{"paper_id":"5a4be28f-c473-4e95-bdc4-b7acedb1277a","body_text":"RESEARCH Open Access\nMiddle East Fertility\nSociety Journal\n© The Author(s) 2025. Open Access  This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, \nsharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and \nthe source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this \narticle are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included \nin the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will \nneed to obtain permission directly from the copyright holder. To view a copy of this licence, visit  h t t p  : / /  c r e a  t i  v e c  o m m  o n s .  o r  g / l i c e n s e s / b y / 4 . 0 /.\nAbdallah et al. Middle East Fertility Society Journal           (2025) 30:68 \nhttps://doi.org/10.1186/s43043-025-00287-w\n*Correspondence:\nAhmed Soliman\nahmedsolimann9090@gmail.com\n1Obstetrics and Gynecology Department, Faculty of Medicine, Benha \nUniversity, Benha, Egypt\n2Obstetrics and Gynecology Department, Aswan Specialized Hospital, \nAswan, Egypt\n3Faculty of Medicine, Mansoura University, 6 Al-ashqar St., of Al-Gomhoria \nSt., Mansoura, Egypt\nAbstract\nBackground Endometriosis is a chronic gynecological condition associated with pelvic pain, dysmenorrhea, \ndyspareunia, and impaired quality of life. Medical management aims to reduce symptoms and prevent recurrence. \nThe primary objective of this study was to compare the efficacy of Dienogest versus Oral Contraceptive Pills (OCPs) \nin controlling endometriosis-associated pelvic pain. The secondary objective was to compare the improvement in \nhealth-related quality of life (QoL) between the two groups.\nMethods This prospective cohort study included 80 women with histologically confirmed endometriosis, divided in \ntwo groups. Group I (n = 40) received Dienogest 2 mg daily, and Group II (n = 40) received an OCP containing ethinyl \nestradiol 0.03 mg and drospirenone 3 mg daily for 24 weeks. The primary outcome was the change in endometriosis-\nassociated pelvic pain from baseline to the end of treatment assessed using the total symptoms and sign severity \nscore (Biberoglu and Behrman score).\nResults Baseline demographic and clinical characteristics were similar between groups (p > 0.05). Both treatments \nsignificantly improved pelvic pain, dysmenorrhea, and dyspareunia (p < 0.001). However, Dienogest demonstrated \ngreater reduction in total symptoms and sign severity scores (mean difference 5.3 vs. 3.82, p < 0.001) and higher \npercentage improvement (64.2% vs. 48.1%, p = 0.002). More patients in the Dienogest group shifted to mild/moderate \nseverity (p = 0.04). EHP-30 scores showed significantly better post-treatment improvement with Dienogest (mean \nreduction 19.4 vs. 12.3, p < 0.001).\nConclusion Both Dienogest and OCPs effectively reduce endometriosis-associated pain, but Dienogest provides \nsuperior improvement in symptom severity and quality of life, supporting its use as a more effective long-term \ntherapeutic option.\nKeywords Endometriosis, Dienogest, Oral contraceptive pills, Pelvic pain\nEfficacy of oral contraceptive pills versus \ndienogest on endometriosis pain scores: \na prospective cohort study\nMahmoud Abdallah1, Asmaa S. Mohamed2, Ahmed Soliman3* and Walid M. Tawfik1\n\nPage 2 of 8\nAbdallah et al. Middle East Fertility Society Journal            (2025) 30:68 \nIntroduction\nEndometriosis is a chronic disease that affects approxi -\nmately 10% of women of reproductive age [ 1]. Although \nendometriosis can be completely asymptomatic, acute \nand chronic pelvic pain, dysmenorrhea, dyspareunia, \ndyschezia, chronic fatigue, and infertility are the most \ncommon symptoms that have a significant effect on the \nquality of life (QOL) of patients. According to various \nstudies, 60%–70% of women with endometriosis suffer \nfrom disorders such as poor QOL, depression, and anxi -\nety [2].