Lactoferrin as a non-hormonal therapeutic candidate for endometriosis.

Lactoferrin as a Non-Hormonal Therapeutic Candidate for Endometriosis: Mechanisms and Future Directions.

Akihiko Nakamura, Yoshihiro Tanaka, Akie Takebayashi, Tatsuro Amano, S Tsuji

Reprod Sci

Mar 31, 2026

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Abstract

The pathogenesis and progression of endometriosis may involve a complex combination of multiple factors, including chronic inflammation and oxidative stress. Hormonal therapy, the current standard for pharmacotherapy in endometriosis, causes various issues, such as restricting pregnancy during treatment and a high risk of recurrence after treatment discontinuation. This review investigates the use of lactoferrin (LF), a natural iron-binding glycoprotein, and outlines its mechanism of action, its potential as a non-hormonal therapeutic strategy, prospects for clinical application, and associated therapeutic issues. LF exerts anti-inflammatory, iron-chelating, antioxidant effects, and antiproliferative effects by suppressing signaling pathways and exhibits antifibrotic, antiangiogenic, and antibacterial properties. These are thought to be important physiological factors in endometriosis progression, for which LF exhibits a promising therapeutic candidate that could theoretically replace or complement hormone therapy. Observational studies have reported variations in serum and peritoneal fluid concentrations of LF and anti-LF antibodies in patients with endometriosis depending on the endometriosis stage, depicting LF as a potential therapeutic target. Furthermore, an in vitro study demonstrated that LF selectively induced cell cycle arrest in endometriotic stromal cells without affecting that of eutopic endometrial cells. Compared with other non-hormonal therapies, LF has an extremely lower risk of teratogenicity and fetal toxicity and could improve reproductive outcomes and perinatal prognosis, indicating its potential for continuous administration throughout various life stages. Further studies are needed to determine optimal administration routes and dosages for clinical applications.