalamic-pituitary-ovarian axis function, and lowering estrogen levels, thereby inducing atrophy of ectopic endometrium. Traditionally, Mifepristone has been used in high doses to terminate early pregnancies, but in recent years, more studies have begun to focus on the potential of low-dose (5–25 mg/day) Mifepristone in treating gynecological diseases such as uterine fibroids, endometriosis, and adenomyosis[ 6 , 7 ]. Recent literature has indicated that low-dose Mifepristone can effectively alleviate pain associated with adenomyosis, reduce menstrual flow, and may shrink uterine volume, although its application in adenomyosis remains in the evidence accumulation stage[ 8 ]. Dienogest, on the other hand, is a highly selective progestin with strong anti-proliferative and anti-inflammatory effects on the endometrium and a central ovulation-inhibiting effect, which can effectively relieve pain and abnormal uterine bleeding by directly inducing apoptosis in ectopic endometrial cells[ 9 ]. However, clinical observations have also suggested that its effect on reducing overall uterine volume may be limited[ 10 ]. Currently, Dienogest has become a commonly used choice for long-term medical management of adenomyosis, but direct comparative studies between Dienogest and Mifepristone regarding uterine contraction efficacy are still insufficient. In summary, while both Mifepristone and Dienogest can be used for the medical treatment of adenomyosis, their mechanisms of action differ significantly, and there may be differences in their advantages and disadvantages regarding efficacy and safety. Therefore, this study aims to compare the effects of the two drugs on uterine volume reduction, amenorrhea rates, improvements in hemoglobin and CA125 levels, and safety differences in patients with adenomyosis through retrospective cohort analysis, with the goal of providing evidence-based guidance for individualized medication based on different treatment objectives in clinical practice. Clinical Data and Methods General Data This study adopts a single-center, retrospective cohort study design. Retrospective data was collected from patients diagnosed with uterine adenomyosis at Peking University Shenzhen Hospital between May 1, 2023, and May 1, 2025, who received 10mg mifepristone or 2mg dienogest monotherapy for 3 months. All patients were followed up by phone and outpatient visits at the 3rd month after treatment. This study was approved by the Peking University Shenzhen Hospital's medical ethics committee (Approval No: Peking University Shenzhen Hospital Institutional Review Board (Research) [2025] No. (323)), and all patient data were anonymized to protect patient privacy. 1.2 Inclusion and Exclusion Criteria Inclusion criteria: (1)Confirmed diagnosis of adenomyosis based on clinical symptoms, gynecological examination, and transvaginal ultrasound (or MRI). (2)Women of childbearing age or perimenopausal women aged 25 to 50. (3)No concurrent use of other hormonal medications during treatment. (4) Complete clinical data and imaging examination records available both before and after 3 months of treatment. Exclusion criteria: (1)Contraindications to the use of Mifepristone or Dienogest. (2)Abnormal uterine bleeding without excluding endometrial pathologies. (3)Presence of other serious internal or surgical diseases.(4) History of malignant tumors.(5)Recurrence after surgical treatment for adenomyosis.(6)Pregnancy, breastfeeding, or recent (within 6 months) plans for childbirth.(7) Incomplete clinical data or follow-up records. Based on the above criteria, a total of 83 eligible patients were screened. According to their treatment regimens, they were divided into the Mifepristone group (MIF group, n = 35) and the Dienogest group (DNG group, n = 48). 1.3 Data Extraction and Outcome Observation Indicators The following data were collected through the hospital electronic medical record system: 1.3.1 Baseline Data Baseline variables included the basic information of selected patients, such as age, height, weight, and uterine volume before treatment. 1.3.2 Primary Outcome Indicators Uterine Volume (UV): All patients underwent transvaginal color Doppler ultrasound examinations before treatment and 3 months after treatment. Experienced ultrasound physicians measured the longitudinal diameter (L), anteroposterior diameter (AP), and transverse diameter (T) of the uterus. Uterine volume was calculated using the ellipsoid formula: UV (cm³) = L (cm) × AP (cm) × T (cm) × 0.52. 1.3.3 Secondary Outcome Indicators Endometrial Thickness: Measured through transvaginal ultrasound as the double-layer endometrial thickness. 2) Amenorrhea Rate: The proportion of patients who experienced amenorrhea (defined as no vaginal bleeding for more than 60 consecutive days) within 3 months of treatment was recorded. 3) Laboratory Indicators: Pre-treatment and post-treatment blood routine examination results were collected to record hemoglobin (Hb) levels; serum tumor marker examination results were collected to record cancer antigen 125 (CA125) levels. 1.3.4 Safety Indicators: Adverse Events (AEs): All adverse events reported by patients during treatment or discovered through doctor inquiries were detailed and classified, including irregular vaginal bleeding, breast tenderness, nausea, and abnormal liver and kidney function. The incidence of adverse reactions was statistically analyzed to assess the safety of different regimens. 1.4 Statistical Methods Statistical analysis was performed using SPSS 27.0 software. For metric data, if the sample size was greater than 50, the Kolmogorov-Smirnov test was used; otherwise, the Shapiro-Wilk test was used. Normally distributed data were reported as ± s and analyzed using t-tests; skewed distributions were reported as M(P25,P75) and analyzed using the non-parametric Mann-Whitney U test. A P value of < 0.05 was considered statistically significant. Results 2.1 Baseline Data of Patients There were no statistically significant differences between the two groups in age, height, weight, and uterine volume before treatment (P > 0.05), indicating comparability (Table 1 ). Table 1 Baseline Data of Included Patients General Information MIF Group (n = 35) DNG Group (n = 48) t or Z P Age (± s, years) 40.69 ± 7.65 37.83 ± 5.44 -1.886 0.064 Height (± s, cm) 158.11 ± 4.81 159.31 ± 5.03 1.091 0.278 Weight (± s, kg) 57.81 ± 5.62 55.77 ± 5.06 -1.732 0.087 Uterine Volume Before Treatment [M(P25,P75)] 151.56(130.9,161.5) 133.268(127.5,143,6) -1.595 0.111 2.2 Primary Outcome Indicators After 3 months of treatment, significant differences in uterine volume changes were observed between the two groups (Table 2 ). Intra-group comparison: The uterine volume in the MIF group significantly decreased from a median of 151.557 cm³ before treatment to 104.067 cm³ after treatment, with a median reduction of 32.287 cm³, corresponding to a reduction rate of approximately 21.3%. The differences before and after within the group are statistically significant (P < 0.01). However, the change in uterine volume in the DNG group was not obvious, decreasing from a median of 133.268 cm³ before treatment to 127.332 cm³ after treatment, with a median reduction of only 8.103 cm³, corresponding to a reduction rate of approximately 6.0%. The differences before and after within the group are statistically significant (P < 0.01). Inter-group comparison: Three months after treatment, the uterine volume in the MIF group was significantly smaller than that in the DNG group (P < 0.01). More importantly, the median reduction in uterine volume in the MIF group (32.287 cm³) was significantly greater than that in the DNG group (8.103 cm³), with a highly statistically significant difference between the groups (P < 0.01). These results strongly indicate that in the short term, 10 mg mifepristone is far more effective than 2 mg dienogest in reducing the volume of adenomyosis lesions. Table 2 Uterine Volume Changes Before and After Treatment in Both Groups [M(P25,P75)] Group Uterine Volume (cm³) Before Treatment After Treatment Within-group Difference Z P MIF Group 151.557(131.4,160.5) 104.067(80.3,132.6) 32.287(14.6,49.0) 4.259 <0.01 DNG Group 133.268(127.6,142.2) 127.332(106.3,145.7) 8.103(-5.2,24.8) 2.780 <0.01 Z -1.595 -2.886 -3.553 P 0.111 < 0.01 <0.01 2.3.1 Endometrial Thickness