{"paper_id":"49c797c6-8da5-4ac1-9c17-d38bc2d5e50f","body_text":"Orginal Article  | JOGCR. 2026; 11(9): 830-836 \n     Volume 11, September 2026       Journal of Obstetrics, Gynecology and Cancer Research \n Journal of Obstetrics, Gynecology and Cancer Research | ISSN: 2476-5848 \n \n \nChanges in CA125 and CA19-9 Biomarkers and Lesion Size in Deep \nInfiltrating Endometriosis Patients Treated with Dienogest \n \nShima Mohammadian1 , Mahin Seifi Alan2,3* , Zahra Sadat Khonsarian4 , Kobra Hosseini2,3 , \nHaniyeh Rashidi3  \n \n1. Department of Gynecology Oncology, Kamali Teaching Hospital, Alborz University of Medical Sciences, Karaj, Iran \n2. Cardiovascular Research Center, Alborz University of Medical Sciences, Karaj, Iran \n3. Clinical Research and Development Center of the Kamali Hospital, Alborz University of Medical Sciences, Karaj, Iran \n4. Department of Obstetrics and Gynecology, School of Medicine, Kamali Hospital, Alborz University of Medical \nSciences, Karaj, Iran \nArticle Info  ABSTRACT \n  \n 10.24200/jogcr.11.9.830 \n \n \n \nBackground & Objective: Deep Infiltrating Endometriosis (DIE) is a severe form of \nendometriosis with limited tools for objective assessment of therapeutic efficacy. \nAlthough CA125 and CA19‑9 are elevated in many patients, their utility in monitoring \nresponse to hormonal therapyethi remains unclear. This study was conducted with aim \nto evaluate the changes in imaging findings and the biomarkers CA125 and CA19-9 in \nDeep Infiltrating Endometriosis (DIE) patients who underwent Dienogest (DNG) \ntreatment. \nMaterials & Methods: This prospective cohort study was conducted on women \ndiagnosed with DIE over a 6 -month period at Kamali Hospital in Alborz, Iran. All \nparticipants received consistent oral Verogest 2 mg daily for six months. Endometriosis \ninfiltration depth as well as CA12 5 and CA19 -9 serum levels were assessed at the \nbaseline and six months after DNG treatment. Data were analyzed using SPSS software \n(version 22.0). P<0.05 was considered as statistically significant. \nResults: The study included 87 DIE patients, with a mean age 37.6±6.4 years and a \nmedian duration of endometriosis of 4.0 years (Interquartile Range (IQR): 2.0-8.0). The \nmedian size of endometriosis lesions significantly decreased from 7.0 cm (IQR: 4.0-\n14.0 cm) at baseline to 4.0 cm (IQR: 2.0-9.5 cm) after six months of DNG treatment \n(P<0.001); the median decrease in lesion size was -34.6% (-55.8%, -16.7%). CA125 \nlevels significantly decreased from a median of 80.0 (IQR: 46.3-101.0) to 40.0 (30.0-\n73.0), and CA19-9 levels decreased from 68.0 (45.0-96.2) to 34.0 (28.0-56.0) (P<0.001 \nfor both). The treatment was well tolerated, with no clinically significant adverse effects \nreported among the patients. \nConclusion: These findings suggest that DNG may be an effective therapeutic option \nfor the management of DIE, leading to improvements in both imaging characteristics \nand relevant biomarkers. \nKeywords: Deep infiltrating endometriosis, Dienogest, CA125, CA19 -9, \nEndometriosis lesion size \n \nReceived: 2025/02/12 \nAccepted: 2025/04/26 \nPublished Online: 18 Jul. 2026 \n \n \n \n \n \nCorresponding Information:  \nMahin Seifi Alan, \nCardiovascular Research Center, Alborz \nUniversity of Medical Sciences, Karaj, Iran \n \nEmail: mah.seifi97@gmail.com \n \n \nCopyright © 2026, This is an original open-access article distributed under the terms of the Creative Commons Attribution-noncommercial \n4.0 International License which permits copy and redistribution of the material just in noncommercial usages with proper citation . \n \n \n1. Introduction\nDeep Infiltrating Endometriosis (DIE) is a severe \nform of endometriosis marked by the invasion of \nendometrial-like tissue into adjacent structures outside \nthe uterus, such as the uterosacral ligaments, bladder, \nand rectum (1). The persistent challenges in managing \nof DIE have prompted a growing