\nAlthough the pathogenesis is enigmatic, endometriosis \nis characterized by lesions dependent on estrogen pro -\nduction, which promotes the proliferation and survival of \nendometrial tissue outside the uterus. The severity of the \ndisease and associated pain is closely linked to the cyclic \nfluctuations of ovarian hormones, driving inflammation \nand lesion growth [3]. As a chronic and recurrent disease \nwith an adverse effect on patients’ physical and psycho -\nlogical well-being, it requires constant symptom control \n[4].\nMedical management for endometriosis primarily uti -\nlizes hormonal therapies to create a hypoestrogenic envi -\nronment and suppress the growth of ectopic endometrial \nlesions. These treatments include gonadotropin-releasing \nhormone (GnRH) agonists/antagonists, progestins, and \ncombined oral contraceptive pills (OCPs) [ 5]. OCPs have \nlong been a cornerstone of treatment, primarily working \nthrough pituitary suppression to inhibit ovulation and \nreduce endogenous estrogen levels, thereby causing atro -\nphy of the endometrial implants [6].\nIn addition to OCPs, another treatment that has \nbeen widely studied for the management of endome -\ntriosis is Dienogest. Dienogest is a synthetic progestin, \na 19-nortestosterone derivative, with good oral bioavail -\nability and high selectivity for progesterone receptors. \nIt has anti-ovulatory, antiproliferative, and inhibitory \neffects [ 7]. Dienogest has been shown to inhibit nerve \ngrowth factor expression induced by tumor necrosis fac -\ntor alpha or interleukin beta, a key mediator in generat -\ning pain associated with endometriosis. Its inhibitory \naction exhibits a progestogenic response on endometrial \nstromal cells in vitro, such as decidualization, increased \nprolactin production, and growth retardation [ 7]. Unlike \nother progestins, Dienogest does not have androgenic \nproperties, glucocorticoid activity, or mineralocorticoid \nactivity. Several studies have shown a significant improve-\nment in pain symptoms and quality of life following treat-\nment with Dienogest [ 8, 9]. The primary objective of this \nstudy was to compare the efficacy of Dienogest with a \ncommonly used oral contraceptive pill containing ethinyl \nestradiol and drospirenone for the control of endometri -\nosis-associated pelvic pain. The secondary objective was \nto compare the improvement in health-related quality of \nlife, as assessed by the EHP-30, between the two treat -\nment groups.\nMethods\nStudy design and approval\nWe conducted a prospective cohort study on patients \nwith a histologically confirmed diagnosis of endome -\ntriosis in the department of obstetrics and gynecology \nof Benha University Hospital from June 2024 to 2025. \nThe study was conducted in accordance with the Hel -\nsinki Principles, and the study protocol was revised and \napproved by the ethical committee and the institutional \nresearch board under reference no. (MS-1–9−2025).  \nAll patients provided informed written consent before \nenrollment.\nEligibility criteria\nWomen aged between 18 and 50 years with a normal \nbody mass index (BMI) of less than 25  kg/m 2, regular \nmenstrual cycles, and symptomatic endometriosis with \nmenstrual pain for more than 6 months. Exclusion cri -\nteria included pelvic pain originating from other organs \n(such as the gastrointestinal or genitourinary systems), \na plan for pregnancy in the near future, use of gonado -\ntropin-releasing hormone (GnRH) analog treatment or \nother hormonal drugs within the last 3 months, the pres -\nence of other gynecological diseases or malignancy, and \nany contraindications to OCPs or Dienogest use.\nPatients’ evaluation and grouping\nAll eligible patients underwent a comprehensive evalu -\nation at baseline, which included complete history tak -\ning, physical examinations, and a series of investigational \nstudies. A thorough physical examination was conducted \nto exclude systemic diseases and other sources of pain. \nRoutine laboratory investigations were performed. A \ntransvaginal ultrasound (TVS) using a 7.5  MHz vagi -\nnal probe was performed to specifically look for ovarian \nendometriomas. A systematic evaluation of the uterus \nand ovaries was carried out, including measurement of \novarian size in three orthogonal planes and assessment of \novarian mobility using gentle pressure.