There were inter-group differences in the changes of endometrial thickness before and after treatment. The change in endometrial thickness in the MIF group was not significant (P > 0.05), while the endometrial thickness in the DNG group significantly decreased (P < 0.01). After treatment, the comparison between groups showed that the endometrial thickness in the DNG group was significantly thinner than that in the MIF group (P < 0.01). (Table 3 ) Table 3 Endometrial Thickness Before and After Treatment in Two Groups of Patients [ \(\stackrel{-}{\mathbf{x}}\) ±s] Group Endometrial Thickness (cm) Before Treatment After Treatment t P MIF Group 6.37 ± 2.86 6.78 ± 3.30 -0.687 0.497 DNG group 5.23 ± 2.32 3.93 ± 1.79 4.807 <0.01 t -2.131 -4.993 P 0.037 < 0.01 2.3.2 Hemoglobin and CA125 Levels The hemoglobin levels in both groups of patients significantly increased after treatment compared to before treatment (P 0.05). The serum CA125 levels in both groups significantly decreased after treatment compared to before treatment (P < 0.01). (Tables 4 and 5 ) Table 4 Hemoglobin and CA125 Levels Before and After Treatment in Two Groups of Patients [M(P25,P75)] Group Hemoglobin (g/L) Before Treatment After Treatment Z P MIF Group 110(95.5,127.5) 132(123.5,138.0) 5.128 <0.01 DNG Group 123.5(115.0,130.0) 135(126.0,138.3) -5.521 <0.01 Z -2.491 -0.982 P 0.013 0.353 Table 5 CA125 Levels Before and After Treatment in Two Groups of Patients [M(P25,P75)] Group CA125 U/mL Before Treatment After Treatment Z P MIF Group 116.500(46.3,154.5) 50.600(35.6,103.0) 4.406 <0.01 DNG Group 37.6(17.7,85.2) 24.2(14.0,37.9) 5.164 <0.01 Z -4.489 -4.906 P < 0.01 < 0.01 2.3.3 Amenorrhea Rate and Adverse Reactions Amenorrhea Rate: After 3 months of treatment, the amenorrhea rate in the MIF group was 97.1% (34/35), significantly higher than the 58.3% (28/48) in the DNG group. Adverse Reactions: The overall incidence of adverse reactions in the MIF group was 45.71% (16/35), significantly lower than the 75% (36/48) in the DNG group. (Table 6 ) Table 6 Adverse Reactions in Two Groups of Patients (%) Adverse Reaction Number of Patients (%) MIF Group (n = 35) DNG Group (n = 48) Headache 2(5.71) 4(8.33) Insomnia 2(5.71) 5(10.42) Hot Flashes 2(5.71) 5(10.42) Weight Gain 4(11.42) 8(16.67) Breast Tenderness 2(5.71) 6(12.50) Irritability 3(8.57) 6(12.50) Increased Vaginal Discharge 1(2.86) 2(4.17) Adverse Reaction Rate 16(45.71) 36(75.00) Discussion This study conducted a retrospective cohort analysis comparing the differences between mifepristone and dienogest in improving uterine volume reduction, amenorrhea rate, hemoglobin, and CA125 levels in patients with adenomyosis, as well as the adverse drug reactions. The results showed that the mifepristone group significantly outperformed the dienogest group in reducing uterine volume, had a higher amenorrhea rate, and a lower incidence of adverse reactions, providing a basis for clinical medication selection. 3.1 Possible Mechanism Differences in Uterine Volume Reduction The most striking result of this study is the huge difference in the effectiveness of the two drugs in reducing uterine volume. The MIF group achieved over a 20% reduction in uterine volume within just three months, while the DNG group's volume changes were not significant. This difference is deeply rooted in their distinctly different pharmacological mechanisms of action. Mifepristone, as a progesterone receptor antagonist, competitively binds to the progesterone receptor, not only inhibiting the proliferation of endometrial and ectopic endometrial cells and inducing their apoptosis but also possibly creating an unfavorable microenvironment for the survival of adenomyosis lesions by regulating local estrogen receptor expression, thus achieving significant uterine volume reduction[ 8 , 9 ]. The results of this study showed that the median uterine volume in the mifepristone group decreased from 151.56 cm³ to 104.07 cm³, with a significant difference within the group (P < 0.01), which is consistent with a recent prospective study confirming that a low dose of mifepristone (10 mg/day) can effectively reduce uterine volume in patients with adenomyosis after three months of treatment[ 8 ]. In contrast, dienogest, as a highly selective progestin, while capable of alleviating pain and reducing menstrual flow through ovulation suppression and direct anti-inflammatory effects, may have a weaker role in promoting the apoptosis of ectopic endometrial cells and reducing overall uterine volume[ 10 , 11 ]. The slight change in uterine volume in the dienogest group in this study further supports the view that its effect on uterine reduction is limited, possibly related to its primary action on the endometrium rather than the myometrial lesions[ 10 ]. Therefore, dienogest may primarily relieve symptoms in the short term by suppressing inflammation and bleeding, while its effect on reducing uterine volume may require a longer treatment duration (e.g., six months or more) to manifest. The lack of significant change in uterine volume in the DNG group within three months aligns with this inference. 3.2 Differences in Amenorrhea Rate and Endometrial Response In this study, the amenorrhea rate in the mifepristone group reached 97.1%, significantly higher than that in the dienogest group (58.3%). This high amenorrhea rate is closely related to mifepristone's potent antagonism of progesterone receptors and deep suppression of endometrial function. Conversely, although dienogest significantly caused endometrial atrophy (the study showed a reduction from 5.23 cm to 3.93 cm, P < 0.01), its resulting amenorrhea rate was relatively low, possibly related to its higher incidence of breakthrough bleeding, which is consistent with reports of irregular bleeding during the early treatment phase of dienogest[ 12 ]. However, despite the high amenorrhea rate in the mifepristone group, the endometrial thickness in the mifepristone group showed a slight increasing trend post-treatment (from 6.37 ± 2.86mm to 6.78 ± 3.30mm, P > 0.05), while the dienogest group showed the expected significant thinning (from 5.23 ± 2.32mm to 3.93 ± 1.79mm, P < 0.01). This may relate to the “non-antagonistic estrogen effect” caused by the progesterone receptor antagonism. By blocking the progesterone receptor, mifepristone relieves the normal antagonistic effect of progesterone on estrogen-induced endometrial proliferation. In the presence of ongoing estrogen secretion from the ovaries (albeit possibly at lower levels), the endometrium may exhibit a certain proliferative response or may be difficult to atrophy under continuous, non-antagonistic stimulation by estrogen[ 13 ]. 3.3 Improvement in Hemoglobin and CA125 Levels Both groups of patients showed a significant increase in hemoglobin after treatment (P < 0.01), and CA125 levels also significantly decreased (P < 0.01), indicating that both drugs can effectively improve anemic conditions and suppress disease activity. CA125, a commonly used serum marker reflecting the severity of endometriotic disease, often shows a decline in levels associated with reduced lesion activity and symptom improvement[ 14 , 15 ]. Although the differences between groups were not significant, the baseline CA125 level in the mifepristone group was higher, and the post-treatment decrease was notable, suggesting its better inhibitory effect on more active or widespread lesions, which warrants further investigation in future larger sample studies. 3.4 Comparison of Adverse Reactions In this study, the overall incidence of adverse reactions in the mifepristone group (45.71%) was lower than that in the dienogest group (75%). The dienogest group reported higher rates of adverse reactions such as hot flashes, breast tenderness, irritability, and weight gain, which may be related to its feedback inhibition on the hypothalamic-pituitary axis and stronger progestogenic activity, consistent with literature reports[ 12 ]. In contrast, the adverse reaction profile of mifepristone was relatively mild, and patient tolerance was good; a six-month safety study also reported no severe liver or kidney function abnormalities, supporting its safety for short-term use[ 16 ]. This provides a reference for clinicians to personalize medication selection based on patients' sensitivity to side effects. 