A comparative assessment of efficacy for pain relief and quality of life between dienogest and combined oral contraceptive pills in endometriosis patients in Eastern India

Manager Save my selection Original Article A comparative assessment of efficacy for pain relief and quality of life between dienogest and combined oral contraceptive pills in endometriosis patients in Eastern India Department of Obstetrics and Gynaecology, Institute of Postgraduate Medical Education and Research, Bhowanipore, West Bengal, India 1Department of Obstetrics and Gynaecology, RG Kar Medical College and Hospital, Kolkata, West Bengal, India Address for correspondence: Dr. Rathindra Nath Ray, Department of Obstetrics and Gynaecology, Institute of Postgraduate Medical Education and Research, Bhowanipore, Kolkata 700020, West Bengal, India. E-mail:[email protected] This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License (http://creativecommons.org/licenses/by-nc-sa/4.0/), which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms. This study aimed to compare the effectiveness of dienogest (DNG) and combined oral contraceptive (COC) pills in alleviating pain among patients with endometriosis in Eastern India.

A prospective, hospital-based, observational comparative study was conducted at R. G. Kar Medical College and Hospital in Kolkata, India, from March 2021 to August 2022. The study included two groups: Group A (dienogest 2 mg/day, n = 115) and Group B (combined oral contraceptive pills, Mala-N, n = 115). Pain levels were assessed using the Visual Analog Scale (VAS), and the quality of life (QoL) was evaluated with the Endometriosis Health Profile Questionnaire (EHP-5 PRO) after 3 and 6 months of treatment.

The mean age ± standard deviation was 32.57 ± 8.02 years in Group A and 32.89 ± 7.92 years in Group B. After 6 months, Group A showed a significant reduction in pelvic pain (P = 0.001), whereas Group B did not experience a significant improvement (P = 0.55). A significant difference in pain reduction was observed between the two groups after 6 months (P = 0.0001). Both treatments resulted in slight improvements in the quality of life, but the difference between the groups was not statistically significant.

Both dienogest and COC pills may assist in managing endometriosis-related pain and enhancing the quality of life, with dienogest showing superior pain relief. These medications appear to be safe and effective options for managing endometriosis.

Endometriosis is a chronic gynecologic disorder that is characterized by the growth of endometrial-like tissue outside of the uterus and is associated with pelvic pain and infertility.[1] This disorder is an estrogen-dependent disease that affects 10%–15% of women of reproductive age, where the prevalence increases by about 70% with chronic pelvic pain.[2,3] Endometriosis can cause asymptomatic, acute, and chronic pelvic pain,[4] dyspareunia, dyschezia, chronic fatigue,[5,6] and infertility, which are the most common symptoms that have a significant effect on the quality of life (QoL) of patients with endometriosis.[4] According to the results of studies, 60%–70% of women with endometriosis suffer from some disorders, such as poor QoL, depression, and anxiety.[4-6] Unfortunately, due to the complexity and ambiguity of endometriosis, optimal control of symptoms, especially pain, is difficult and requires careful evaluation.[7,8] Therefore, the management of endometriosis-related pain may require several treatments.[8] Management of endometriosis is surgical (laparoscopy)[8,9] or medical (hormonal treatment, especially combined oral contraceptive pills or OCPs, progesterone, gonadotropin-releasing hormone, and antiprogesterone).[8,10] Several women take on-demand non-steroidal anti-inflammatory drugs (NSAIDs) as first-line therapeutic agents to control their pelvic pain.[11] The pelvic pain usually reappears when women discontinue their usage, thus affecting their quality of life (QoL). Moreover, women affected by chronic pelvic pain should use drugs with a continuous regimen, including hormonal contraceptives.[12,13] OCPs are one of the most common drugs for the treatment of endometriosis, also known as combined oral contraceptives (COCs). Despite their widespread use to manage symptoms and treat the disease, there are few clinical trials to confirm their effectiveness, and the evidence is largely based on observational studies.[14] In particular, studies involving OCPs have had difficulties with patient compliance and sample size, and in some studies, these treatments have been compared with other treatments.[15] It has been claimed that by reducing ovulation, OCPs temporarily suppress ectopic implants and reduce the inflammation and symptoms of pain caused by endometriosis.[14] Dienogest (DNG) is a synthetic progestin used in clinical treatments for endometriosis, administered at a daily dose of 2 mg.[13,16] The steroid also exhibits direct antiproliferative, immunologic, and antiangiogenic activities that help reduce endometriosis-associated symptoms, and it has highly selective binding to the progesterone receptor.[17,18] Many studies have reported that by reducing the size of endometriotic lesions, DNG has been able to alleviate the painful symptoms of endometriosis, which subsequently leads to an improvement in quality of life.[13,19-24] In this context, we attempted to determine the efficacy of pain relief between dienogest and combined oral contraceptive pills in endometriosis patients of eastern India.

