Evaluation of Efficacy and Safety of 2 mg vs 4 mg Dienogest in Endometriosis: A Randomised Single-blind Dose-ranging Trial

Abstract

Introduction: Endometriosis is a recurring chronic inflammatory condition that affects females of reproductive age. Endometriosis-associated Pelvic Pain (EAPP) adversely impacts physical, mental, and social well-being. Currently, there is no ideal treatment option. Dienogest, a selective progestin, shows a pronounced effect on endometriosis. Aim: To compare the efficacy and safety of Dienogest at doses of 2 mg and 4 mg/day orally in the treatment of endometriosis. Materials and Methods: An observer-blind, parallel-group, randomised clinical trial was conducted in the Department of Obstetrics and Gynaecology at IPGME&R, SSKM Hospital, Kolkata, West Bengal, India, from April 2016 to December 2017. A total of 190 women aged 20-45 years suffering from endometriosis were recruited and divided into two treatment groups, A and B, receiving daily doses of 2 mg and 4 mg, respectively, for 24 weeks. Relief of EAPP was assessed using the Visual Analogue Scale (VAS) score, and improvement in Quality of Life (QoL) was measured. Treatment-related adverse events were also recorded. Numerical variables were compared using Student’s t-test or the Mann-Whitney U Test, and categorical variables were compared using the Chi-square test or Fisher’sexact test. Results: The absolute reduction in pelvic pain VAS score was 39.71±8.60 at 24 weeks from the initial score of 70.88 (Mean VAS score before treatment with Dienogest) in Group A, compared to 34.80±6.45 from 69.34 (Mean VAS score before treatment with Dienogest) in Group B (p=0.0001). The difference in mean VAS at 24 weeks between the two groups was statistically significant (p=0.0002). At 24 weeks, 18 (24.66%) patients in Group A experienced an irregular bleeding pattern compared to 27 (40.30%) in Group B, with spotting being the most common issue. Adverse effects such as weight gain, acne, alopecia, depression, and decreased libido were observed in both groups, but they were more pronounced in the 4 mg group. Conclusion: The efficacy and safety results from this doseranging study of Dienogest indicate that 2 mg/day is the effective dose for treating endometriosis and offers better tolerability compared to the 4 mg dose.