\nPatients were divided into two equal groups based \non physician choice: Group A received Dienogest 2  mg \ntablet once daily for 24 weeks while Group B received \n0.03 mg ethinyl estradiol combined with 3 mg drospire -\nnone once daily for 24 weeks. Prior to the initiation of \nmedical therapy, all patients underwent a standardized \ntherapeutic laparoscopic procedure for definitive histo -\nlogical diagnosis and surgical management. The medi -\ncal regimen was initiated in the first week following the \nprocedure.\nLaparoscopy was performed under general anesthesia \nto allow for full visualization, definitive diagnosis, and \n\nPage 3 of 8\nAbdallah et al. Middle East Fertility Society Journal            (2025) 30:68 \ntherapeutic management. Lesions suspicious for endo -\nmetriosis were identified and biopsied using punch for -\nceps. Biopsies were taken from all suspicious lesions, \nwith histological confirmation being mandatory for study \ninclusion. The presence of lesions was mapped; however, \nanatomical severity was not formally categorized using \nthe r-ASRM classification. The biopsy sites were coagu -\nlated by endocoagulation or bipolar coagulation. Patients \nwith ovarian endometriomas were managed by cyst enu -\ncleation, followed by endocoagulation of the wound base \n(80 − 100 ∘C) and, when required, closure with endosu -\ntures using an extracorporeal knotting technique [ 10]. \nAll biopsies were sent for histological confirmation of \nendometriosis.\nStudy outcomes\nThe primary outcome was the change in endometriosis-\nassociated pelvic pain from baseline to the end of treat -\nment assessed using the total symptoms and sign severity \nscore (Biberoglu and Behrman score) (B&B) scale (a com-\nposite score derived from a 0–3 scale for dysmenorrhea, \npelvic pain, dyspareunia, and palpation findings of ten -\nderness and induration). The pelvic pain score, ranging \nfrom 0 to 9, was based on the severity of pelvic discom -\nfort, dysmenorrhea, and dyspareunia.\nPelvic pain was categorized as none (0), mild (1), mod -\nerate (2), or severe (3). Dysmenorrhea was rated from \nnone (0) to severe (3, indicating incapacitation). Dyspa -\nreunia was similarly scored from none (0) to severe (3, \nindicating avoidance of intercourse). The physical sign \nscore, ranging from 0 to 6, was based on assessments of \npelvic tenderness and induration. The final total symp -\ntom and sign severity score, ranging from 0 to 15, was the \nsum of the pelvic pain score and the physical sign score, \nwith categories ranging from none to very severe.\nSecondary outcomes include health-related quality of \nlife evaluated at baseline and post-treatment using the \nvalidated EHP-30 which has scores ranging from 0 (best \nhealth status) to 100 (worst health status).\nStatistical analysis\nData analysis was performed using SPSS version 26 (IBM \nCorp., Chicago, IL, USA). Parametric quantitative vari -\nables were expressed as mean ± standard deviation (SD) \nand compared between groups using the unpaired Stu -\ndent’s t-test. Non-parametric quantitative variables were \nexpressed as median and interquartile range (IQR) and \nanalyzed using the Mann–Whitney U test. Categorical \nvariables were expressed as frequency and percentage \nand analyzed using the Chi-square test or Fisher’s exact \ntest as appropriate. A two-tailed p-value < 0.05 was con -\nsidered statistically significant.\nSample size estimation\nGPower® version 3.1 was used for calculations of sample \nsize, statistical calculator based on 95% confidence inter -\nval and power of the study 95% with α error 5%, and \neffect size of 0.56. According to a similar previous study \n[11], the mean pain score at the initial assessment was \ncalculated as 8.40 ± 1.3 and decreased to 2.44 ± 2.1 at the \nthree-month follow-up with using Dienogest therapy (p < \n0.001). Based on this assumption and with dropout 10%, \nsample size was calculated according to these values pro -\nduced a samples size of 80 cases (40 cases for each group) \nto find such a difference.