interest in exploring \nnew therapeutic options to enhance its clinical \noutcomes in recent years (2). \nGiven the pivotal role of estrogen in the development \nand progression of endometriosis, hormonal treatments \nsuch as Combined Hormonal Contraceptives (CHC) \nand progestin are currently utilized as first -line \ntherapeutic options in affected individuals (3-5). \nDienogest (DNG), a unique fourth -generation \nprogestin, which selectively binds to progesterone \nreceptors, has emerged as a promising pharmacological \nagent in managing this condition. In vivo and vitro \nstudies, DNG shows strong progestogenic \neffectiveness alongside moderate estrogen-suppressing \neffects. Additionally, it exhibits anti -inflammatory, \n\n\n831 CA125, CA19-9, and Lesion Size in Endometriosis \n      Volume 11, September 2026       Journal of Obstetrics, Gynecology and Cancer Research \nanti-proliferative, and antiangiogenic properties that \neffectively decrease the growth of endometrial -like \ntissue (6,7).  \nCA125 and CA19 -9 biomarkers, produced by cells \nin the ovaries, fallopian tubes, and gastrointestinal \ntract, exhibit elevated levels in women with \nendometriosis attributed to the inflammation and \nirritation in these regions. Given their association with \nthe severity of endometriosis, a decrease in their levels \ncould potentially indicate treatment success (8-11). \nAvailable evidence on the value of DNG in treating \nDIE is still limited and mainly focused on subjective \nparameters such as pain relief and quality of life to \nassess the effectiveness of endometriosis treatments \n(12-15). Therefore, the present study was conducted \nwith aim to monitor changes in biomarkers CA125 and \nCA19-9, as well as changes in imaging findings to \ntrack disease activity and response to treatment. \n \n2. Materials and Methods \nThis prospective observational cohort study was \nconducted on women diagnosed with DIE over a 6 -\nmonth period at Kamali Hospital in Alborz, Iran. The \nstudy included women with confirmed DIE in the \nuterosacral ligaments through imaging or surgical \nfindings. T he pregnant women, and individual with \npelvic infections, abscesses, or cancer were not \nincluded. None of the women in this study had \nundergone prior surgical treatment for endometriosis. \nParticipants received DNG treatment in the form of \noral Verogest 2 mg tablets, taken once daily throughout \nthe study duration. Serum levels of the biomarkers \nCA125 and CA19 -9 were evaluated using ELISA at \nbaseline and 6-month follow-up. Endometriosis lesion \nsize was assessed by specialized sonographers using a \ncomprehensive approach involving three -dimensional \ntransvaginal/transrectal and abdominal ultrasound at \nbaseline and 6 months after treatment. \nDemographic and clinical characteristics, including \nage, Body Mass Index (BMI), endometriosis grade, \nand, marital status, employment status, education, \nSexual Transmitted Disease (STD), smoking, \nhormonal contraceptive, previous Cesarean section, \nage at first delivery, number of delivery, endometriosis \nduration were collected using a checklist at study visits.  \nThe data were summarized using appropriate \ndescriptive statistics, mean ( Standard Deviation [SD]) \nor median (Interquartile Range [IQR]), for continuous \nvariables and frequency (%) for categorical variables. \nPaired data on biomarkers levels and lesion size was \nanalyzed using Wilcoxon signed -rank test. All \nstatistical analyses were performed using SPSS version \n22.0. P<0.05 was considered as statistically significant. \n \n3. Results \nThe study included 87 patients diagnosed with DIE \nin the uterosacral ligaments, with an average age of \n37.6±6.4 years. All participants completed the study. \nAmong the participants, 74.7% (n=65) were married, \n41.9% (n=36) had an Academic education, and 54% \n(n=47) were employed. Additionally, 20% had a \nhistory of STDs, 8% were current smokers, and 6% \nwere using hormonal contraceptives. A total of 39.5% \nhad a history of cesarean section. Furthermore, 7.1% \nwere classified as overweight or obese (BMI>25.0 \nkg/m2). Regarding endometriosis grading, the majority \n(69%) were classified as grade IV and none of the \nparticipants had grade I. The median duration of \nendometriosis was 4.0 years (IQR: 2.0 -8.0) (Table 1). \nOverall, a reduction in the DIE Size was observed in \n80.0% (64/80) of participants, but increased 6% (5/80) \nor remained unchanged 14% (11/80) in others.  \nThe median endometriosis lesion size significantly \ndecreased from 7.0 cm (interquartile range: 4.0 -14.0 \ncm) at baseline to 4.0 cm (interquartile range: 2.0 -9.5 \ncm) after six months of DNG treatment, representing a \nmedian reduction of 34.6% (interquartile r ange: -\n55.8% to -16.7%) (P<0.001) (Table 2). \nTo assess the impact of DNG on CA125 and CA19 -\n9 biomarker levels, the analysis focused on participants \nwith abnormal levels of these markers. Initially, 61.2% \n(52/85) of participants exhibited elevated CA125 \nlevels, which decreased to 38.5% (32/83) after s ix \nmonths of treatment. The median CA125 level in these \nindividuals significantly decreased from 80.0 (46.3, \n101.0) to 40.0 (30.0, 73.0). Similarly, 57.0% (49/86) of \nparticipants had abnormal CA19 -9 levels at baseline, \nwhich decreased to 26.2% (22/84) post -treatment. The \nmedian CA19 -9 level in these participants also \nsignificantly decreased from 68.0 (45.0, 96.2) to 34.0 \n(28.0, 56.0) (P<0.001) (Table 2). \nNone of the participants reported experiencing any \nsevere adverse events associated with DNG treatment, \nsuch as persistent nausea and vomiting, jaundice, dark \nurine, or severe abdominal pain. \n \n \n \n \n \n \n\nShima Mohammadian, et al. 832 \n      Volume 11, September 2026       Journal of Obstetrics, Gynecology and Cancer Research \nTable 1. Baseline characteristics of participants \nBaseline Characteristics  Percent%(Frequency)/ Mean (SD)/ Median (IQR) \nAge (year), Mean (SD) 37.6(6.4) \nMarital status, % (N) \n \nMarried 74.7%(65) \nDivorced 11.5%(10) \nNon married 13.8%(12) \nEmployment status, % (N) \nEmployed 54.0%(47) \nNon employed 46.0%(40) \neducation, % (N) \nElementary School 12.8%(11) \nHigh school 45.3%(39) \nAcademic education 41.9%(36) \nSTD (Yes), % (N) 20.0%(17) \nSmoking (Yes), % (N) 8.0%(7) \nHormonal contraceptive (Yes), % (N) 6.0%(5) \nPrevious Cesarean Section (yes), % (N) 39.5%(34) \nAge at first delivery, Mean (SD) 23.2(4.6) \nNumber of delivery, Median (IQR) 1.0(0.0, 2.0) \nBMI % (N) \nUnder weight 15.5%(13) \nNormal 77.4%(65) \nOver weight/obese 7.1%(6) \nEndometriosis grade, % \n(N) \nI 0.0%(0) \nII 15.5%(13) \nIII 15.5%(13) \nIV 69%(58) \nEndometriosis duration, Median (IQR) 4.0(2.0-8.0) \nSD: Standard Deviation, BMI: Body Mass Index, IQR: Interquartile Range, N: Number \n \nTable 2. Changes in CA125 and CA19-9 Biomarkers and Lesion Size in participants \n CA125 biomarker CA19-9 biomarker DIE Size in Sonography \nMedian scores (IQR) \nBaselinea 80.0(46.3, 101.0) 68.0(45.0, 96.2) 7.0(4.0, 14.0) \n6 month after treatment 40.0(30.0, 73.0) 34.0(28.0, 56.0) 4.0(2.0, 9.5) \n% Difference -26.9(-51.1, -4.0) -25.8(-48.3, -7.7) -34.6%(-55.8, -16.7) \nP-value <0.001 <0.001 <0.001 \n% abnormalb \nBaseline 61.2%(52/85) 57.0%(49/86) NA \n6 month after treatment 38.5%(32/83) 26.2%(22/84) NA \nP-value <0.001 <0.001 NA \nReduction in the \nparameter  90.0%(45/50) 97.9%(46/47) 80.0%(64/80) \na Calculated in individuals with abnormal level of biomarkers \nb CA125>35 U/mL and CA19-9>37 U/mL \n\n833 CA125, CA19-9, and Lesion Size in Endometriosis \n      Volume 11, September 2026       Journal of Obstetrics, Gynecology and Cancer Research \n4. Discussion \nThe purpose of this study was to assess the impact of \nDNG treatment on imaging findings and the levels of \nthe biomarkers CA125 and CA19 -9 in patients with \nDIE. The