Pharmacotherapy of Endometriosis: Balancing of Safety, Efficacy, and Adherence to Treatment

The aim. To conduct a comprehensive analysis of the clinical and pharmacological efficacy of progestins (dydrogesterone, dienogest, and norethisterone acetate) for the treatment of endometriosis by systematizing data on their pharmacodynamic, pharmacokinetic characteristics, and safety profile to optimize the selection of a personalized therapeutic strategy. Materials and methods . The search of the literature was conducted regarding randomized controlled trials (RCTs), cohort studies, and meta-analyses for the period from 1958 to 2025 from the PubMed, Cochrane Library, and eLibrary.ru databases. Results . It was found that dienogest, dydrogesterone, and norethisterone acetate demonsrates comparable efficacy in reducing the intensity of endometriosis-associated pelvic pain. Dienogest showed efficacy comparable to gonadotropin-releasing hormone agonists with a better tolerability profile. Dydrogesterone exhibited the best safety profile with minimal impact on metabolic parameters. Norethisterone acetate showed efficacy comparable to dienogest, but with more pronounced androgenic effects. Key pharmacological features affecting the safety profile of drugs were identified, and the need for a personalized approach to the choice of therapy was justified. The main limitation is the insufficient number of direct comparative studies of various progestins. Conclusion. All the progestins considered are effective treatments for endometriosis, but have different safety profiles, which determines the need for individual drug selection, taking into account the patient’s characteristics and concomitant pathology. Promising areas for future research include conducting large multi-center RCTs, developing algorithms for personalized therapy selection, and studying the long-term effects of treatment.