\nResults\nBaseline demographic and clinical characteristics\nThe study included 80 women with histologically con -\nfirmed endometriosis, equally divided into the Dienogest \nGroup ( n = 40) and the OCP Group ( n = 40). Although \nseven patients in the Dienogest group reported adverse \nevents related to breakthrough bleeding and menstrual \nirregularities, all patients were adherent to their treat -\nment plans and completed the 24-week follow-up period \nwith no dropouts or treatment discontinuation. Fig.  1 \nillustrates the study flow chart of enrolled patients and \nreasons for exclusion. The baseline demographic and \nclinical characteristics were comparable between the \ntwo groups, with no statistically significant differences \nobserved for any variable (Table  1). The mean age was \n34.3 ± 6.9 years in the Dienogest group and 32.5 ± 7.6 \nyears in the OCP group ( P = 0.28). Similarly, there was no \nsignificant difference in BMI (P = 0.8), gravidity (P = 0.17), \nparity ( P = 0.13), history of infertility (15% vs. 20%, \nP = 0.55), or previous CS history (40% vs. 45%, P = 0.65).\nBaseline endometriosis pain and clinical scores\nAt baseline, the severity of endometriosis-associated \npain and clinical signs, assessed using the Biberoglu \nand Behrman (B&B) score, was similar between the two \ntreatment groups (Table  2). There were no statistically \nsignificant differences in the distribution of severity for \npelvic pain ( P = 0.79), dysmenorrhea (P = 0.56), or dyspa-\nreunia ( P = 0.37). The mean total pelvic pain score (sum \nof pelvic pain, dysmenorrhea, and dyspareunia scores) \nwas 5.35 ± 2.04 in the Dienogest group and 5.47 ± 2.25 \nin the OCP group ( P = 0.79). Physical examination find -\nings, including pelvic tenderness ( P = 0.80) and indura -\ntion (P = 0.60), were also comparable, with a similar mean \ntotal physical sign score (3.52 ± 1.4 vs. 3.27 ± 1.6, P = 0.47).\nChange in total symptoms and sign severity score (B&B \nScore)\nThe total symptoms and sign severity score demon -\nstrated a significantly greater improvement in the Dieno -\ngest group compared to the OCP group after 24 weeks \n\nPage 4 of 8\nAbdallah et al. Middle East Fertility Society Journal            (2025) 30:68 \nof treatment (Table  3). While baseline SSS scores were \nstatistically similar (Dienogest: 8.87 ± 3.3 vs. OCP: \n8.77 ± 3.6, P = 0.89), the endpoint SSS score was signifi -\ncantly lower in the Dienogest group (3.5 ± 2.4) than in the \nOCP group (4.95 ± 3.1), ( P = 0.02). The mean difference \n(reduction) in the SSS score was significantly larger in \nthe Dienogest group (5.3 ± 1.9) compared to the OCP \ngroup (3.82 ± 1.46), with a high degree of statistical sig -\nnificance ( P < 0.001). Correspondingly, the percentage \nTable 1 Comparison of the baseline characteristics between the study groups\nVariable Dienogest Group\n(N = 40)\nMean ± SD\nOCP Group\n(N = 40)\nMean ± SD\nP value\nAge 34.3 ± 6.9 32.5 ± 7.6 0.28\nBMI (kg/m 2) 21.9 ± 1.9 22.03 ± 0.2 0.80\nGravidity 2.75 ± 1.3 2.3 ± 1.5 0.17\nParity 2.35 ± 1.29 1.9 ± 1.3 0.13\nHistory of infertility** 6 (15%) 8 (20%) 0.55\nPrevious CS** 16 (40%) 18 (45%) 0.65\nSD standard deviation, BMI Body Mass Index, CS Cesarean Section, the difference was compared using independent t-test, Mann-Whitney U test, or Chi-square test \naccording to data type\nP value <0.05 is statistically significant *\nFig. 1 A flow chart illustrating patients’ enrollment in the study \n \n\nPage 5 of 8\nAbdallah et al. Middle East Fertility Society Journal            (2025) 30:68 \nof improvement was significantly higher for Dienogest \n(64.2 ± 20.3%) than for OCP (48.1 ± 23.5%), (P = 0.002).