Study design A prospective and hospital-based observational comparative study. Study area The study was conducted among outpatient attendees at the Department of Obstetrics and Gynaecology, R. G. Kar Medical College and Hospital, Kolkata, India. Duration of study This study was conducted over 18 months, from March 2021 to August 2022. Study population Patients confirmed or suspected of endometriosis on clinical evaluation and already prescribed for DNG and COCs by the Department of Obstetrics and Gynecology of R. G. Kar Medical College & Hospital, Kolkata, India. All of them are fulfilling the inclusion criteria. Sample size calculation and justification Our study required a sample size of 248 patients. Of them, 124 received dienogest, and another 124 received OCO pills. Significance Level (α) =5% Power (1-β)= 90% Projected true probability of success for COCs (p1)=50% In a study, Caruso[25] projected the true probability of success for Dienogest (p2) about 70% n1= Sample size for group 1 (Women receiving COCs). n2= Sample size for group 2 (Women receiving Dienogest). n1=[Z1−α/2p¯q¯(1+1k)+Z1−βp1q1+p2q2k]2△2 n2=kn1;k=1:1 where, q1=1−p1=0.5 q2=1−p2=0.3 △=|p1−p2|=0.2 p¯=p1+kp21+k=0.6 q¯=1−p¯=0.4 Z1−α/2=1.96 Z1−β=1.282 n1=[1.96×0.6×0.4(1+1)+1.282×0.5×0.5+0.7×0.3]20.04 n1=123.88≅124 n2=124 Total Sample size = 248 + 5% buffer. Finally, we selected the samples for comparative study with two groups: Group A: Women receiving dienogest (2 mg/day) of 115 nos. Group B: Women receiving OCO pills (Mala-N) of 115 nos. Inclusion criteria Patients confirmed or suspected of endometriosis on clinical evaluation (VAS score more than 5 and presence of subjective symptoms), surgical or imaging studies, and not taking any pain killer or other hormonal treatment for the moment, and who are receiving dienogest (2 mg/day). Age 20–45 years Regular menstrual cycles The presence of subjective symptoms during menstruation (at least one from among lower abdominal pain, lumbago, defecation pain, nausea, and headache) The presence of subjective symptoms during non-menstruation (at least one from among lower abdominal pain, lumbago, defecation pain, dyspareunia, and pain). Exclusion criteria Undiagnosed genital bleeding. A history of severe adverse drug reactions or hypersensitivity to steroid hormones. Having undergone surgery, therapy, or surgical examination for endometriosis within a menstrual cycle before the start of medication. Previous failure of treatment with the COCs used in the current study. Contraindications to COC or DNG use. Smokers >35 years. Age >45 years. A history of or complication of thrombosis/embolism. Migraines with aura. Depression. Patients on anti-epileptics. Diabetes mellitus with vascular involvement. Liver diseases. Known or suspected sex hormone-dependent malignancies. Repeat surgery for endometriosis. Patients consulting for infertility. Pregnant or nursing. Planning for pregnancy shortly. Study variables Patient demographics will be obtained at the time of inclusion. Age Parity Menstrual cycles History of any treatment for endometriosis Pain assessment (VAS score) BMI Educational qualifications Socioeconomic status Study tools used Case proforma sheets. Validated Questionnaire (EHP-5 PRO). Visual Analog Scale (VAS) sheet. Analysis of pain by visual analogue scale Analysis of quality of life (EHP-5 PRO) The Endometriosis Health Profile Validated Questionnaire (EHP-5 PRO) was administered at baseline and again at 3-month and 6-month intervals. How frequently have you experienced the following due to your endometriosis? Data collection and interpretation Data were collected through comprehensive history taking, clinical examination, and review of case sheets. These were documented in the case proforma and Bed Head Ticket (BHT). The collected information was then analyzed using appropriate statistical methods to identify correlations among various clinical findings. A schematic flowchart illustrating the study randomization process is presented in Figure 1. A schematic flow chart is exhibited for study randomization Following the application of exclusion criteria, eligible participants were enrolled. Two hundred and thirty women were recruited and divided evenly into two groups (Group A and Group B, each with 115 Nos). Inclusion was finalized after obtaining informed consent from each woman, following a detailed explanation, in her language, of the study’s purpose, procedures, and anticipated outcomes. After counseling, detailed medical histories were recorded for each participant. Statistical analysis For statistical analysis, symptom relief and treatment efficacy were assessed using a validated questionnaire during follow-up visits at 3 and 6 months. Data were entered into a Microsoft Excel spreadsheet and analyzed using IBM Statistical Package for the Social Sciences (SPSS) Statistics version 27.0 (Chicago, IL, USA) and GraphPad Prism version 5. Numerical variables were summarized as mean ± standard deviation, while categorical variables were presented as counts and percentages. Based on the data distribution, appropriate parametric or non-parametric tests were applied to compare outcome variables between the two groups. Independent samples (unpaired) were compared using the two-sample t test, while paired samples were analyzed using the paired t test, which offers greater statistical power. Categorical variables were compared using the chi-square test or Fisher’s exact test, as appropriate. An ANCOVA was conducted to compare group differences while controlling for covariates. A P value of ≤0.05 was considered statistically significant.