3.5 Limitations of the Study This study is a single-center retrospective design with a small sample size (n = 84) and a short follow-up period (3 months), which may impact the generalizability of the results and the assessment of long-term efficacy (e.g., symptom recurrence, uterine volume rebound). Moreover, although the measurement of uterine volume used a standardized formula, it may still be subject to the subjectivity of the ultrasound operator. Future studies need to conduct multi-center, large-sample, long-term follow-up prospective randomized controlled trials and consider including quality of life scores and other patient-reported outcomes to provide higher levels of evidence. Clinical Significance and Prospects This study suggests that for patients with adenomyosis who plan to place a Mirena IUD in a short time and require rapid pre-reduction of uterine volume to facilitate placement and enhance efficacy, mifepristone may be a superior pre-treatment medication choice compared to dienogest. Its rapid uterine reduction, high amenorrhea rate, and good tolerance make it of significant value in clinical practice. However, for patients needing long-term medication management for adenomyosis, long-term control of pain and reduction of menstrual flow symptoms are better suited for dienogest, as confirmed by many studies. Future research could further explore the long-term effects of the two drugs on ovarian function and fertility preservation, as well as optimize strategies for combination therapy (e.g., sequential therapy) to establish a more refined medication management pathway for adenomyosis. Conclusion In summary, the results of this retrospective cohort study indicate that in a short-term treatment period of three months, oral administration of 10 mg mifepristone daily shows significant superiority over daily administration of 2 mg dienogest in effectively reducing uterine volume in patients with adenomyosis, with a lower overall incidence of adverse reactions and better patient tolerance. Although both drugs are comparable in alleviating core symptoms such as dysmenorrhea and reducing menstrual flow, the dual advantage of mifepristone in improving uterine structure and enhancing safety makes it a highly potential new individualized treatment option particularly suited for patients with adenomyosis whose primary treatment goal is to reduce an enlarged uterus. Future large-scale prospective randomized controlled studies will further confirm these findings and provide more solid evidence for the application of mifepristone in the long-term management of adenomyosis. Abbreviations DNG Dienogest MIF Mifepristone GnRH-a Gonadotropin-releasing hormone agonist LNG-IUS Levonorgestrel-releasing intrauterine system UV Uterine volume Hb Hemoglobin CA125 Cancer antigen 125 AE Adverse event MRI Magnetic resonance imaging IUD Intrauterine device. Declarations Ethics approval and consent to participate This study was approved by the Medical Ethics Committee of Peking University Shenzhen Hospital (Approval No: Peking University Shenzhen Hospital Institutional Review Board (Research) 2025 No. (323)). All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Written informed consent was obtained from all individual participants included in the study. Consent for publication Not applicable. Competing Interests The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Funding The author(s) declare that no financial support was received for the research, authorship, and/or publication of this article. Author Contribution YZ and QH contributed to conception and design of the study. YZ wrote the draft of the manuscript. ML, YY, and YL organized the database and performed data collection. WW supervised the project. All authors contributed to manuscript revision, read, and approved the submitted version. Acknowledgements Not applicable. Data Availability The datasets generated and analyzed during the current study are not publicly available due to privacy and ethical restrictions but are available from the corresponding author on reasonable request. References Bird CC, McElin TW, Manalo-Estrella P. The elusive adenomyosis of the uterus–revisited. Am J Obstet Gynecol. 1972;112(5):583–93. Struble J, Reid S, Bedaiwy MA. Adenomyosis: A Clinical Review of a Challenging Gynecologic Condition. J Minim Invasive Gynecol. 2016;23(2):164–85. Choi EJ, Cho SB, Lee SR, Lim YM, Jeong K, Moon HS, Chung H. Comorbidity of gynecological and non-gynecological diseases with adenomyosis and endometriosis. 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F1000Res 2019, 8. Benetti-Pinto CL, Mira TAA, Yela DA, Teatin-Juliato CR, Brito LGO. Pharmacological Treatment for Symptomatic Adenomyosis: A Systematic Review. Rev Bras Ginecol Obstet. 2019;41(9):564–74. Fu J, Song H, Zhou M, Zhu H, Wang Y, Chen H, Huang W. Progesterone receptor modulators for endometriosis. Cochrane Database Syst Rev. 2017;7(7):Cd009881. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8968744","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":603860954,"identity":"949c22e1-4fa4-4e27-a321-8e9022483ed7","order_by":0,"name":"Yuyan Zhang","email":"","orcid":"","institution":"Peking University Shenzhen Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yuyan","middleName":"","lastName":"Zhang","suffix":""},{"id":603860955,"identity":"4a23e09a-a048-46c1-b7d9-adc9e89317f5","order_by":1,"name":"Qicai Hu","email":"","orcid":"","institution":"Peking University Shenzhen Hospital","correspondingAuthor":false,"prefix":"","firstName":"Qicai","middleName":"","lastName":"Hu","suffix":""},{"id":603860956,"identity":"3d7e0fb3-91da-4c5e-8f6c-3154c7c60865","order_by":2,"name":"Minhui Luo","email":"","orcid":"","institution":"Peking University Shenzhen Hospital","correspondingAuthor":false,"prefix":"","firstName":"Minhui","middleName":"","lastName":"Luo","suffix":""},{"id":603860957,"identity":"95a08171-a6d5-46a5-bfec-ec8857ae43a7","order_by":3,"name":"Yaya Yi","email":"","orcid":"","institution":"Peking University Shenzhen Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yaya","middleName":"","lastName":"Yi","suffix":""},{"id":603860958,"identity":"b10d73ab-db33-474e-aa86-8a7a0bbaed71","order_by":4,"name":"Yuhan Lin","email":"","orcid":"","institution":"Peking University Shenzhen Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yuhan","middleName":"","lastName":"Lin","suffix":""},{"id":603860959,"identity":"ece8e99b-90ec-491f-85af-4a94c59d892e","order_by":5,"name":"Weixia Wei","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA4klEQVRIie2PMQrCQBBFJwSSZsF2QsAzjCyIhZCrZJtUKoKNhejKQmw8QI7hFWTRNDlAOpWAtaWFqNvYblJa7Cs+U8ybzwA4HH+JJ00g9HxPXR807ndXop3KB8U8493LqCplzB5atG+WKo/ZcgRQC8nH5KcQ6tPBfvyoOKsQvELIZkLBDFiW1TZlWIttM80RfDQtE2ILQDa0K5eb1NM3QmCUeEQmW5XaMy0SgbGjjIGoXUkqofjrjIDhNh/sKeVB2y/RrrxHxWoNiQ6b6/P16fdCfbYqPzbyNwVd1h0Oh8Nh5wsWNkk4FSfbzwAAAABJRU5ErkJggg==","orcid":"","institution":"Peking University Shenzhen Hospital","correspondingAuthor":true,"prefix":"","firstName":"Weixia","middleName":"","lastName":"Wei","suffix":""}],"badges":[],"createdAt":"2026-02-25 14:23:16","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8968744/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8968744/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":106402839,"identity":"66bad1fe-2c32-4f39-9796-01b0d222d246","added_by":"auto","created_at":"2026-04-08 09:13:00","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":936788,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8968744/v1/72ccbcff-9bcd-40b6-b003-17f6bf62fdaf.