\nChange in health-related quality of life (EHP-30)\nThe overall health-related quality of life, as measured \nby the Endometriosis Health Profile-30 (EHP-30) total \nraw score (where lower scores indicate better health), \nshowed superior improvement in the Dienogest group \n(Table 4). Baseline scores were comparable (P = 0.74). The \nendpoint total score was significantly lower with Dieno -\ngest (39.0 ± 14.5) than with OCP (44.7 ± 17.9), ( P = 0.02). \nThe mean reduction in the EHP-30 total score was sig -\nnificantly greater in the Dienogest group (19.4 ± 9.1) \ncompared to the OCP group (12.25 ± 4.4), ( P < 0.001). \nThis also resulted in a significantly higher percent -\nage of change for Dienogest (33.6 ± 8.9%) versus OCP \n(22.6 ± 5.9%), (P < 0.001).\nEHP-30 pain scale items\nAnalysis of the EHP-30 pain subscale items at the study \nendpoint revealed a statistically significant benefit favor -\ning the Dienogest group across multiple domains related \nto daily life activities (Table  5). Compared to the OCP \ngroup, patients receiving Dienogest reported significantly \nless pain-related limitation for items including: being \nunable to go to social events ( P < 0.001), difficulty stand-\ning (P = 0.05), difficulty sitting ( P = 0.001), difficulty walk-\ning ( P = 0.04), difficulty with exercise ( P = 0.002), loss of \nappetite (P = 0.006), inability to sleep properly ( P = 0.01), \ninability to do desired activities ( P = 0.003), and feeling \nunable to cope with the pain ( P = 0.006). For example, \nTable 2 Comparison of endometriosis associated pelvic pain \n(Biberoglu and Behrman score) before treatment for each study \ngroup\nVariable Dienogest Group\n(N=40)\nN (%)\nOCP Group\n(N=40)\nN (%)\nP value\nPelvic pain (A)\n Mild 10 (25%) 11 (27.5%)\n Moderate 20 (50%) 17 (42.5%) 0.79\n Severe 10 (25%) 12 (30%)\nDysmenorrhea (B)\n Non 4 (10%) 4 (10%) 0.56\n Mild 11 (27.5%) 8 (20%)\n Moderate 19 (47.5%) 17 (42.5%)\n Severe 6 (15%) 11 (27.5%)\nDyspareunia (c)\n Non 2 (5%) 6 (15%) 0.37\n Mild 16 (40%) 11 (27.5%)\n Moderate 15 (37.5%) 17 (42.5%)\n Severe 7 (17.5%) 6 (15%)\nTotal pelvic pain score**\n Mean ±SD 5.35±2.04 5.47±2.25 0.79\nTotal pelvic pain score (A+B+C)\n Mild (1–3) 10 (25%) 10 (25%)\n Moderate (4–6) 21 (52.5%) 16 (40%) 0.41\n Severe (7–9) 9 (22.5%) 14 (35%)\nPelvic tenderness (D)\n Non 2 (5%) 4 (10%)\n Mild 9 (22.5%) 7 (17.5%) 0.80\n Moderate 18 (45%) 19 (47.5%)\n Severe 11 (27.5%) 10 (25%)\nInduration (E)\n Non 3 (7.5%) 7 (17.5%) 0.60\n Mild 17 (42.5%) 15 (37.5%)\n Moderate 14 (35%) 13 (32.5%)\n Severe 6 (15%) 5 (12.5%)\nTotal physical sign score**\n Mean ±SD 3.52±1.4 3.27±1.6 0.47\nTotal physical sign score (D+E)\n Non (0) 1 (2.5%) 3 (7.5%)\n Mild (1–2) 8 (20%) 9 (22.5%) 0.74\n Moderate (3–4) 23 (57.5%) 21 (52.5%)\n Severe (5–6) 8 (20%) 7 (17.5%)\n**difference was compared using independent t-test for continuous data ( **) \nand using Chi-square test for categorical variables\nP value <0.05 is statistically significant *\nTable 3 Comparison of endometriosis total symptoms and sign \nseverity score (Biberoglu and Behrman score) before and after \ntreatment for each study group\nVariable Dienogest Group\n(N=40)\nMean ±SD\nOCP Group\n(N=40)\nMean ±SD\nP value\nBaseline total SSS score\n Mean ±SD 8.87±3.3 8.77±3.6 0.89\nEndpoint total SSS score\n Mean ±SD 3.5±2.4 4.95±3.1 0.02*\nMean difference\n Mean ±SD 5.3±1.9 3.82±1.46 <0.001*\nPercentage of improvement\n Mean ±SD 64.2±20.3 48.1±23.5 0.002*\nSSS score Symptoms and sign severity score, the difference was compared using \nindependent t-test, Mann-Whitney U test, or Chi-square test according to data \ntype\nP value <0.05 is statistically significant *\nTable 4 Comparison of endometriosis health profile \nquestionnaire (EHP-30) total score before and after treatment for \neach study group\nVariable Dienogest \nGroup\n(N = 40)\nMean ± SD\nOCP Group\n(N = 40)\nMean ± SD\nP value\nBaseline EHP-30 total raw score 58.4 ± 20.5 56.9 ± 21 0.74\nEndpoint EHP-30 total score 39 ± 14.5 44.7 ± 17.9 0.02*\nMean difference 19.4 ± 9.1 12.25 ± 4.4 < 0.001*\nPercentage of change 33.6 ± 8.9 22.6 ± 5.9 < 0.001*\nEHP-30 Endometriosis Health Profile Questionnaire, the difference was \ncompared using independent t-test \nP value <0.05 is statistically significant *\n\nPage 6 of 8\nAbdallah et al. Middle East Fertility Society Journal            (2025) 30:68 \n85% of the Dienogest group reported being unable to \ngo to social events due to pain “Rarely” post-treatment, \ncompared to 45% of the OCP group (where 25% still \nreported “Sometimes”). Conversely, no significant dif -\nference was observed for “unable to do jobs around the \nhome” (P = 0.49) or “had to go to bed/lie down” (P = 0.14). \n(Table 5).