results showed that after six months of DNG \ntreatment, the majority of  patients demonstrated \nreductions in the levels of CA125 and CA19 -9, with \napproximately half of the participants having these \nbiomarkers fall within the normal range. Furthermore, \nthe study found a significant decrease of around 40% \nin the median size of DIE lesions. Regarding safety, in \nour study, none of the patients experienced severe side \neffects during the study. \nIn line with our research, Piacenti et al. reported that \nthe mean size of DIE lesions decreased from 16±5.2 \nmm at baseline to 8.7±2.8 mm at 6 months after \ntreatment with DNG, representing an approximately \n45% reduction (16). Other previous studies \ninvestigating the use of DNG in treating endometriosis, \nhave also reported that DNG efficiently reduced the \nsize of endometriotic lesions (16-19); overall, they \nfound a reduction in the mean lesion volume ranging \nfrom 41% to 75% after 6 months (17-19), and up to \n76% after 12 months of DNG treatment (19).  \nIn our study, approximately 60% of patients with \nDIE had elevated levels of CA125 and/or CA19 -9. \nFindings from a meta -analysis have indicated that \nserum levels of CA125 and CA19 -9 may serve as \nuseful biomarkers for the noninvasive diagnosis of \nendometriosis (20). Furthermore, a recent study found \nthat women with DIE had higher serum levels of \nCA125 compared to those with ovarian endometrioma \nbut without DIE (21).  \nAdditionally, some researchers have argued that the \nserum levels of CA125 and CA19 -9 could act as \nindicators for assessing the therapeutic response in \npatients with DIE. Consistent with our findings, a study \nconducted on 121 women diagnosed with recurrent \nendometriosis revealed a significant decrease in mean \nCA125 levels from 80.04 U/mL at baseline to 33.11 \nU/mL after 6 months of treatment with DNG (22). \nIn the present study, a small proportion of \nparticipants did not experience a reduction in DIE \nlesion size (20%) or serum levels of CA125 (10%) and \nCA19-9 (2%) in response to DNG treatment. Direct \ncomparisons with previous studies are challenging due \nto di fferences in patient populations, definitions of \nefficacy, and primary outcome measures, which have \nled to a wide range of reported non -response rates, \nranging from 0.3% to 13.22% in different studies (22-\n27). There could be several reasons why some patients \nmay not respond well to DNG treatment; these reasons \ninclude the advanced severity of their endometriosis, \nindividual variations in medication response, the \ndevelopment of drug resistance over time, underl ying \nhealth factors or genetic predispositions affecting \ntreatment effectiveness, potential misdiagnosis leading \nto ineffective therapy, or patient non -compliance with \nthe prescribed treatment plan. \nRegarding the mechanism of action, DNG is a hybrid \nprogestin with excellent oral bioavailability and a \npotent progestational impact. It inhibits gonadotropin \nsecretion, exhibits localized antiproliferative and anti -\ninflammatory effects on endometriotic les ions, and \ncreates a predominantly gestagenic endocrine \nenvironment, ultimately resulting in the reduction of \nendometriotic lesions (28-30). Additionally, DNG has \nbeen shown to suppress ovulation and enhance the \nresponsiveness to progestin treatment in endometriotic \ntissue (29,31,32). \nIn our study, none of the patients experienced any \nsevere side effects during the treatment period. The \nsafety profile of DNG appears generally satisfactory \nfor individuals with endometriosis, as demonstrated in \nclinical trials where DNG 2 mg exhibited goo d \ntolerability for up to 65 weeks. In a study on the safety \nand tolerability of dienogest in endometriosis, common \nadverse events occurred in less than 10% of patients \nand were generally mild to moderate in severity (23). \nLong-term use of DNG for up to 5 years