Norethindrone Acetate vs Dienogest in Endometriosis Pain

Key Takeaways

• Both oral progestins were associated with significant pain-score reductions at follow-up, with no significant between-group difference in pain reduction.
• Norethindrone acetate was associated with a greater reduction in endometrioma size than dienogest, with p=0.037.
• Side-effect profiles were comparable, while 6-month dropout was higher with dienogest than norethindrone acetate at 47.5% versus 23.3% with p=0.026.

In a randomized trial of two oral progestins for endometriosis-associated pain, investigators found higher 6-month dropout with dienogest than norethindrone acetate, at 47.5% versus 23.3% (p=0.026). The single-center study randomized 70 patients and compared norethindrone acetate 5 mg daily with dienogest 2 mg daily over 12 months. Pain scores declined in both groups during follow-up, with no significant between-group difference in pain reduction. Pain findings were similar between groups, while retention and endometrioma outcomes differed.

This single-center, prospective, randomized trial enrolled 70 patients aged 18 to 40 years attending an Endometriosis Clinic from April 2022 through April 2023. Investigators randomly assigned 30 patients to norethindrone acetate 5 mg daily and 40 to dienogest 2 mg daily. Pain was assessed with a visual analog scale at baseline, 6 months, and 12 months. Dysmenorrhea, chronic pelvic pain, and endometrioma size were the main comparative outcomes.

Both groups showed significant reductions in pain scores at all follow-ups, and investigators did not detect a significant between-group difference in pain reduction. Baseline dysmenorrhea scores were 7.43 ± 2.9 with norethindrone acetate and 7.23 ± 2.87 with dienogest. By 12 months, dysmenorrhea scores were 0.00 ± 0.00 in both groups. Chronic pelvic pain scores at 12 months were 1.06 ± 2.43 with norethindrone acetate and 0.00 ± 0.00 with dienogest, with p=0.058, within an overall pattern of pain improvement in both groups.

For non-pain outcomes, norethindrone acetate was associated with a greater reduction in endometrioma size than dienogest, with p=0.037. Side-effect profiles were comparable between groups. At 6 months, 23 patients remained in the norethindrone acetate group and 21 remained in the dienogest group, while 16 and 18 completed treatment, respectively. Dropout at 6 months was higher with dienogest than norethindrone acetate, at 47.5% versus 23.3% (p=0.026).

The authors concluded that both progestins effectively reduced pain scores, while norethindrone acetate showed greater endometrioma reduction and lower dropout in this randomized comparison. They also suggested that the lower dropout with norethindrone acetate might relate to the higher dose, which remained the authors' interpretation. These findings are limited to this head-to-head study and its reported abstract outcomes.