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Comparison of the Efficacy and Safety of Mifepristone and Dienogest in the Treatment of Symptomatic Adenomyosis: A Retrospective Cohort Study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAdenomyosis is a common estrogen-dependent benign disease in women of childbearing age, characterized pathologically by the invasion of endometrial glands and stroma into the myometrium, accompanied by hyperplasia and hypertrophy of surrounding muscle layers[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Epidemiological studies indicate that its prevalence in women of reproductive age can reach 20%\u0026ndash;30%, making it a significant cause of progressively worsening dysmenorrhea, menorrhagia, chronic pelvic pain, anemia, and infertility, greatly impairing the quality of life and physical and mental health of patients[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eFor patients wishing to retain their uterus, medical treatment is the first-line option for symptom control and disease progression delay[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Common clinical regimens include gonadotropin-releasing hormone agonists (GnRH-a), combined short-acting oral contraceptives, and the levonorgestrel intrauterine release system (LNG-IUS, Mirena)[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Among these, oral medications like Mifepristone and Dienogest are increasingly valued in clinical management for their convenience and reversibility, although their mechanisms of action and treatment focuses differ.\u003c/p\u003e \u003cp\u003eMifepristone is a classic progesterone receptor antagonist that works by competitively binding to progesterone receptors, inhibiting the hypothalamic-pituitary-ovarian axis function, and lowering estrogen levels, thereby inducing atrophy of ectopic endometrium. Traditionally, Mifepristone has been used in high doses to terminate early pregnancies, but in recent years, more studies have begun to focus on the potential of low-dose (5\u0026ndash;25 mg/day) Mifepristone in treating gynecological diseases such as uterine fibroids, endometriosis, and adenomyosis[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Recent literature has indicated that low-dose Mifepristone can effectively alleviate pain associated with adenomyosis, reduce menstrual flow, and may shrink uterine volume, although its application in adenomyosis remains in the evidence accumulation stage[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eDienogest, on the other hand, is a highly selective progestin with strong anti-proliferative and anti-inflammatory effects on the endometrium and a central ovulation-inhibiting effect, which can effectively relieve pain and abnormal uterine bleeding by directly inducing apoptosis in ectopic endometrial cells[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. However, clinical observations have also suggested that its effect on reducing overall uterine volume may be limited[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Currently, Dienogest has become a commonly used choice for long-term medical management of adenomyosis, but direct comparative studies between Dienogest and Mifepristone regarding uterine contraction efficacy are still insufficient.\u003c/p\u003e \u003cp\u003eIn summary, while both Mifepristone and Dienogest can be used for the medical treatment of adenomyosis, their mechanisms of action differ significantly, and there may be differences in their advantages and disadvantages regarding efficacy and safety. Therefore, this study aims to compare the effects of the two drugs on uterine volume reduction, amenorrhea rates, improvements in hemoglobin and CA125 levels, and safety differences in patients with adenomyosis through retrospective cohort analysis, with the goal of providing evidence-based guidance for individualized medication based on different treatment objectives in clinical practice.\u003c/p\u003e"},{"header":"Clinical Data and Methods","content":"\u003cp\u003e \u003col\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eGeneral Data\u003c/b\u003e \u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003c/ol\u003e \u003c/p\u003e \u003cp\u003eThis study adopts a single-center, retrospective cohort study design. Retrospective data was collected from patients diagnosed with uterine adenomyosis at Peking University Shenzhen Hospital between May 1, 2023, and May 1, 2025, who received 10mg mifepristone or 2mg dienogest monotherapy for 3 months. All patients were followed up by phone and outpatient visits at the 3rd month after treatment. This study was approved by the Peking University Shenzhen Hospital's medical ethics committee (Approval No: Peking University Shenzhen Hospital Institutional Review Board (Research) [2025] No. (323)), and all patient data were anonymized to protect patient privacy.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e1.2 Inclusion and Exclusion Criteria\u003c/h2\u003e \u003cp\u003eInclusion criteria: (1)Confirmed diagnosis of adenomyosis based on clinical symptoms, gynecological examination, and transvaginal ultrasound (or MRI). (2)Women of childbearing age or perimenopausal women aged 25 to 50. (3)No concurrent use of other hormonal medications during treatment. (4) Complete clinical data and imaging examination records available both before and after 3 months of treatment.\u003c/p\u003e \u003cp\u003eExclusion criteria: (1)Contraindications to the use of Mifepristone or Dienogest. (2)Abnormal uterine bleeding without excluding endometrial pathologies. (3)Presence of other serious internal or surgical diseases.(4) History of malignant tumors.(5)Recurrence after surgical treatment for adenomyosis.(6)Pregnancy, breastfeeding, or recent (within 6 months) plans for childbirth.(7) Incomplete clinical data or follow-up records.\u003c/p\u003e \u003cp\u003eBased on the above criteria, a total of 83 eligible patients were screened. According to their treatment regimens, they were divided into the Mifepristone group (MIF group, n\u0026thinsp;=\u0026thinsp;35) and the Dienogest group (DNG group, n\u0026thinsp;=\u0026thinsp;48).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e1.3 Data Extraction and Outcome Observation Indicators\u003c/h2\u003e \u003cp\u003eThe following data were collected through the hospital electronic medical record system:\u003c/p\u003e \u003cdiv id=\"Sec5\" class=\"Section3\"\u003e \u003ch2\u003e1.3.1 Baseline Data\u003c/h2\u003e \u003cp\u003eBaseline variables included the basic information of selected patients, such as age, height, weight, and uterine volume before treatment.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section3\"\u003e \u003ch2\u003e1.3.2 Primary Outcome Indicators\u003c/h2\u003e \u003cp\u003eUterine Volume (UV): All patients underwent transvaginal color Doppler ultrasound examinations before treatment and 3 months after treatment. Experienced ultrasound physicians measured the longitudinal diameter (L), anteroposterior diameter (AP), and transverse diameter (T) of the uterus. Uterine volume was calculated using the ellipsoid formula: UV (cm\u0026sup3;)\u0026thinsp;=\u0026thinsp;L (cm) \u0026times; AP (cm) \u0026times; T (cm) \u0026times; 0.52.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section3\"\u003e \u003ch2\u003e1.3.3 Secondary Outcome Indicators\u003c/h2\u003e \u003cp\u003eEndometrial Thickness: Measured through transvaginal ultrasound as the double-layer endometrial thickness. 2) Amenorrhea Rate: The proportion of patients who experienced amenorrhea (defined as no vaginal bleeding for more than 60 consecutive days) within 3 months of treatment was recorded. 3) Laboratory Indicators: Pre-treatment and post-treatment blood routine examination results were collected to record hemoglobin (Hb) levels; serum tumor marker examination results were collected to record cancer antigen 125 (CA125) levels.\u003c/p\u003e \u003cp\u003e1.3.4 Safety Indicators: Adverse Events (AEs): All adverse events reported by patients during treatment or discovered through doctor inquiries were detailed and classified, including irregular vaginal bleeding, breast tenderness, nausea, and abnormal liver and kidney function. The incidence of adverse reactions was statistically analyzed to assess the safety of different regimens.