Hormonal Therapy and Peritoneal Cytokine Profiles in Stage III–IV Endometriosis: A Comparative Study of Combined Oral Contraceptives, Dienogest, and Leuprolide Acetate

Irwanto Thengkano; Sri Ratna Dwiningsih; Relly Yanuari Primariawan; Yetti Hernaningsih

doi:10.23750/abm.2026.18471

Authors

Irwanto Thengkano Department of Obstetrics and Gynecology, Dr. Soetomo General Academic Hospital, Faculty of Medicine, Universitas Airlangga,Surabaya https://orcid.org/0009-0006-5635-2306
Sri Ratna Dwiningsih Department of Obstetrics and Gynecology, Dr. Soetomo General Academic Hospital, Faculty of Medicine, Universitas Airlangga,Surabaya https://orcid.org/0000-0002-3952-2020
Relly Yanuari Primariawan Department of Obstetrics and Gynecology, Dr. Soetomo General Academic Hospital, Faculty of Medicine, Universitas Airlangga,Surabaya https://orcid.org/0009-0007-2682-0532
Yetti Hernaningsih Department of Obstetrics and Gynecology, Dr. Soetomo General Academic Hospital, Faculty of Medicine, Universitas Airlangga,Surabaya https://orcid.org/0000-0001-8773-8267

Keywords:

Endometriosis, hormonal therapy, peritoneal fluid, inflammatory cytokines, TNF-α, dienogest, leuprolide acetate

Abstract

Background and aim: Endometriosis is a chronic inflammatory disease characterized by ectopic endometrial tissue growth and persistent pelvic inflammation. Hormonal therapy is widely used in advanced disease; however, evidence regarding its differential effects on local peritoneal inflammatory cytokines remains limited. This study aimed to compare the effects of combined oral contraceptives (COCs), dienogest, and leuprolide acetate on peritoneal cytokine profiles in women with stage III–IV endometriosis.

Methods: This non-randomized comparative study included women with surgically confirmed stage III–IV endometriosis who received COCs, dienogest, or leuprolide acetate for 3–8 months prior to surgery, along with a control group without hormonal therapy. Peritoneal fluid samples were collected intraoperatively. Levels of tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) were measured using enzyme-linked immunosorbent assay. Group comparisons were performed using the Kruskal–Wallis test with post hoc analysis.

Results: Significant differences in peritoneal TNF-α levels were observed among groups (p = 0.023). Post hoc analysis showed significantly lower TNF-α levels in the COC and dienogest groups compared with controls (p = 0.004 and p = 0.041, respectively). No significant differences were found in peritoneal IL-1β or IL-6 levels.

Conclusions: Hormonal therapy was associated with differences in peritoneal TNF-α levels in women with advanced endometriosis, suggesting a modulatory effect on local inflammatory activity. COCs and dienogest were associated with lower peritoneal TNF-α concentrations compared with no hormonal treatment. These findings should be interpreted cautiously, as causal inference and clinical implications cannot be established from this study.

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