Norethindrone acetate versus dienogest for pain relief in endometriosis related pain: A randomized controlled trial

Abstract

Objective: To determine which progestin, norethindrone acetate (NETA) or dienogest, is more effective in alleviating pain associated with endometriosis?

Study design: This single-center, prospective, randomized trial included 70 patients aged 18-40 years attending the Endometriosis Clinic (April 2022-April 2023). Participants were randomly assigned to receive either NETA (5 mg daily) or dienogest (2 mg daily). Pain levels were assessed using a visual analog scale (VAS) at baseline and at 6- and 12-month follow-ups. Discontinuation rates, dropout reasons, and side effects were also recorded.

Results: The study included 70 patients, with 40 randomized to the dienogest group and 30 to the NETA group. Both groups showed significant reductions in pain scores at all follow-ups, with no significant differences between them. At baseline, dysmenorrhea scores were 7.43 ± 2.9 (NETA) and 7.23 ± 2.87 (dienogest). By 12 months, both groups had a dysmenorrhea score of 0.00 ± 0.00. Chronic pelvic pain scores improved to 1.06 ± 2.43 (NETA) and 0.00 ± 0.00 (dienogest) (p = 0.058). NETA demonstrated a significantly greater reduction in endometrioma size (p = 0.037). At the sixth month, there were 23 patients in the NETA group and 21 patients in the dienogest group, while 16 patients in the NETA group and 18 patients in the dienogest group completed the treatment. Side effect profiles were comparable; however, the dropout rate at six months was higher in the dienogest group (47.5 % vs. 23.3 %; p = 0.026).

Conclusions: Both progestins effectively reduced pain scores, but NETA achieved a greater reduction in endometrioma size and had a lower dropout rate, potentially due to its higher dose. These findings suggest NETA 5 mg/day may be a better approach instead of dienogest for the endometriosis treatment.

Trial registration number: International Clinical Trials Registry Platform No. NCT05476172.

Keywords: Chronic pelvic pain; Dienogest; Endometriosis; Norethindrone acetate; Progestin.