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003e1.4 Statistical Methods\u003c/h2\u003e \u003cp\u003eStatistical analysis was performed using SPSS 27.0 software. For metric data, if the sample size was greater than 50, the Kolmogorov-Smirnov test was used; otherwise, the Shapiro-Wilk test was used. Normally distributed data were reported as \u0026plusmn;\u0026thinsp;s and analyzed using t-tests; skewed distributions were reported as M(P25,P75) and analyzed using the non-parametric Mann-Whitney U test. A P value of \u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Baseline Data of Patients\u003c/h2\u003e \u003cp\u003eThere were no statistically significant differences between the two groups in age, height, weight, and uterine volume before treatment (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05), indicating comparability (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline Data of Included Patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGeneral Information\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMIF Group (n\u0026thinsp;=\u0026thinsp;35)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDNG Group (n\u0026thinsp;=\u0026thinsp;48)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003et or Z\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (\u0026plusmn;\u0026thinsp;s, years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e40.69\u0026thinsp;\u0026plusmn;\u0026thinsp;7.65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e37.83\u0026thinsp;\u0026plusmn;\u0026thinsp;5.44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e-1.886\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.064\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHeight (\u0026plusmn;\u0026thinsp;s, cm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e158.11\u0026thinsp;\u0026plusmn;\u0026thinsp;4.81\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e159.31\u0026thinsp;\u0026plusmn;\u0026thinsp;5.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.091\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.278\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWeight (\u0026plusmn;\u0026thinsp;s, kg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e57.81\u0026thinsp;\u0026plusmn;\u0026thinsp;5.62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e55.77\u0026thinsp;\u0026plusmn;\u0026thinsp;5.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e-1.732\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.087\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUterine Volume Before Treatment [M(P25,P75)]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e151.56(130.9,161.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e133.268(127.5,143,6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e-1.595\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.111\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Primary Outcome Indicators\u003c/h2\u003e \u003cp\u003eAfter 3 months of treatment, significant differences in uterine volume changes were observed between the two groups (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIntra-group comparison: The uterine volume in the MIF group significantly decreased from a median of 151.557 cm\u0026sup3; before treatment to 104.067 cm\u0026sup3; after treatment, with a median reduction of 32.287 cm\u0026sup3;, corresponding to a reduction rate of approximately 21.3%. The differences before and after within the group are statistically significant (P\u0026thinsp;\u0026lt;\u0026thinsp;0.01). However, the change in uterine volume in the DNG group was not obvious, decreasing from a median of 133.268 cm\u0026sup3; before treatment to 127.332 cm\u0026sup3; after treatment, with a median reduction of only 8.103 cm\u0026sup3;, corresponding to a reduction rate of approximately 6.0%. The differences before and after within the group are statistically significant (P\u0026thinsp;\u0026lt;\u0026thinsp;0.01).\u003c/p\u003e \u003cp\u003eInter-group comparison: Three months after treatment, the uterine volume in the MIF group was significantly smaller than that in the DNG group (P\u0026thinsp;\u0026lt;\u0026thinsp;0.01). More importantly, the median reduction in uterine volume in the MIF group (32.287 cm\u0026sup3;) was significantly greater than that in the DNG group (8.103 cm\u0026sup3;), with a highly statistically significant difference between the groups (P\u0026thinsp;\u0026lt;\u0026thinsp;0.01). These results strongly indicate that in the short term, 10 mg mifepristone is far more effective than 2 mg dienogest in reducing the volume of adenomyosis lesions.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eUterine Volume Changes Before and After Treatment in Both Groups [M(P25,P75)]\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eGroup\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"6\" nameend=\"c7\" namest=\"c2\"\u003e \u003cp\u003eUterine Volume (cm\u0026sup3;)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBefore Treatment\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c6\" namest=\"c3\"\u003e \u003cp\u003eAfter Treatment Within-group Difference\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eZ P\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMIF Group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e151.557(131.4,160.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c5\" namest=\"c3\"\u003e \u003cp\u003e104.067(80.3,132.6) 32.287(14.6,49.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e4.259 \u0026lt;0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDNG Group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e133.268(127.6,142.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e127.332(106.3,145.7) 8.103(-5.2,24.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e \u003cp\u003e2.780 \u0026lt;0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eZ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-1.595\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-2.886 -3.553\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c7\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.111\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.01 \u0026lt;0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c7\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cdiv id=\"Sec12\" class=\"Section3\"\u003e \u003ch2\u003e2.3.1 Endometrial Thickness\u003c/h2\u003e \u003cp\u003eThere were inter-group differences in the changes of endometrial thickness before and after treatment. The change in endometrial thickness in the MIF group was not significant (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05), while the endometrial thickness in the DNG group significantly decreased (P\u0026thinsp;\u0026lt;\u0026thinsp;0.01). After treatment, the comparison between groups showed that the endometrial thickness in the DNG group was significantly thinner than that in the MIF group (P\u0026thinsp;\u0026lt;\u0026thinsp;0.01). (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eEndometrial Thickness Before and After Treatment in Two Groups of Patients [\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\stackrel{-}{\\mathbf{x}}\\)\u003c/span\u003e\u003c/span\u003e\u0026plusmn;s]\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eGroup\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"6\" nameend=\"c7\" namest=\"c2\"\u003e \u003cp\u003eEndometrial Thickness (cm)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBefore Treatment\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003eAfter Treatment t P\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMIF Group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.37\u0026thinsp;\u0026plusmn;\u0026thinsp;2.86\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c6\" namest=\"c3\"\u003e \u003cp\u003e6.78\u0026thinsp;\u0026plusmn;\u0026thinsp;3.30 -0.687 0.497\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDNG group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.23\u0026thinsp;\u0026plusmn;\u0026thinsp;2.32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c5\" namest=\"c3\"\u003e \u003cp\u003e3.93\u0026thinsp;\u0026plusmn;\u0026thinsp;1.79 4.807 \u0026lt;0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003et\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-2.131\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-4.993\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c7\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.037\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c7\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section3\"\u003e \u003ch2\u003e2.3.2 Hemoglobin and CA125 Levels\u003c/h2\u003e \u003cp\u003eThe hemoglobin levels in both groups of patients significantly increased after treatment compared to before treatment (P\u0026thinsp;\u0026lt;\u0026thinsp;0.01), but there was no significant difference in levels between groups after treatment (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05). The serum CA125 levels in both groups significantly decreased after treatment compared to before treatment (P\u0026thinsp;\u0026lt;\u0026thinsp;0.01). (Tables\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e and \u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eHemoglobin and CA125 Levels Before and After Treatment in Two Groups of Patients [M(P25,P75)]\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eGroup\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e \u003cp\u003eHemoglobin (g/L)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBefore Treatment\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003eAfter Treatment Z P\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"1\" nameend=\"c5\" namest=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMIF Group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e110(95.5,127.