Efficacy of oral contraceptive pills versus dienogest on endometriosis pain scores: a prospective cohort study

Background Endometriosis is a chronic gynecological condition associated with pelvic pain, dysmenorrhea, dyspareunia, and impaired quality of life. Medical management aims to reduce symptoms and prevent recurrence. The primary objective of this study was to compare the efficacy of Dienogest versus Oral Contraceptive Pills (OCPs) in controlling endometriosis-associated pelvic pain. The secondary objective was to compare the improvement in health-related quality of life (QoL) between the two groups.

This prospective cohort study included 80 women with histologically confirmed endometriosis, divided in two groups. Group I (n = 40) received Dienogest 2 mg daily, and Group II (n = 40) received an OCP containing ethinyl estradiol 0.03 mg and drospirenone 3 mg daily for 24 weeks. The primary outcome was the change in endometriosis- associated pelvic pain from baseline to the end of treatment assessed using the total symptoms and sign severity score (Biberoglu and Behrman score).

Baseline demographic and clinical characteristics were similar between groups (p > 0.05). Both treatments significantly improved pelvic pain, dysmenorrhea, and dyspareunia (p < 0.001). However, Dienogest demonstrated greater reduction in total symptoms and sign severity scores (mean difference 5.3 vs. 3.82, p < 0.001) and higher percentage improvement (64.2% vs. 48.1%, p = 0.002). More patients in the Dienogest group shifted to mild/moderate severity (p = 0.04). EHP-30 scores showed significantly better post-treatment improvement with Dienogest (mean reduction 19.4 vs. 12.3, p < 0.001).

Both Dienogest and OCPs effectively reduce endometriosis-associated pain, but Dienogest provides superior improvement in symptom severity and quality of life, supporting its use as a more effective long-term therapeutic option.

Endometriosis, Dienogest, Oral contraceptive pills, Pelvic pain Efficacy of oral contraceptive pills versus dienogest on endometriosis pain scores: a prospective cohort study Mahmoud Abdallah1, Asmaa S. Mohamed2, Ahmed Soliman3* and Walid M. Tawfik1 Page 2 of 8 Abdallah et al. Middle East Fertility Society Journal (2025) 30:68

Endometriosis is a chronic disease that affects approxi - mately 10% of women of reproductive age [ 1]. Although endometriosis can be completely asymptomatic, acute and chronic pelvic pain, dysmenorrhea, dyspareunia, dyschezia, chronic fatigue, and infertility are the most common symptoms that have a significant effect on the quality of life (QOL) of patients. According to various studies, 60%–70% of women with endometriosis suffer from disorders such as poor QOL, depression, and anxi - ety [2]. Although the pathogenesis is enigmatic, endometriosis is characterized by lesions dependent on estrogen pro - duction, which promotes the proliferation and survival of endometrial tissue outside the uterus. The severity of the disease and associated pain is closely linked to the cyclic fluctuations of ovarian hormones, driving inflammation and lesion growth [3]. As a chronic and recurrent disease with an adverse effect on patients’ physical and psycho - logical well-being, it requires constant symptom control [4]. Medical management for endometriosis primarily uti - lizes hormonal therapies to create a hypoestrogenic envi - ronment and suppress the growth of ectopic endometrial lesions. These treatments include gonadotropin-releasing hormone (GnRH) agonists/antagonists, progestins, and combined oral contraceptive pills (OCPs) [ 5]. OCPs have long been a cornerstone of treatment, primarily working through pituitary suppression to inhibit ovulation and reduce endogenous estrogen levels, thereby causing atro - phy of the endometrial implants [6]. In addition to OCPs, another treatment that has been widely studied for the management of endome - triosis is Dienogest. Dienogest is a synthetic progestin, a 19-nortestosterone derivative, with good oral bioavail - ability and high selectivity for progesterone receptors. It has anti-ovulatory, antiproliferative, and inhibitory effects [ 7]. Dienogest has been shown to inhibit nerve growth factor expression induced by tumor necrosis fac - tor alpha or interleukin beta, a key mediator in generat - ing pain associated with endometriosis. Its inhibitory action exhibits a progestogenic response on endometrial stromal cells in vitro, such as decidualization, increased prolactin production, and growth retardation [ 7]. Unlike other progestins, Dienogest does not have androgenic properties, glucocorticoid activity, or mineralocorticoid activity. Several studies have shown a significant improve- ment in pain symptoms and quality of life following treat- ment with Dienogest [ 8, 9]. The primary objective of this study was to compare the efficacy of Dienogest with a commonly used oral contraceptive pill containing ethinyl estradiol and drospirenone for the control of endometri - osis-associated pelvic pain. The secondary objective was to compare the improvement in health-related quality of life, as assessed by the EHP-30, between the two treat - ment groups.