\nDiscussion\nThe medical management of endometriosis-associated \npain requires treatments that are not only effective in \nsymptom reduction but also enhance the patient’s overall \nhealth-related QoL. This prospective cohort study com -\npared the efficacy of Dienogest and a combined OCP over \na 24-week period in women with histologically confirmed \nendometriosis. This study is one of the first prospective \ncohort analyses to directly compare the efficacy of Dieno-\ngest versus OCPs in managing endometriosis-associated \npain and QoL within a Middle Eastern population.\nFindings summary\nThe main statistically significant findings of this study \nconfirm the superior efficacy of Dienogest compared \nto OCP in treating endometriosis-associated pain and \nimproving QoL over 24 weeks: (1) Both groups showed \nsignificant improvement from baseline, but the Dieno -\ngest group achieved a significantly greater reduction in \nthe total symptoms and sign severity score compared to \nthe OCP group ( P < 0.001), (2) Dienogest resulted in a \nsignificantly greater reduction in dysmenorrhea (P = 0.04) \nand the total pelvic pain score ( P = 0.008) post-treatment, \n(3) The EHP-30 total score reduction was significantly \ngreater in the Dienogest group indicating a superior \nimprovement in overall QoL ( P < 0.001), and (4) Dieno -\ngest led to significantly less pain-related impairment \nacross multiple EHP-30 items related to daily activities, \nincluding social events, sitting, walking, exercise, and \nsleep quality (all P ≤ 0.05).\nOur results in the context of previous literature\nConsistent with the requirements for a robust compara -\ntive study, our Results revealed that both groups were \nwell-matched at baseline, showing no statistically sig -\nnificant differences in age, BMI, gravidity, parity, history \nof infertility, or previous Cesarean Section history (all P \n>0.05). This observation aligns closely with the findings \nof Mehdizadeh Kashi et al. [12], whose randomized study \nalso reported no significant demographic differences \nbetween women treated with Dienogest and a combined \noral contraceptive pill following laparoscopic surgery for \nsevere endometriosis.\nSimilarly, we established that both groups presented \nwith similar distributions in baseline pain parameters, \nincluding pelvic pain, dysmenorrhea, and dyspareu -\nnia (all P >0.05). The total pelvic pain and physical sign \nscores were also statistically similar. This finding is cor -\nroborated by Caruso et al. [13], who, in their comparative \nstudy of Dienogest and an estradiol/nomegestrol acetate \nTable 5 Comparison of endometriosis health profile questionnaire (EHP-30) for pain scale after treatment for each study group\nPain scale after Never Rare Sometimes Often Always P-value\nBeen unable to go to social events because of \nthe pain?\nDienogest 0 (0%) 34 (85%) 3(7.5%) 3(7.5%) 0 (0%) < 0.001*\nOCP 10(25% 18 (45%) 10(25%) 2(5%) 0 (0%)\nBeen unable to do jobs around the home \nbecause of the pain?\nDienogest 4 (10%) 20 (40%) 10(25% 3(7.5%) 3 (15%) 0.49\nOCP 2 (5%) 14 (35%) 16 (40%) 4 (10%) 4 (10%)\nFound it difficult to stand because of the pain? Dienogest 2 (5%) 24 (60%) 9 (22.5%) 4 (10%) 1 (2.5%) 0.05*\nOCP 0 (0%) 14 (35%) 16 (40%) 6 (15%) 4 (10%)\nFound it difficult to sit because of the pain? Dienogest 0 (0%) 30 (75%) 7 17.5%) 1 (2.5%) 2 (5%) 0.001*\nOCP 0 (0%) 14 (35%) 21 (52.5%) 5 (12.5%) 0 (0%)\nFound it difficult to walk because of the pain? Dienogest 4 (10%) 18 (45%) 10 (25%) 6(15%) 2(5%) 0.04*\nOCP 6 (15%) 14 (35%) 14 (35%) 0 (0%) 6(15%)\nFound it difficult to exercise or do the leisure ac-\ntivities you would like to do because of the pain?