L26/P-340 Comparative risks of dienogest versus medroxyprogesterone acetate in women with endometriosis and adenomyosis: a nationwide population-based cohort study

Abstract Study question To compare the risk of dienogest (DNG) with medroxyprogesterone acetate (MPA) for treating endometriosis and adenomyosis. Summary answer DNG demonstrates a significantly protective effect against gynecologic and hormone-related malignancies and disorders, and major adverse events (fracture and venous thromboembolism). What is known already DNG is a fourth-generation oral progestin with high affinity for progesterone receptors and is used to treat endometriosis and adenomyosis. MPA is an oral progestin that has been widely used in clinical practice because of its lower cost and widespread availability. However, real-world evidence comparing the risk profiles between DNG and MPA remains limited, particularly in patients with adenomyosis and endometriosis, and is further constrained in Taiwan by reimbursement policies that influence clinical decision-making. Study design, size, duration In this retrospective cohort study was conducted in Taiwan and used information collected from Taiwan Cancer Registry (TCR), TCR Long Form (TCRLF), the National Health Insurance Research Database (NHIRD), and the National Population Registry Data set from 2017 to 2020. Between 2017-2020, 195,748 diagnosed endometriosis and adenomyosis were included. The women were aged over 18 years and under 52 years. Participants/materials, setting, methods The propensity score match was conducted through logistic regression in a ratio of 1-to-1 to obtain a matched case with age variables. Student’s t-test and a chi-square test were used to compare the means and the proportions of demographic and outcome characteristics between the DNG, MPA and unexposed groups. All statistical analysis was performed using SAS version 9.4, and p-values < 0.05 were considered statistically significant. Main results and the role of chance A total of 96,916 patients (67.46%) with endometriosis and adenomyosis, were categorized into the unexposed group, and 46,738 patients (32.54%) were categorized into the exposed group. Among the exposed patients, 12,259 (26.23%) received MPA and 34,479 (73.77%) received DNG. To reduce potential bias arising from baseline differences, the propensity score match was conducted through logistic regression in a ratio of 1-to-1 to obtain a matched case with age variables. The incidence rate of endometrial intraepithelial neoplasia (EIN) (IRR 0.44; 95% CI:0.43-0.44), endometrial hyperplasia (IRR 0.34; 95% CI:0.32-0.36), endometrial cancer (IRR 0.37; 95% CI:0.37-0.38), ovarian cancer (IRR 0.52; 95% CI:0.51-0.53), and breast cancer (IRR 0.; 95% CI:0.87-0.89), Fracture (IRR 0.93; 95% CI:0.91-0.95), and venous thromboembolism (VTE) (IRR 0.88; 95% CI:0.87-0.89) were markedly lower in the DNG group compared to the MPA group. In contrast, the incidence rate of osteoporosis (IRR 1.22; 95% CI:1.21-1.23) was higher in the DNG group than in the MPA group. Overall, DNG was associated with a lower risk of most endometrial-related diseases and cancers. Limitations, reasons for caution The cohort study has a relatively short follow-up period of approximately four years, which may be insufficient to fully capture long-term outcomes. The reimbursement policy of the NHI in Taiwan may introduce a selection bias, as DNG requires additional diagnostic evaluation for reimbursement approval. Wider implications of the findings Our findings reveal a significant discrepancy between clinical guidelines and actual clinical practice, with over 99% of patients discontinuing progestin therapy within one year. Real-world data indicate that DNG may offer a more favorable long-term safety profile than MPA, potentially guiding individualized progestin choice in clinical practice Trial registration number No