Study design and approval We conducted a prospective cohort study on patients with a histologically confirmed diagnosis of endome - triosis in the department of obstetrics and gynecology of Benha University Hospital from June 2024 to 2025. The study was conducted in accordance with the Hel - sinki Principles, and the study protocol was revised and approved by the ethical committee and the institutional research board under reference no. (MS-1–9−2025). All patients provided informed written consent before enrollment. Eligibility criteria Women aged between 18 and 50 years with a normal body mass index (BMI) of less than 25  kg/m 2, regular menstrual cycles, and symptomatic endometriosis with menstrual pain for more than 6 months. Exclusion cri - teria included pelvic pain originating from other organs (such as the gastrointestinal or genitourinary systems), a plan for pregnancy in the near future, use of gonado - tropin-releasing hormone (GnRH) analog treatment or other hormonal drugs within the last 3 months, the pres - ence of other gynecological diseases or malignancy, and any contraindications to OCPs or Dienogest use. Patients’ evaluation and grouping All eligible patients underwent a comprehensive evalu - ation at baseline, which included complete history tak - ing, physical examinations, and a series of investigational studies. A thorough physical examination was conducted to exclude systemic diseases and other sources of pain. Routine laboratory investigations were performed. A transvaginal ultrasound (TVS) using a 7.5  MHz vagi - nal probe was performed to specifically look for ovarian endometriomas. A systematic evaluation of the uterus and ovaries was carried out, including measurement of ovarian size in three orthogonal planes and assessment of ovarian mobility using gentle pressure. Patients were divided into two equal groups based on physician choice: Group A received Dienogest 2  mg tablet once daily for 24 weeks while Group B received 0.03 mg ethinyl estradiol combined with 3 mg drospire - none once daily for 24 weeks. Prior to the initiation of medical therapy, all patients underwent a standardized therapeutic laparoscopic procedure for definitive histo - logical diagnosis and surgical management. The medi - cal regimen was initiated in the first week following the procedure. Laparoscopy was performed under general anesthesia to allow for full visualization, definitive diagnosis, and Page 3 of 8 Abdallah et al. Middle East Fertility Society Journal (2025) 30:68 therapeutic management. Lesions suspicious for endo - metriosis were identified and biopsied using punch for - ceps. Biopsies were taken from all suspicious lesions, with histological confirmation being mandatory for study inclusion. The presence of lesions was mapped; however, anatomical severity was not formally categorized using the r-ASRM classification. The biopsy sites were coagu - lated by endocoagulation or bipolar coagulation. Patients with ovarian endometriomas were managed by cyst enu - cleation, followed by endocoagulation of the wound base (80 − 100 ∘C) and, when required, closure with endosu - tures using an extracorporeal knotting technique [ 10]. All biopsies were sent for histological confirmation of endometriosis. Study outcomes The primary outcome was the change in endometriosis- associated pelvic pain from baseline to the end of treat - ment assessed using the total symptoms and sign severity score (Biberoglu and Behrman score) (B&B) scale (a com- posite score derived from a 0–3 scale for dysmenorrhea, pelvic pain, dyspareunia, and palpation findings of ten - derness and induration). The pelvic pain score, ranging from 0 to 9, was based on the severity of pelvic discom - fort, dysmenorrhea, and dyspareunia. Pelvic pain was categorized as none (0), mild (1), mod - erate (2), or severe (3). Dysmenorrhea was rated from none (0) to severe (3, indicating incapacitation). Dyspa - reunia was similarly scored from none (0) to severe (3, indicating avoidance of intercourse). The physical sign score, ranging from 0 to 6, was based on assessments of pelvic tenderness and induration. The final total