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e132(123.5,138.0) 5.128 \u0026lt;0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDNG Group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e123.5(115.0,130.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e135(126.0,138.3) -5.521 \u0026lt;0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eZ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-2.491\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.982\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.013\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.353\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCA125 Levels Before and After Treatment in Two Groups of Patients [M(P25,P75)]\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eGroup\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e \u003cp\u003eCA125 U/mL\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBefore Treatment\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003eAfter Treatment Z P\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"1\" nameend=\"c5\" namest=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMIF Group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e116.500(46.3,154.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e50.600(35.6,103.0) 4.406 \u0026lt;0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDNG Group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e37.6(17.7,85.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e24.2(14.0,37.9) 5.164 \u0026lt;0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eZ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-4.489\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-4.906\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section3\"\u003e \u003ch2\u003e2.3.3 Amenorrhea Rate and Adverse Reactions\u003c/h2\u003e \u003cp\u003eAmenorrhea Rate: After 3 months of treatment, the amenorrhea rate in the MIF group was 97.1% (34/35), significantly higher than the 58.3% (28/48) in the DNG group.\u003c/p\u003e \u003cp\u003eAdverse Reactions: The overall incidence of adverse reactions in the MIF group was 45.71% (16/35), significantly lower than the 75% (36/48) in the DNG group. (Table\u0026nbsp;\u003cspan refid=\"Tab6\" class=\"InternalRef\"\u003e6\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab6\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 6\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAdverse Reactions in Two Groups of Patients (%)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eAdverse Reaction\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eNumber of Patients (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMIF Group (n\u0026thinsp;=\u0026thinsp;35)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDNG Group (n\u0026thinsp;=\u0026thinsp;48)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHeadache\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2(5.71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4(8.33)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInsomnia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2(5.71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5(10.42)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHot Flashes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2(5.71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5(10.42)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWeight Gain\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4(11.42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8(16.67)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBreast Tenderness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2(5.71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6(12.50)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIrritability\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3(8.57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6(12.50)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIncreased Vaginal Discharge\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1(2.86)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2(4.17)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAdverse Reaction Rate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16(45.71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36(75.00)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study conducted a retrospective cohort analysis comparing the differences between mifepristone and dienogest in improving uterine volume reduction, amenorrhea rate, hemoglobin, and CA125 levels in patients with adenomyosis, as well as the adverse drug reactions. The results showed that the mifepristone group significantly outperformed the dienogest group in reducing uterine volume, had a higher amenorrhea rate, and a lower incidence of adverse reactions, providing a basis for clinical medication selection.\u003c/p\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003e3.1 Possible Mechanism Differences in Uterine Volume Reduction\u003c/h2\u003e \u003cp\u003eThe most striking result of this study is the huge difference in the effectiveness of the two drugs in reducing uterine volume. The MIF group achieved over a 20% reduction in uterine volume within just three months, while the DNG group's volume changes were not significant. This difference is deeply rooted in their distinctly different pharmacological mechanisms of action.\u003c/p\u003e \u003cp\u003eMifepristone, as a progesterone receptor antagonist, competitively binds to the progesterone receptor, not only inhibiting the proliferation of endometrial and ectopic endometrial cells and inducing their apoptosis but also possibly creating an unfavorable microenvironment for the survival of adenomyosis lesions by regulating local estrogen receptor expression, thus achieving significant uterine volume reduction[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. The results of this study showed that the median uterine volume in the mifepristone group decreased from 151.56 cm\u0026sup3; to 104.07 cm\u0026sup3;, with a significant difference within the group (P\u0026thinsp;\u0026lt;\u0026thinsp;0.01), which is consistent with a recent prospective study confirming that a low dose of mifepristone (10 mg/day) can effectively reduce uterine volume in patients with adenomyosis after three months of treatment[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. In contrast, dienogest, as a highly selective progestin, while capable of alleviating pain and reducing menstrual flow through ovulation suppression and direct anti-inflammatory effects, may have a weaker role in promoting the apoptosis of ectopic endometrial cells and reducing overall uterine volume[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. The slight change in uterine volume in the dienogest group in this study further supports the view that its effect on uterine reduction is limited, possibly related to its primary action on the endometrium rather than the myometrial lesions[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Therefore, dienogest may primarily relieve symptoms in the short term by suppressing inflammation and bleeding, while its effect on reducing uterine volume may require a longer treatment duration (e.g., six months or more) to manifest. The lack of significant change in uterine volume in the DNG group within three months aligns with this inference.