\nDienogest 4 (10%) 21 (52.5%) 6 (15%) 6 (15%) 3(7.5%) 0.002*\nOCP 0 (0%) 16 (65%) 21 (52.5%) 3(7.5%) 0 (0%)\nLost your appetite and/or been unable to eat \nbecause of the pain?\nDienogest 2 (5%) 22(55%) 10(25% 0 (0%) 6 (15%) 0.006*\nOCP 4(10%) 10(25% 20 (50%) 4 (10%) 2 (5%)\nBeen unable to sleep properly because of the \npain?\nDienogest 2 (5%) 26 (65%) 6 (15%) 2(5%) 4 (10%) 0.01*\nOCP 0 (0%) 20(50%) 16 (40%) 4 (10%) 0 (0%)\nHad to go to bed/lie down because of the pain? Dienogest 2(5%) 19 (47.5%) 13 (32.5%) 2(5%) 4 (10%) 0.14\nOCP 2(5%) 14 (35%) 20 (50%) 4 (10%) 0 (0%)\nBeen unable to do the things you want to do \nbecause of the pain?\nDienogest 2 (5%) 28 (70%) 4 (10%) 4 (10%) 2 (5%) 0.003*\nOCP 10 (25%) 16 (40%) 10 (25%) 0 (0%) 4 (10%)\nFelt unable to cope with the pain? Dienogest 0 (0%) 31(77.5%) 7 (17.5%) 0 (0%) 2 (5%) 0.006*\nOCP 2 (5%) 18 (45%) 18 (45%) 2 (5%) 0 (0%)\nP value <0.05 is statistically significant *, the difference was compared using the Chi-square test\n\nPage 7 of 8\nAbdallah et al. Middle East Fertility Society Journal            (2025) 30:68 \ncombined oral contraceptive, reported no significant dif -\nference in the severity of baseline pelvic pain, dysmenor -\nrhea, or dyspareunia.\nA key finding of our study is the superior efficacy of \nDienogest over OCP in reducing overall symptom bur -\nden. Dienogest showed a significantly greater reduc -\ntion in dysmenorrhea ( P = 0.04), the total pelvic pain \nscore ( P = 0.008), and the combined pain score severity \n(P = 0.01). Post-treatment, the OCP group had a higher \nproportion of moderate-to-severe pain remaining.\nThis result is partially consistent with Ebrahimpour \n[14], who reported that Dienogest showed a significant \nreduction in pelvic pain and dyspareunia ( P = 0.01), \nalthough OCP also showed a significant reduction \nin dyspareunia ( P = 0.01). The greater overall reduc -\ntion observed in our Dienogest group is supported by \nSutrisno & Firdaus’s meta-analysis [15], which concluded \nthat Dienogest substantially improved pelvic pain com -\npared to placebo. Our findings further differentiate the \nsuperior benefit of Dienogest when compared directly \nto OCPs over the study period. The greater clinical \neffectiveness of Dienogest translated into a significantly \ngreater improvement in the EHP-30 total raw score ( P \n= 0.02) and a larger mean improvement and percentage \nchange (both P < 0.001) compared to OCP .\nThis QoL finding, showing Dienogest superiority, con -\ntrasts with the conclusions of several previous studies. \nMehdizadeh Kashi et al. [ 12] reported that the mean \ndifference in the overall quality of life score before and \nafter intervention was similar between the Dienogest and \nCOCP groups (22 vs. 23.45 points), with no significant \ndifference observed between the intervention groups. \nSimilarly, Ebrahimpour [14] also found no significant dif-\nference between Dienogest and OCP groups regarding \nthe overall QoL score difference post-intervention. Our \nstudy’s divergence suggests that while both treatments \nyield improvement, the magnitude of the improvement \noffered by Dienogest (19.4 points mean reduction) ver -\nsus OCP (12.25 points mean reduction) is sufficient to \nreach statistical significance, possibly indicating a greater \nclinically meaningful benefit in our cohort. This finding is \nreinforced by the itemized EHP-30 analysis, which dem -\nonstrated that Dienogest significantly improved func -\ntional impairment across numerous daily activities.