Progesterone-Based Therapies for Endometriosis-Associated Pain: A Systematic Review and Meta-Analysis

Abstract

Inroduction: Endometriosis is a chronic, oestrogen-dependent inflammatory condition affecting approximately 10%–15% of women of reproductive age worldwide, representing one of the most significant gynaecological causes of pelvic pain and infertility. Progestins have been used as a cornerstone of medical management for over five decades, yet comparative evidence across individual agents remains heterogeneous. This systematic review and meta-analysis rigorously evaluates the efficacy and tolerability of progesterone-based therapies in reducing endometriosis-associated pelvic pain.Methods:A systematic literature search was conducted across MEDLINE, PubMed, Scopus, and Embase for English-language studies published between 2012 and 2023. Studies were screened using PRISMA guidelines. Nine studies meeting predetermined eligibility criteria were included in the meta-analysis. Risk of bias was assessed using the Cochrane Risk of Bias tool (RoB 2). Odds ratios (OR) and 95% confidence intervals (CI) were calculated for pain relief outcomes relative to adverse effects.Results: The nine included studies encompassed a range of progestin agents principally dienogest (2 mg/day), norethindrone acetate, and dydrogesterone  across study durations of 6 to 60 months. Eight of nine studies demonstrated a statistically significant positive association between progestin administration and pain relief. A strong positive association (OR range: 42.72–930.25) was identified in five studies. A moderate positive association (OR range: 6.87–27.91) was found in three studies. One study demonstrated a negative association (OR: 0.35), indicating a higher probability of adverse effects relative to pain relief.Conclusions: Progestin therapy particularly with dienogest and norethindrone acetate demonstrates robust and consistent efficacy in the management of endometriosis-associated pelvic pain. The heterogeneity across studies underscores the importance of individualised treatment selection. These findings provide a strong evidence base for the continued use of progestins as first- and second-line pharmacological therapy in endometriosis.