symp - tom and sign severity score, ranging from 0 to 15, was the sum of the pelvic pain score and the physical sign score, with categories ranging from none to very severe. Secondary outcomes include health-related quality of life evaluated at baseline and post-treatment using the validated EHP-30 which has scores ranging from 0 (best health status) to 100 (worst health status). Statistical analysis Data analysis was performed using SPSS version 26 (IBM Corp., Chicago, IL, USA). Parametric quantitative vari - ables were expressed as mean ± standard deviation (SD) and compared between groups using the unpaired Stu - dent’s t-test. Non-parametric quantitative variables were expressed as median and interquartile range (IQR) and analyzed using the Mann–Whitney U test. Categorical variables were expressed as frequency and percentage and analyzed using the Chi-square test or Fisher’s exact test as appropriate. A two-tailed p-value < 0.05 was con - sidered statistically significant. Sample size estimation GPower® version 3.1 was used for calculations of sample size, statistical calculator based on 95% confidence inter - val and power of the study 95% with α error 5%, and effect size of 0.56. According to a similar previous study [11], the mean pain score at the initial assessment was calculated as 8.40 ± 1.3 and decreased to 2.44 ± 2.1 at the three-month follow-up with using Dienogest therapy (p < 0.001). Based on this assumption and with dropout 10%, sample size was calculated according to these values pro - duced a samples size of 80 cases (40 cases for each group) to find such a difference.

Baseline demographic and clinical characteristics The study included 80 women with histologically con - firmed endometriosis, equally divided into the Dienogest Group ( n = 40) and the OCP Group ( n = 40). Although seven patients in the Dienogest group reported adverse events related to breakthrough bleeding and menstrual irregularities, all patients were adherent to their treat - ment plans and completed the 24-week follow-up period with no dropouts or treatment discontinuation. Fig.  1 illustrates the study flow chart of enrolled patients and reasons for exclusion. The baseline demographic and clinical characteristics were comparable between the two groups, with no statistically significant differences observed for any variable (Table  1). The mean age was 34.3 ± 6.9 years in the Dienogest group and 32.5 ± 7.6 years in the OCP group ( P = 0.28). Similarly, there was no significant difference in BMI (P = 0.8), gravidity (P = 0.17), parity ( P = 0.13), history of infertility (15% vs. 20%, P = 0.55), or previous CS history (40% vs. 45%, P = 0.65). Baseline endometriosis pain and clinical scores At baseline, the severity of endometriosis-associated pain and clinical signs, assessed using the Biberoglu and Behrman (B&B) score, was similar between the two treatment groups (Table  2). There were no statistically significant differences in the distribution of severity for pelvic pain ( P = 0.79), dysmenorrhea (P = 0.56), or dyspa- reunia ( P = 0.37). The mean total pelvic pain score (sum of pelvic pain, dysmenorrhea, and dyspareunia scores) was 5.35 ± 2.04 in the Dienogest group and 5.47 ± 2.25 in the OCP group ( P = 0.79). Physical examination find - ings, including pelvic tenderness ( P = 0.80) and indura - tion (P = 0.60), were also comparable, with a similar mean total physical sign score (3.52 ± 1.4 vs. 3.27 ± 1.6, P = 0.47). Change in total symptoms and sign severity score (B&B Score) The total symptoms and sign severity score demon - strated a significantly greater improvement in the Dieno - gest group compared to the OCP group after 24 weeks Page 4 of 8 Abdallah et al. Middle East Fertility Society Journal (2025) 30:68 of treatment (Table  3). While baseline SSS scores were statistically similar (Dienogest: 8.87 ± 3.3 vs. OCP: 8.77 ± 3.6, P = 0.89), the endpoint SSS score was signifi - cantly lower in the Dienogest group (3.5 ± 2.4) than in the OCP group (4.95 ± 3.1), ( P = 0.02). The mean difference (reduction) in the SSS score was significantly larger in the Dienogest group (5.3 ± 1.9) compared