ORIGINAL RESEARCH article
Front. Endocrinol.
Sec. Translational and Clinical Endocrinology
This article is part of the Research TopicUtilizing Real-World Evidence for Better Endocrine Health ManagementView all 8 articles
Risks of Pelvic Inflammatory Disease and Bacterial Vaginosis in Adenomyosis Patients Using Levonorgestrel Intrauterine Device or Oral Norethindrone
Provisionally accepted
- 1Taichung Veterans General Hospital, Taichung, Taiwan
- 2National Yang Ming Chiao Tung University School of Medicine, Taipei City, Taiwan
- 3Chung Shan Medical University, Taichung, Taiwan
- 4HungKuang University College of Nursing, Taichung City, Taiwan
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Background Patients with adenomyosis frequently experience menorrhagia and dysmenorrhea. Levonorgestrel-releasing intrauterine device (LNG-IUD) and oral norethindrone are widely used non-surgical treatments options. However, their associated risks of pelvic inflammatory disease (PID) and bacterial vaginosis (BV) have not been well reported in the previous studies. Methods This multi-institutional retrospective analysis was performed using de-identified electronic health records from the TriNetX Research Network. Patients with adenomyosis treated with LNG-IUD or oral norethindrone were identified. A 1:1 propensity score matching (PSM) was conducted to control for potential confounding variables. Subgroup analysis was performed to evaluate outcomes of patients group with hemoglobin (Hb) ≥ 10 g/dL or Hb < 10 g/dL. Primary outcomes include risks of PID and BV. Secondary outcomes included risks of severe anemia (Hb < 10 g/dL), breast cancer, mood disorder, and cancer antigen 125 (CA-125) > 35 U/mL. Results After PSM, the LNG-IUD group showed a significantly lower risk of PID (Hazard ratio (HR) 0.545; 95% Confidence interval (CI) 0.483–0.616) and Hb < 10 g/dL (HR 0.850; 95% CI 0.775–0.932) compared to the oral norethindrone group. In contrast, the risk of BV was significantly higher in the LNG-IUD group (HR 1.223; 95% CI 1.116–1.342). No significant differences were observed between the two groups regarding associated breast cancer, mood disorder, or CA-125 ≥ 35 U/mL. Conclusion This study demonstrated that in patients with adenomyosis, treatment with LNG-IUD, compared to oral norethindrone, was associated with a lower risk of PID and severe anemia (Hb < 10 g/dL) but a higher risk of BV.
Keywords: Adenomyosis, Anemia, bacterial vaginosis, Levonorgestrel intrauterine device, Norethindrone, Pelvic Inflammatory Disease, Progesterone
Received: 11 Sep 2025; Accepted: 13 Nov 2025.
Copyright: © 2025 Niu, Yi, Shih and Tseng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Jenn-Jhy Tseng, tjj1018@gmail.com
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