Design: Systematic review and meta-analysis

Setting: N/A

Patients or Participants: Online databases were searched from inception to October 2022 for observational and randomized-control trials (RCTs) reporting change in size of endometrioma following medical management.

Interventions: Following PRISMA guidelines, all English-language, full-text articles reporting change in endometrioma size (either diameter or volume) by US or MRI following medical therapy with any medication were included. Studies assessing recurrent cysts following surgical management were excluded. Risk of bias was assessed using the Cochrane Risk of Bias Tool for RCTs and Newcastle-Ottawa Scale for observational studies.

Measurements and Main Results: A total of 10,994 articles were identified, among which 34 were eligible for inclusion (observational n=30, RCT n=4). Studies primarily investigated dienogest (n=13, meta-analysis n=4), combined hormonal contraception (CHC) (n=11, meta-analysis n=6) and gonadotropin releasing hormone agonist (GnRH-a) (n=7, meta-analysis n=3) as medical therapies. Individually, all 34 studies reported a reduction in mean diameter, cyst volume, or both; however, this was not found to be statistically significant in meta-analysis of the following interventions: dienogest – effect size 0.94 (95% CI: 0.63-1.26, mean follow-up 21 weeks), CHC – effect size 2.59 (95% CI: -0.15-5.34, mean follow up 37.3 weeks), GnRH-a – effect size 3.24 (95% CI: -0.12-6.61, mean follow up 20 weeks). Other interventions identified in this review but not amenable to meta-analysis included norethindrone acetate (n=5), cabergoline (n=1), danazol (n=2), dydrogesterone (n=1), N-acetylcysteine (n=1), relugolix (n=2), levonorgestrel intrauterine system (n=1), and GnRH-a with aromatase inhibitor (n=1).

Conclusion: Although individual studies on various medical interventions report modest reduction in endometrioma size, the effect size was not statistically significant after meta-analysis of studies on dienogest, CHC, or GnRH-a – likely reflective of significant heterogeneity among included studies.