to the OCP group (3.82 ± 1.46), with a high degree of statistical sig - nificance ( P < 0.001). Correspondingly, the percentage Table 1 Comparison of the baseline characteristics between the study groups Variable Dienogest Group (N = 40) Mean ± SD OCP Group (N = 40) Mean ± SD P value Age 34.3 ± 6.9 32.5 ± 7.6 0.28 BMI (kg/m 2) 21.9 ± 1.9 22.03 ± 0.2 0.80 Gravidity 2.75 ± 1.3 2.3 ± 1.5 0.17 Parity 2.35 ± 1.29 1.9 ± 1.3 0.13 History of infertility** 6 (15%) 8 (20%) 0.55 Previous CS** 16 (40%) 18 (45%) 0.65 SD 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 according to data type P value <0.05 is statistically significant * Fig. 1 A flow chart illustrating patients’ enrollment in the study Page 5 of 8 Abdallah et al. Middle East Fertility Society Journal (2025) 30:68 of improvement was significantly higher for Dienogest (64.2 ± 20.3%) than for OCP (48.1 ± 23.5%), (P = 0.002). Change in health-related quality of life (EHP-30) The overall health-related quality of life, as measured by the Endometriosis Health Profile-30 (EHP-30) total raw score (where lower scores indicate better health), showed superior improvement in the Dienogest group (Table 4). Baseline scores were comparable (P = 0.74). The endpoint total score was significantly lower with Dieno - gest (39.0 ± 14.5) than with OCP (44.7 ± 17.9), ( P = 0.02). The mean reduction in the EHP-30 total score was sig - nificantly greater in the Dienogest group (19.4 ± 9.1) compared to the OCP group (12.25 ± 4.4), ( P < 0.001). This also resulted in a significantly higher percent - age of change for Dienogest (33.6 ± 8.9%) versus OCP (22.6 ± 5.9%), (P < 0.001). EHP-30 pain scale items Analysis of the EHP-30 pain subscale items at the study endpoint revealed a statistically significant benefit favor - ing the Dienogest group across multiple domains related to daily life activities (Table  5). Compared to the OCP group, patients receiving Dienogest reported significantly less pain-related limitation for items including: being unable to go to social events ( P < 0.001), difficulty stand- ing (P = 0.05), difficulty sitting ( P = 0.001), difficulty walk- ing ( P = 0.04), difficulty with exercise ( P = 0.002), loss of appetite (P = 0.006), inability to sleep properly ( P = 0.01), inability to do desired activities ( P = 0.003), and feeling unable to cope with the pain ( P = 0.006). For example, Table 2 Comparison of endometriosis associated pelvic pain (Biberoglu and Behrman score) before treatment for each study group Variable Dienogest Group (N=40) N (%) OCP Group (N=40) N (%) P value Pelvic pain (A) Mild 10 (25%) 11 (27.5%) Moderate 20 (50%) 17 (42.5%) 0.79 Severe 10 (25%) 12 (30%) Dysmenorrhea (B) Non 4 (10%) 4 (10%) 0.56 Mild 11 (27.5%) 8 (20%) Moderate 19 (47.5%) 17 (42.5%) Severe 6 (15%) 11 (27.5%) Dyspareunia (c) Non 2 (5%) 6 (15%) 0.37 Mild 16 (40%) 11 (27.5%) Moderate 15 (37.5%) 17 (42.5%) Severe 7 (17.5%) 6 (15%) Total pelvic pain score** Mean ±SD 5.35±2.04 5.47±2.25 0.79 Total pelvic pain score (A+B+C) Mild (1–3) 10 (25%) 10 (25%) Moderate (4–6) 21 (52.5%) 16 (40%) 0.41 Severe (7–9) 9 (22.5%) 14 (35%) Pelvic tenderness (D) Non 2 (5%) 4 (10%) Mild 9 (22.5%) 7 (17.5%) 0.80 Moderate 18 (45%) 19 (47.5%) Severe 11 (27.5%) 10 (25%) Induration (E) Non 3 (7.5%) 7 (17.5%) 0.60 Mild 17 (42.5%) 15 (37.5%) Moderate 14 (35%) 13 (32.5%) Severe 6 (15%) 5 (12.5%) Total physical sign score** Mean ±SD 3.52±1.4 3.27±1.6 0.47 Total physical sign score (D+E) Non (0) 1 (2.5%) 3 (7.5%) Mild (1–2) 8 (20%) 9 (22.5%) 0.74 Moderate (3–4) 23 (57.5%) 21 (52.5%) Severe (5–6) 8 (20%) 7 (17.5%) **difference was compared using independent t-test for continuous data ( **) and using Chi-square test for categorical variables P value <0.05 is statistically significant * Table 3 Comparison of endometriosis total symptoms and sign severity score (Biberoglu and Behrman score) before and after treatment for each study group Variable Dienogest Group (N=40) Mean ±SD OCP Group (N=40) Mean ±SD P value Baseline total SSS score Mean ±SD 8.87±3.3 8.77±3.6 0.89 Endpoint total SSS score Mean ±SD 3.5±2.4 4.95±3.1 0.02* Mean difference Mean ±SD 5.3±1.9 3.82±1.46 <0.001* Percentage