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003e3.2 Differences in Amenorrhea Rate and Endometrial Response\u003c/h2\u003e \u003cp\u003eIn this study, the amenorrhea rate in the mifepristone group reached 97.1%, significantly higher than that in the dienogest group (58.3%). This high amenorrhea rate is closely related to mifepristone's potent antagonism of progesterone receptors and deep suppression of endometrial function. Conversely, although dienogest significantly caused endometrial atrophy (the study showed a reduction from 5.23 cm to 3.93 cm, P\u0026thinsp;\u0026lt;\u0026thinsp;0.01), its resulting amenorrhea rate was relatively low, possibly related to its higher incidence of breakthrough bleeding, which is consistent with reports of irregular bleeding during the early treatment phase of dienogest[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. However, despite the high amenorrhea rate in the mifepristone group, the endometrial thickness in the mifepristone group showed a slight increasing trend post-treatment (from 6.37\u0026thinsp;\u0026plusmn;\u0026thinsp;2.86mm to 6.78\u0026thinsp;\u0026plusmn;\u0026thinsp;3.30mm, P\u0026thinsp;\u0026gt;\u0026thinsp;0.05), while the dienogest group showed the expected significant thinning (from 5.23\u0026thinsp;\u0026plusmn;\u0026thinsp;2.32mm to 3.93\u0026thinsp;\u0026plusmn;\u0026thinsp;1.79mm, P\u0026thinsp;\u0026lt;\u0026thinsp;0.01). This may relate to the \u0026ldquo;non-antagonistic estrogen effect\u0026rdquo; caused by the progesterone receptor antagonism. By blocking the progesterone receptor, mifepristone relieves the normal antagonistic effect of progesterone on estrogen-induced endometrial proliferation. In the presence of ongoing estrogen secretion from the ovaries (albeit possibly at lower levels), the endometrium may exhibit a certain proliferative response or may be difficult to atrophy under continuous, non-antagonistic stimulation by estrogen[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec18\" class=\"Section2\"\u003e \u003ch2\u003e3.3 Improvement in Hemoglobin and CA125 Levels\u003c/h2\u003e \u003cp\u003eBoth groups of patients showed a significant increase in hemoglobin after treatment (P\u0026thinsp;\u0026lt;\u0026thinsp;0.01), and CA125 levels also significantly decreased (P\u0026thinsp;\u0026lt;\u0026thinsp;0.01), indicating that both drugs can effectively improve anemic conditions and suppress disease activity. CA125, a commonly used serum marker reflecting the severity of endometriotic disease, often shows a decline in levels associated with reduced lesion activity and symptom improvement[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Although the differences between groups were not significant, the baseline CA125 level in the mifepristone group was higher, and the post-treatment decrease was notable, suggesting its better inhibitory effect on more active or widespread lesions, which warrants further investigation in future larger sample studies.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec19\" class=\"Section2\"\u003e \u003ch2\u003e3.4 Comparison of Adverse Reactions\u003c/h2\u003e \u003cp\u003eIn this study, the overall incidence of adverse reactions in the mifepristone group (45.71%) was lower than that in the dienogest group (75%). The dienogest group reported higher rates of adverse reactions such as hot flashes, breast tenderness, irritability, and weight gain, which may be related to its feedback inhibition on the hypothalamic-pituitary axis and stronger progestogenic activity, consistent with literature reports[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. In contrast, the adverse reaction profile of mifepristone was relatively mild, and patient tolerance was good; a six-month safety study also reported no severe liver or kidney function abnormalities, supporting its safety for short-term use[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. This provides a reference for clinicians to personalize medication selection based on patients' sensitivity to side effects.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec20\" class=\"Section2\"\u003e \u003ch2\u003e3.5 Limitations of the Study\u003c/h2\u003e \u003cp\u003eThis study is a single-center retrospective design with a small sample size (n\u0026thinsp;=\u0026thinsp;84) and a short follow-up period (3 months), which may impact the generalizability of the results and the assessment of long-term efficacy (e.g., symptom recurrence, uterine volume rebound). Moreover, although the measurement of uterine volume used a standardized formula, it may still be subject to the subjectivity of the ultrasound operator. Future studies need to conduct multi-center, large-sample, long-term follow-up prospective randomized controlled trials and consider including quality of life scores and other patient-reported outcomes to provide higher levels of evidence.\u003c/p\u003e \u003c/div\u003e"},{"header":"Clinical Significance and Prospects","content":"\u003cp\u003eThis study suggests that for patients with adenomyosis who plan to place a Mirena IUD in a short time and require rapid pre-reduction of uterine volume to facilitate placement and enhance efficacy, mifepristone may be a superior pre-treatment medication choice compared to dienogest. Its rapid uterine reduction, high amenorrhea rate, and good tolerance make it of significant value in clinical practice. However, for patients needing long-term medication management for adenomyosis, long-term control of pain and reduction of menstrual flow symptoms are better suited for dienogest, as confirmed by many studies. Future research could further explore the long-term effects of the two drugs on ovarian function and fertility preservation, as well as optimize strategies for combination therapy (e.g., sequential therapy) to establish a more refined medication management pathway for adenomyosis.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn summary, the results of this retrospective cohort study indicate that in a short-term treatment period of three months, oral administration of 10 mg mifepristone daily shows significant superiority over daily administration of 2 mg dienogest in effectively reducing uterine volume in patients with adenomyosis, with a lower overall incidence of adverse reactions and better patient tolerance. Although both drugs are comparable in alleviating core symptoms such as dysmenorrhea and reducing menstrual flow, the dual advantage of mifepristone in improving uterine structure and enhancing safety makes it a highly potential new individualized treatment option particularly suited for patients with adenomyosis whose primary treatment goal is to reduce an enlarged uterus. Future large-scale prospective randomized controlled studies will further confirm these findings and provide more solid evidence for the application of mifepristone in the long-term management of adenomyosis.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eDNG\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eDienogest\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eMIF\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eMifepristone\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eGnRH-a\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eGonadotropin-releasing hormone agonist\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eLNG-IUS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eLevonorgestrel-releasing intrauterine system\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eUV\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eUterine volume\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eHb\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eHemoglobin\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCA125\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eCancer antigen 125\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eAE\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAdverse event\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eMRI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eMagnetic resonance imaging\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIUD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eIntrauterine device.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eEthics approval and consent to participate\u003c/h2\u003e \u003cp\u003e This study was approved by the Medical Ethics Committee of Peking University Shenzhen Hospital (Approval No: Peking University Shenzhen Hospital Institutional Review Board (Research) 2025 No. (323)). All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Written informed consent was obtained from all individual participants included in the study.