Table 1 compares baseline parameters between Group A and Group B. The mean age (± SD) of patients in Group A was 32.57 ± 8.02 years, while in Group B, it was 32.89 ± 7.92 years; this difference was not statistically significant (P = 0.761). Regarding education, most patients in Group A were graduates (46.08%), followed by those with primary education (20.86%). Similarly, in Group B, the highest proportion were graduates (35.65%), followed by those with primary education (23.47%). The distribution of educational levels between the two groups was not statistically significant (P = 0.243). Regarding the socioeconomic status, most patients in Group A belonged to the upper class (25.21%), followed by the upper lower and upper middle classes (each 20.86%). In contrast, Group B’s most common socioeconomic category was upper lower (23.47%), followed by lower class (22.60%). These differences were not statistically significant (P = 0.373). For the body mass index (BMI), the mean BMI in Group A was 27.01 ± 4.66 kg/m²; in Group B, it was 27.5 ± 4.8 kg/m², with no significant difference between the groups (P = 0.433). Regarding parity, most participants in Group A (74.78%) and Group B (78.26%) were multiparous, while nulliparous women comprised 25.22% and 21.74% of the groups, respectively. This difference was also statistically insignificant (P = 0.534). Lastly, a history of infertility was absent in most patients—97.39% in Group A and 98.26% in Group B—with no significant difference between the groups (P = 0.651). Table 2 presents a comparative analysis of pain-related parameters—including pelvic pain, dysuria, dyschezia, and dyspareunia—at baseline and 3-month and 6-month follow-up intervals for Groups A and B. Pain parameters of patients at baseline and follow-up visits In Group A, all pain parameters demonstrated statistically significant improvement at both the 3-month and 6-month follow-ups compared to the baseline. In contrast, in Group B, only dyspareunia demonstrated a statistically significant reduction at both follow-up points. When comparing the incidence and severity of pain in the two groups, pelvic pain showed a statistically significant difference after 6 months of treatment. Dyschezia exhibited a significant difference between the groups at 3 and 6 months. Dyspareunia showed a statistically significant difference only at the 6-month follow-up. Table 3 presents a comparative evaluation of quality of life domains—including pain, control and powerlessness, emotional well-being, lack of social support, and self-image—at baseline and 3-month and 6-month follow-up intervals for Groups A and B. Quality of life of patients at baseline and follow-up visits In Group A, only the pain domain showed a statistically significant improvement at 3 and 6 months compared to baseline. When comparing Groups A and B, a statistically significant difference was observed in the pain domain after 6 months of treatment.