of improvement Mean ±SD 64.2±20.3 48.1±23.5 0.002* SSS score Symptoms and sign severity score, the difference was compared using independent t-test, Mann-Whitney U test, or Chi-square test according to data type P value <0.05 is statistically significant * Table 4 Comparison of endometriosis health profile questionnaire (EHP-30) total score before and after treatment for each study group Variable Dienogest Group (N = 40) Mean ± SD OCP Group (N = 40) Mean ± SD P value Baseline EHP-30 total raw score 58.4 ± 20.5 56.9 ± 21 0.74 Endpoint EHP-30 total score 39 ± 14.5 44.7 ± 17.9 0.02* Mean difference 19.4 ± 9.1 12.25 ± 4.4 < 0.001* Percentage of change 33.6 ± 8.9 22.6 ± 5.9 < 0.001* EHP-30 Endometriosis Health Profile Questionnaire, the difference was compared using independent t-test  P value <0.05 is statistically significant * Page 6 of 8 Abdallah et al. Middle East Fertility Society Journal (2025) 30:68 85% of the Dienogest group reported being unable to go to social events due to pain “Rarely” post-treatment, compared to 45% of the OCP group (where 25% still reported “Sometimes”). Conversely, no significant dif - ference was observed for “unable to do jobs around the home” (P = 0.49) or “had to go to bed/lie down” (P = 0.14). (Table 5).

The medical management of endometriosis-associated pain requires treatments that are not only effective in symptom reduction but also enhance the patient’s overall health-related QoL. This prospective cohort study com - pared the efficacy of Dienogest and a combined OCP over a 24-week period in women with histologically confirmed endometriosis. This study is one of the first prospective cohort analyses to directly compare the efficacy of Dieno- gest versus OCPs in managing endometriosis-associated pain and QoL within a Middle Eastern population. Findings summary The main statistically significant findings of this study confirm the superior efficacy of Dienogest compared to OCP in treating endometriosis-associated pain and improving QoL over 24 weeks: (1) Both groups showed significant improvement from baseline, but the Dieno - gest group achieved a significantly greater reduction in the total symptoms and sign severity score compared to the OCP group ( P < 0.001), (2) Dienogest resulted in a significantly greater reduction in dysmenorrhea (P = 0.04) and the total pelvic pain score ( P = 0.008) post-treatment, (3) The EHP-30 total score reduction was significantly greater in the Dienogest group indicating a superior improvement in overall QoL ( P < 0.001), and (4) Dieno - gest led to significantly less pain-related impairment across multiple EHP-30 items related to daily activities, including social events, sitting, walking, exercise, and sleep quality (all P ≤ 0.05). Our results in the context of previous literature Consistent with the requirements for a robust compara - tive study, our Results revealed that both groups were well-matched at baseline, showing no statistically sig - nificant differences in age, BMI, gravidity, parity, history of infertility, or previous Cesarean Section history (all P >0.05). This observation aligns closely with the findings of Mehdizadeh Kashi et al. [12], whose randomized study also reported no significant demographic differences between women treated with Dienogest and a combined oral contraceptive pill following laparoscopic surgery for severe endometriosis. Similarly, we established that both groups presented with similar distributions in baseline pain parameters, including pelvic pain, dysmenorrhea, and dyspareu - nia (all P >0.05). The total pelvic pain and physical sign scores were also statistically similar. This finding is cor - roborated by Caruso et al. [13], who, in their comparative study of Dienogest and an estradiol/nomegestrol acetate Table 5 Comparison of endometriosis health profile questionnaire (EHP-30) for pain scale after treatment for each study group Pain scale after Never Rare Sometimes Often Always P-value Been unable to go to social events because of the pain? Dienogest 0 (0%) 34 (85%) 3(7.5%) 3(7.5%) 0 (0%) < 0.001* OCP 10(25% 18 (45%) 10(25%) 2(5%) 0 (0%) Been unable to do jobs