has also shown \na favorable safety profile (33,34). Treatment with DNG \n2 mg can lead to endometrial regression and irregular \nbleeding, which may decrease over time. The \noccurrence of amenorrhea varied during treatment, and \nalthough spotting may occur with long-term DNG use, \nit resulted in very few discontinuations in clinical trials \n(23,35). Initiating DNG 2 mg at the beginning of \nmenses or using a GnRH agonist before starting long -\nterm DNG therapy may help reduce the initial irregular \nbleeding. Consistent and regular intake of DNG is \nessential to maintain the ovulation blockade due to its \nshort half-life (36,37). \n \n5. Conclusion \nThe results of this study indicated that DNG could be \na promising therapeutic option for patients with DIE. \nThe reductions in endometriosis lesion size, as well as \nthe significant decreases in the biomarkers CA125 and \nCA19-9, suggest that DNG treatment may  lead to \nmeaningful improvements in both radiographic and \nbiochemical markers of disease. \n \n6. Declarations \nAcknowledgments \nThe researchers appreciated the Clinical Research \nDevelopment Units of Kamali Hospital in Alborz \nUniversity of Medical Sciences. \n \nEthical Considerations \nThe study was approved by ethics committee of \nAlborz University of Medical Sciences, Alborz, Iran, \nand all participants provided written informed consent  \n(IR.ABZUMS.REC.1401.317). \n\nShima Mohammadian, et al. 834 \n      Volume 11, September 2026       Journal of Obstetrics, Gynecology and Cancer Research \nAuthors' Contributions \nShima Mohammadian: Conceptualization, Data \ncuration, Investigation, Writing - original draft, \nVisualization. Mahin Seifi Alan: Methodology, Formal \nanalysis, Validation, Writing - original draft, Writing - \nreview and editing, Supervision, Project \nadministration. Zahra Sadat Khonsarian: Investigation, \nResources, Data collection, Validation. Kobra \nHosseini: Software, Formal analysis, Writing - review \nand editing. Haniyeh Rashidi: Data collection, Formal \nanalysis, Writing- review and editing. All authors have \nread and approved the final version of the manuscript \nand agree to be accountable for all aspects of the work. \n \nConflict of Interest \nThe authors declare that they have no conflict of \ninterest. \n \nFund or Financial Support \nNot applicable. \n \n \n \n \n \n1. Tosti C, Pinzauti  S, Santulli P, Chapron C, \nPetraglia F. Pathogenetic mechanisms of deep \ninfiltrating endometriosis. Reprod Sci. \n2015;22(9):1053-9. \n[doi:10.1177/1933719115592713] \n2. D’Alterio MN, D’Ancona G, Raslan M, Tinelli \nR, Daniilidis A, Angioni S. Management \nChallenges of Deep Infiltrating Endometriosis. \nInt J Fertil Steril. 2021;15(2):88 -94. \n[doi:10.22074/ijfs.2020.134689] \n3. Kalaitzopoulos DR, Samartzis  N, Kolovos GN, \nMareti E, Samartzis EP, Eberhard M, et al. \nTreatment of endometriosis: a review with \ncomparison of 8 guidelines. BMC Womens \nHealth. 2021;21(1):397. 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Maintenance therapy with dienogest following \ngonadotropin-releasing hormone agonist \ntreatment for endometriosis -associated pelvic \npain. Eur J Obstet Gynecol Reprod Biol. \n2011;157(2):212-6. \n[doi:10.1016/j.ejogrb.2011.03.012] \n37. Murji A, Biberoğlu  K, Leng J, Mueller MD, \nRömer T, Vignali M, et al. Use of dienogest in \nendometriosis: a narrative literature review and \nexpert commentary. Curr Med Res Opin. \n2020;36(5):895-907. \n[doi:10.1080/03007995.2020.1744120] \n \n \n \n \n \n \n \n  \nHow to Cite This Article:  \nMohammadian Sh, Seifi Alan M, Sadat Khonsarian  Z, Hosseini K, Rashidi H. Changes in CA125 and CA19 -9 \nBiomarkers and Lesion Size in Deep Infiltrating Endometriosis Patients Treated with Dienogest . J Obstet Gynecol \nCancer Res. 2026;11(9):830-836. \nDownload citation:                             RIS | EndNote | Mendeley |BibTeX |","source_license":"CC0","license_restricted":false}