Pain is the most prevalent symptom associated with endometriosis, with approximately 75% of symptomatic patients experiencing varying degrees of dysmenorrhea and pelvic discomfort. Despite the growing incidence of endometriosis in developing countries like India and its notable impact on women’s quality of life, few studies have been conducted in this context. Hence, this study aimed to compare the effectiveness of use of dienogest (DNG) and combined oral contraceptives (COCs) in pain relief. After 6 months of follow-up, Group A (DNG) showed a significant reduction in pelvic pain (P = 0.001), whereas Group B (COCs) demonstrated no significant improvement (P = 0.55). The difference between the two treatment groups at the 6-month mark was statistically significant (P = 0.0001), indicating that DNG was more effective than Mala-N in reducing pelvic pain in patients with endometriosis. Our findings align partially with those of Niakan et al.[25] who reported reductions in dysmenorrhea and pelvic pain in both treatment groups. However, they did not find a statistically significant difference between the two interventions, with 41.7% of patients showing pain improvement with DNG and 25% with OCPs. The study by Caruso et al.[26] demonstrated that DNG provided slight improvements in pelvic pain, dysmenorrhea, and dyspareunia over 3 months. Proponents of DNG treatment believe that since DNG contains no estrogen, it can be a good candidate for inhibiting the growth of endometriosis lesions and reducing the pain caused by endometriosis. They also suggested that progestin-only drugs may be a better intervention for endometriosis than estrogen–progestin contraceptive pills. It was observed that after 6 months of follow-up, group A showed a significant improvement in dysuria (P = 0.02). However, group B showed no significant improvement in dysuria (P = 0.12). There was no significant difference between DNG and OCPs (P = 0.259). There is a significant improvement in the dyschezia score in group A (P = 0.02). In contrast, there is no significant difference in group B (P = 0.38) after 6 months of follow-up; however, this difference is significant when comparing both groups (P = 0.001). In the case of dyspareunia, both groups A (P = 0.02) and group B (P = 0.01) showed significant improvement at the end of 6 months of treatment, and there was a significant difference between DNG and OCPs (P = 0.015). Niakan et al.[25] found a similar result after 12 weeks of administering DNG and OCPs, which mitigated the score of dyspareunia in both intervention groups compared to the placebo. This difference was not significant between the two groups. In the study by Brown et al.,[27] no difference was reported between OCPs and other treatments, and the researchers suggested that further studies are needed to evaluate the superiority of OCPs over other treatments. There was some improvement in the quality of life (QoL) of patients in group A after 6 months of intervention, primarily due to reduced pain while walking or performing duties at the workplace. A similar finding is consistent with those of previous studies conducted by Niakan et al.,[25] suggesting that DNG and OCPs effectively reduce pain associated with endometriosis. We observed no significant difference in the other four subscales (Control and Powerless, Emotional Well-being, Lack of Social Support, and Self-image) of quality of life between the two groups. Although DNG and OCPs slightly improved the quality of life (QoL) of women with endometriosis, there was no statistically significant difference between the two intervention groups. Researchers believe that the use of hormonal drugs can improve QoL by reducing dysmenorrhea, dyspareunia, and pelvic pain. Also, taking hormonal medications for 6 months usually leads to changes in the physical aspects and not the mental aspects of the QoL. Studies have shown that DNG consumption for 3 months led to a slight improvement in women’s quality of life. However, despite the positive evidence for the effect of OCPs on the QoL of women with endometriosis, the quality of studies in this area has been low. In addition, based on previous studies, it is impossible to conclude the relative superiority of OCPs over other treatments in improving quality of life. Techatraisak et al.[27] found that therapy with DNGt could improve health-related quality of life (HRQoL) and change the perception of EAPP in Asian women suffering from debilitating endometriosis symptoms. Drug-related side effects were generally tolerable, and the rate of discontinuation was null in both intervention groups. Combined estrogen-progestin oral contraceptives (COCs) have been the first-line of treatment for endometriosis for decades, although there has been insufficient evidence for their efficacy.

Women in Group A received Tab dienogest (2 mg daily), while those in Group B were administered Tab MALA-N (1 tablet daily) for 6 months. Assessments were conducted at baseline, 3 months, and the end of 6 months. After 6 months of follow-up, Group A showed significant improvement in pelvic pain, dysuria, dyschezia, and dyspareunia, whereas Group B did not demonstrate any significant improvement in these symptoms. No significant differences were observed between the groups in the other four quality-of-life subscales: control and powerlessness, emotional well-being, lack of social support, and self-image. The study suggests that both medications can be effectively used to manage pain associated with endometriosis without causing side effects. Ethical compliance statement The Institutional Ethics Committee (IEC) of the Department of Obstetrics and Gynaecology at R. G. Kar Medical College and Hospital, Kolkata, India, reviewed and approved the research protocol, deeming it appropriate for academic and clinical investigation. Approval to conduct the study was granted and formally communicated via Memo No. REC/281, dated February 22, 2021. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