around the home because of the pain? Dienogest 4 (10%) 20 (40%) 10(25% 3(7.5%) 3 (15%) 0.49 OCP 2 (5%) 14 (35%) 16 (40%) 4 (10%) 4 (10%) Found it difficult to stand because of the pain? Dienogest 2 (5%) 24 (60%) 9 (22.5%) 4 (10%) 1 (2.5%) 0.05* OCP 0 (0%) 14 (35%) 16 (40%) 6 (15%) 4 (10%) Found it difficult to sit because of the pain? Dienogest 0 (0%) 30 (75%) 7 17.5%) 1 (2.5%) 2 (5%) 0.001* OCP 0 (0%) 14 (35%) 21 (52.5%) 5 (12.5%) 0 (0%) Found it difficult to walk because of the pain? Dienogest 4 (10%) 18 (45%) 10 (25%) 6(15%) 2(5%) 0.04* OCP 6 (15%) 14 (35%) 14 (35%) 0 (0%) 6(15%) Found it difficult to exercise or do the leisure ac- tivities you would like to do because of the pain? Dienogest 4 (10%) 21 (52.5%) 6 (15%) 6 (15%) 3(7.5%) 0.002* OCP 0 (0%) 16 (65%) 21 (52.5%) 3(7.5%) 0 (0%) Lost your appetite and/or been unable to eat because of the pain? Dienogest 2 (5%) 22(55%) 10(25% 0 (0%) 6 (15%) 0.006* OCP 4(10%) 10(25% 20 (50%) 4 (10%) 2 (5%) Been unable to sleep properly because of the pain? Dienogest 2 (5%) 26 (65%) 6 (15%) 2(5%) 4 (10%) 0.01* OCP 0 (0%) 20(50%) 16 (40%) 4 (10%) 0 (0%) Had 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 OCP 2(5%) 14 (35%) 20 (50%) 4 (10%) 0 (0%) Been unable to do the things you want to do because of the pain? Dienogest 2 (5%) 28 (70%) 4 (10%) 4 (10%) 2 (5%) 0.003* OCP 10 (25%) 16 (40%) 10 (25%) 0 (0%) 4 (10%) Felt unable to cope with the pain? Dienogest 0 (0%) 31(77.5%) 7 (17.5%) 0 (0%) 2 (5%) 0.006* OCP 2 (5%) 18 (45%) 18 (45%) 2 (5%) 0 (0%) P value <0.05 is statistically significant *, the difference was compared using the Chi-square test Page 7 of 8 Abdallah et al. Middle East Fertility Society Journal (2025) 30:68 combined oral contraceptive, reported no significant dif - ference in the severity of baseline pelvic pain, dysmenor - rhea, or dyspareunia. A key finding of our study is the superior efficacy of Dienogest over OCP in reducing overall symptom bur - den. Dienogest showed a significantly greater reduc - tion in dysmenorrhea ( P = 0.04), the total pelvic pain score ( P = 0.008), and the combined pain score severity (P = 0.01). Post-treatment, the OCP group had a higher proportion of moderate-to-severe pain remaining. This result is partially consistent with Ebrahimpour [14], who reported that Dienogest showed a significant reduction in pelvic pain and dyspareunia ( P = 0.01), although OCP also showed a significant reduction in dyspareunia ( P = 0.01). The greater overall reduc - tion observed in our Dienogest group is supported by Sutrisno & Firdaus’s meta-analysis [15], which concluded that Dienogest substantially improved pelvic pain com - pared to placebo. Our findings further differentiate the superior benefit of Dienogest when compared directly to OCPs over the study period. The greater clinical effectiveness of Dienogest translated into a significantly greater improvement in the EHP-30 total raw score ( P = 0.02) and a larger mean improvement and percentage change (both P < 0.001) compared to OCP . This QoL finding, showing Dienogest superiority, con - trasts with the conclusions of several previous studies. Mehdizadeh Kashi et al. [ 12] reported that the mean difference in the overall quality of life score before and after intervention was similar between the Dienogest and COCP groups (22 vs. 23.45 points), with no significant difference observed between the intervention groups. Similarly, Ebrahimpour [14] also found no significant dif- ference between Dienogest and OCP groups regarding the overall QoL score difference post-intervention. Our study’s divergence suggests that while both treatments yield improvement, the magnitude of the improvement offered by Dienogest (19.4 points mean reduction) ver - sus OCP (12.25 points mean reduction) is sufficient to reach statistical significance, possibly indicating a greater clinically meaningful benefit in our cohort. This finding is reinforced by the itemized EHP-30 analysis, which dem - onstrated that Dienogest significantly improved func - tional impairment across numerous daily activities. Clinical implications The superior efficacy of Dienogest in reducing overall