\nClinical implications\nThe superior efficacy of Dienogest in reducing overall symp-\ntom severity score and improving EHP-30 score has direct \nclinical implications. This enhanced efficacy may be linked \nto Dienogest’s unique mechanism of action, particularly \nits inhibitory effect on nerve growth factor (NGF) expres-\nsion. Given that NGF is a key mediator in generating the \nchronic pain associated with endometriosis, the targeted \naction of Dienogest provides a more specific and profound \nanti-nociceptive effect compared to the generalized hor -\nmonal suppression offered by OCPs. For patients struggling \nwith the chronic, disruptive nature of endometriosis-associ-\nated pain, the enhanced relief offered by Dienogest can lead \nto better daily functioning, improved participation in social \nlife, and better sleep quality. Therefore, it should be con -\nsidered the preferred first-line medical therapy for optimal \npain control, provided that clinicians and patients carefully \nweigh this benefit against the typically higher acquisition \ncost of Dienogest and the individual patient’s tolerance for \nits known potential side-effect profile. While OCPs remain \na viable and often cost-effective treatment option, our data \nsuggest that Dienogest should be considered the preferred \nfirst-line medical therapy for optimal pain control and maxi-\nmal quality of life restoration in women with endometriosis.\nStudy limitations\nDespite the strengths of this study, including its prospec -\ntive cohort design and the use of validated pain and QoL \nassessment tools, some limitations should be noted. First, \nour approach in calculating the required sample size was \nbased on a comparison between Dienogest and placebo \nwhich may not fully capture the true difference between \nthe two study groups. Second, this study focused solely \non efficacy outcomes (pain and QoL) and systematic data \ncollection for adverse events profiles was outside the \nscope of this 24-week study. Third, the requirement for a \nnormal BMI (< 25 kg/m2) restricted the study population \nto a specific, healthier weight group. While this helped \nto minimize confounding factors related to obesity and \nhormonal metabolism, it limits the generalizability of our \nfindings to the broader endometriosis population, which \nincludes women who are overweight or obese. Fourth, \nthe 24-week follow-up period may be insufficient to \nassess the long-term effects. Crucially, because outcomes \nwere only measured at the end of the treatment period, \nour study cannot assess the durability of pain relief or \ncompare the long-term recurrence rates following the \ncessation of Dienogest versus OCPs.\nConclusion\nBoth Dienogest and the combined oral contraceptive pill \nare effective in reducing endometriosis-associated pain \nand improving quality of life. However, Dienogest dem -\nonstrates superior efficacy in achieving greater reduc -\ntions in the total symptoms and sign severity score, \nspecific pain components like dysmenorrhea, and the \noverall EHP-30 score. These findings support the recom -\nmendation of Dienogest as a highly effective hormonal \nagent for the long-term management of symptomatic \nendometriosis.\nAcknowledgements\nNone to acknowledge.\n\nPage 8 of 8\nAbdallah et al. Middle East Fertility Society Journal            (2025) 30:68 \nAuthors’ contributions\n1. **Abdallah, M.:** investigation, data collection, formal analysis, writing. \n2. **Mohamed, A.S.:** methodology, resources, validation, writing, review, \nediting. 3. **Soliman, A.:** conceptualization, methodology, resources, review. \n4. **Tawfik. W.M.:** methodology, supervision, writing, review, editing.\nFunding\nNo funding sources.\nData availability\nData is provided upon reasonable request by contacting the corresponding \nauthor.\nDeclarations\nEthics approval and consent to participate\nThe study was conducted in accordance with the Helsinki Principles, and the \nstudy protocol was revised and approved by the ethical committee and the \ninstitutional research board under reference no. (MS-1-9-2025). All patients \nprovided informed written consent before enrollment.\nConsent for publication\nNot applicable.\nCompeting interests\nThe authors declare no competing interests.\nReceived: 14 October 2025 / Accepted: 29 November 2025\nReferences\n1. Grandi G, Xholli A, Napolitano A, Palma F, Cagnacci A (2015) Pelvic pain and \nquality of life of women with endometriosis during quadriphasic estradiol \nvalerate/dienogest oral contraceptive: a patient-preference prospective \n24-week pilot study. 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