1. Tsamantioti ES, Mahdy H. Endometriosis. Treasure Island (FL): StatPearls Publishing; 2025. Available from: https://www.ncbi.nlm.nih.gov/books/NBK567777/. [Last accessed on 10 Mar 2025]. 3. Eisenberg VH, Weil C, Chodick G, Shalev V. Epidemiology of endometriosis: a large population-based database study from a healthcare provider with 2 million members. BJOG 2018;125:55–62. 4. Kong S, Zhang YH, Liu CF, Tsui I, Guo Y, Ai BB, et al. Complementary and Alternative Medicine for Endometriosis: A Review of Utilization and Mechanisms. Evid Based Complement Alternat Med 2014;2014:146383. doi:. 5. Buggio L, Barbara G, Facchin F, Frattaruolo MP, Aimi G, Berlanda N. Self-management and psychological-sexological interventions in patients with endometriosis: strategies, outcomes, and integration into clinical care. Int J Womens Health 2017;9:281–93. 6. Culley L, Law C, Hudson N, Denny E, Mitchell H, Baumgarten M, et al. The social and psychological impact of endometriosis on women’s lives: a critical narrative review. Hum Reprod Update 2013;19:625–39. 7. Deguara CS, Pepas L, Davis C. Does minimally invasive surgery for endometriosis improve pelvic symptoms and quality of life? Curr Opin Obstet Gynecol 2012;24:241–4. 12. Muzii L, Di Tucci C, Achilli C, Di Donato V, Musella A, Palaia I, et al. Continuous versus cyclic oral contraceptives after laparoscopic excision of ovarian endometriomas: a systematic review and meta-analysis. Am J Obstet Gynecol 2016;214:203–11. 13. El Taha L, Abu Musa A, Khalifeh D, Khalil A, Abbasi S, Nassif J. Efficacy of dienogest versus combined oral contraceptive on pain associated with endometriosis: A randomized clinical trial. Eur J Obstet Gynecol Reprod Biol 2021;267:205–12. 14. Chapron C, Souza C, Borghese B, Lafay-Pillet MC, Santulli P, Bijaoui G, et al. Oral contraceptives and endometriosis: the past use of oral contraceptives for treating severe primary dysmenorrhea is associated with endometriosis, especially deep infiltrating endometriosis. Hum Reprod 2011;26:2028–35. 17. Okada H, Nakajima T, Yoshimura T, Yasuda K, Kanzaki H. The inhibitory effect of dienogest, a synthetic steroid, on the growth of human endometrial stromal cells in vitro. Mol Hum Reprod 2001;7:341–7. 18. Nakamura M, Katsuki Y, Shibutani Y, Oikawa T. Dienogest, a synthetic steroid, suppresses both embryonic and tumor cell-induced angiogenesis. Eur J Pharmacol 1999;386:33–40. 19. Römer T. Long-term treatment of endometriosis with dienogest: retrospective analysis of efficacy and safety in clinical practice. Arch Gynecol Obstet 2018;298:747–53. 21. Takagi H, Sakamoto J, Sasagawa T. Long-term treatment of endometriosis with dienogest for up to five years. Clin Exp Obstet Gynecol 2019;46:398–402. 22. Niakan G, Rokhgireh S, Ebrahimpour M, Kashi AM. Comparing the effect of dienogest and OCPS on pain and quality of life in women with endometriosis: A randomized, double-anonymized, placebo-controlled trial. Arch Iran Med 2021;24:670–7. 24. Sutrisno S, Firdaus WA. Efficacy of dienogest on pelvic pain and dyspareunia: A comprehensive meta-analysis and systematic review. Asian J Heal Res. 2023;2:89–95. 25. Niakan G, Rokhgireh S, Ebrahimpour M, Kashi AM. Comparing the effect of dienogest and OCPS on pain and quality of life in women with endometriosis: A randomized, double-blind, placebo-controlled trial. Arch Iran Med 2021;24:670–7. 26. Caruso S, Iraci M, Cianci S, Vitale SG, Fava V, Cianci A. Effects of long-term treatment with Dienogest on the quality of life and sexual function of women affected by endometriosis-associated pelvic pain. J Pain Res 2019;12:2371–8. 27. Techatraisak K, Hestiantoro A, Ruey S, Banal-Silao MJ, Kim MR, Seong SJ, et al. Effectiveness of dienogest in improving quality of life in Asian women with endometriosis (ENVISIOeN): interim results from a prospective cohort study under real-life clinical practice. BMC Womens Health 2019;19:68.