symp- tom severity score and improving EHP-30 score has direct clinical implications. This enhanced efficacy may be linked to Dienogest’s unique mechanism of action, particularly its inhibitory effect on nerve growth factor (NGF) expres- sion. Given that NGF is a key mediator in generating the chronic pain associated with endometriosis, the targeted action of Dienogest provides a more specific and profound anti-nociceptive effect compared to the generalized hor - monal suppression offered by OCPs. For patients struggling with the chronic, disruptive nature of endometriosis-associ- ated pain, the enhanced relief offered by Dienogest can lead to better daily functioning, improved participation in social life, and better sleep quality. Therefore, it should be con - sidered the preferred first-line medical therapy for optimal pain control, provided that clinicians and patients carefully weigh this benefit against the typically higher acquisition cost of Dienogest and the individual patient’s tolerance for its known potential side-effect profile. While OCPs remain a viable and often cost-effective treatment option, our data suggest that Dienogest should be considered the preferred first-line medical therapy for optimal pain control and maxi- mal quality of life restoration in women with endometriosis. Study limitations Despite the strengths of this study, including its prospec - tive cohort design and the use of validated pain and QoL assessment tools, some limitations should be noted. First, our approach in calculating the required sample size was based on a comparison between Dienogest and placebo which may not fully capture the true difference between the two study groups. Second, this study focused solely on efficacy outcomes (pain and QoL) and systematic data collection for adverse events profiles was outside the scope of this 24-week study. Third, the requirement for a normal BMI (< 25 kg/m2) restricted the study population to a specific, healthier weight group. While this helped to minimize confounding factors related to obesity and hormonal metabolism, it limits the generalizability of our findings to the broader endometriosis population, which includes women who are overweight or obese. Fourth, the 24-week follow-up period may be insufficient to assess the long-term effects. Crucially, because outcomes were only measured at the end of the treatment period, our study cannot assess the durability of pain relief or compare the long-term recurrence rates following the cessation of Dienogest versus OCPs.

Both Dienogest and the combined oral contraceptive pill are effective in reducing endometriosis-associated pain and improving quality of life. However, Dienogest dem - onstrates superior efficacy in achieving greater reduc - tions in the total symptoms and sign severity score, specific pain components like dysmenorrhea, and the overall EHP-30 score. These findings support the recom - mendation of Dienogest as a highly effective hormonal agent for the long-term management of symptomatic endometriosis.

None to acknowledge. Page 8 of 8 Abdallah et al. Middle East Fertility Society Journal (2025) 30:68 Authors’ contributions 1. **Abdallah, M.:** investigation, data collection, formal analysis, writing. 2. **Mohamed, A.S.:** methodology, resources, validation, writing, review, editing. 3. **Soliman, A.:** conceptualization, methodology, resources, review. 4. **Tawfik. W.M.:** methodology, supervision, writing, review, editing. Funding No funding sources. Data availability Data is provided upon reasonable request by contacting the corresponding author. Declarations Ethics approval and consent to participate The study was conducted in accordance with the Helsinki Principles, and the study protocol was revised and approved by the ethical committee and the institutional research board under reference no. (MS-1-9-2025). All patients provided informed written consent before enrollment. Consent for publication Not applicable. Competing interests The authors declare no competing interests. Received: 14 October 2025 / Accepted: 29 November 2025

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