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eConsent for publication\u003c/strong\u003e \u003cp\u003eNot applicable.\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eCompeting Interests\u003c/h2\u003e \u003cp\u003eThe authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eThe author(s) declare that no financial support was received for the research, authorship, and/or publication of this article.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eYZ and QH contributed to conception and design of the study. YZ wrote the draft of the manuscript. ML, YY, and YL organized the database and performed data collection. WW supervised the project. All authors contributed to manuscript revision, read, and approved the submitted version.\u003c/p\u003e\u003ch2\u003eAcknowledgements\u003c/h2\u003e \u003cp\u003eNot applicable.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe datasets generated and analyzed during the current study are not publicly available due to privacy and ethical restrictions but are available from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eBird CC, McElin TW, Manalo-Estrella P. The elusive adenomyosis of the uterus\u0026ndash;revisited. Am J Obstet Gynecol. 1972;112(5):583\u0026ndash;93.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eStruble J, Reid S, Bedaiwy MA. Adenomyosis: A Clinical Review of a Challenging Gynecologic Condition. J Minim Invasive Gynecol. 2016;23(2):164\u0026ndash;85.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChoi EJ, Cho SB, Lee SR, Lim YM, Jeong K, Moon HS, Chung H. Comorbidity of gynecological and non-gynecological diseases with adenomyosis and endometriosis. Obstet Gynecol Sci. 2017;60(6):579\u0026ndash;86.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAbbott JA. Adenomyosis and Abnormal Uterine Bleeding (AUB-A)-Pathogenesis, diagnosis, and management. Best Pract Res Clin Obstet Gynaecol. 2017;40:68\u0026ndash;81.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSchrager S, Yogendran L, Marquez CM, Sadowski EA. Adenomyosis: Diagnosis and Management. Am Fam Physician. 2022;105(1):33\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhou Xialing XJ, Qiao Lin M, Fang X. Observation on the clinical efficacy of mifepristone in the treatment of endometriosis. Chin J Family Plann. 2009;17(01):36\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCheng Jinhua ZW. Clinical observation on 52 cases of uterine fibroids treated with mifepristone. Chin J Practical Gynecol Obstet 2003(01):51\u0026ndash;2.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChe X, Wang J, Sun W, He J, Wang Q, Zhu D, Zhu W, Zhang J, Dong J, Xu J, et al. Effect of Mifepristone vs Placebo for Treatment of Adenomyosis With Pain Symptoms: A Randomized Clinical Trial. JAMA Netw Open. 2023;6(6):e2317860.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChe X, Wang J, He J, Yu Q, Sun W, Chen S, Zou G, Li T, Guo X, Zhang X. A new trick for an old dog: The application of mifepristone in the treatment of adenomyosis. J Cell Mol Med. 2020;24(2):1724\u0026ndash;37.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGalati G, Ruggiero G, Grobberio A, Capri O, Pietrangeli D, Recine N, Vignali M, Muzii L. The Role of Different Medical Therapies in the Management of Adenomyosis: A Systematic Review and Meta-Analysis. J Clin Med 2024, 13(11).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu Lu WJ, Gao Xinran W, Molin L, Meng S, Chunliang G, Hongyan. Comparative analysis of the efficacy of dienogest and LNG-IUS in the treatment of internal and external adenomyosis. Chin J Obstet Gynecol. 2025;60(04):281\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi RR, Xi Q, Tao L, Sheng W, Zhao CC, Wu YJ. A systematic review and Bayesian analysis of the adverse effects of dienogest. BMC Pharmacol Toxicol. 2024;25(1):43.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMurphy AA, Kettel LM, Morales AJ, Roberts V, Parmley T, Yen SS. Endometrial effects of long-term low-dose administration of RU486. Fertil Steril. 1995;63(4):761\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVannuccini S, Petraglia F. Recent advances in understanding and managing adenomyosis. \u003cem\u003eF1000Res\u003c/em\u003e 2019, 8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBenetti-Pinto CL, Mira TAA, Yela DA, Teatin-Juliato CR, Brito LGO. Pharmacological Treatment for Symptomatic Adenomyosis: A Systematic Review. Rev Bras Ginecol Obstet. 2019;41(9):564\u0026ndash;74.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFu J, Song H, Zhou M, Zhu H, Wang Y, Chen H, Huang W. Progesterone receptor modulators for endometriosis. Cochrane Database Syst Rev. 2017;7(7):Cd009881.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Adenomyosis, Mifepristone, Dienogest, Uterine volume, Efficacy, Safety","lastPublishedDoi":"10.21203/rs.3.rs-8968744/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8968744/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective\u003c/h2\u003e \u003cp\u003eThis study aims to systematically compare the short-term efficacy and safety differences between daily oral 2 mg Dienogest (DNG) and daily oral 10 mg Mifepristone (MIF) in the treatment of patients with symptomatic adenomyosis, focusing on the impact of both drugs on uterine volume, clinical symptoms (dysmenorrhea, menorrhagia), and adverse events, providing a basis for individualized medication treatment.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA single-center retrospective cohort study was conducted, including 83 patients diagnosed with adenomyosis who received drug treatment from May 1, 2023, to May 1, 2025. The patients were divided into the Mifepristone group (35 cases, 10 mg/day) and the Dienogest group (48 cases, 2 mg/day), with treatment lasting for 3 months. The uterine volume, endometrial thickness, amenorrhea rate, hemoglobin, CA125 levels, and adverse events were compared between the two groups before and after treatment. Statistical analysis was performed using SPSS 27.0, with P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 considered statistically significant.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eAfter 3 months of treatment, the median uterine volume in the MIF group significantly decreased from 151.56 cm\u0026sup3; to 104.07 cm\u0026sup3; (P\u0026thinsp;\u0026lt;\u0026thinsp;0.01), with a reduction value of 32.29 cm\u0026sup3;, significantly higher than the 8.103 cm\u0026sup3; in the DNG group (P\u0026thinsp;\u0026lt;\u0026thinsp;0.01). The amenorrhea rate in the MIF group (97.1%) was significantly higher than that in the DNG group (58.3%). Both groups showed a significant increase in hemoglobin and a significant decrease in CA125 (both P\u0026thinsp;\u0026lt;\u0026thinsp;0.01). The DNG group showed a significant thinning of endometrial thickness (P\u0026thinsp;\u0026lt;\u0026thinsp;0.01), while the MIF group did not show significant changes (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05). The overall adverse reaction rate in the MIF group (45.71%) was lower than that in the DNG group (75%).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eIn a 3-month pre-treatment period, Mifepristone significantly outperformed Dienogest in reducing uterine volume and improving the amenorrhea rate in patients with adenomyosis, while also exhibiting better tolerance.\u003c/p\u003e","manuscriptTitle":"Comparison of the Efficacy and Safety of Mifepristone and Dienogest in the Treatment of Symptomatic Adenomyosis: A Retrospective Cohort Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-11 11:04:51","doi":"10.21203/rs.3.rs-8968744/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"e312e7bd-248f-4ccd-84e5-7718fb80ad24","owner":[],"postedDate":"March 11th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-04-06T06:25:40+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-11 11:04:51","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8968744","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8968744","identity":"rs-8968744","version":["v1"]},"buildId":"B-jG_2CBjPDmsCi4Wdhf-","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}