Chronic low-grade inflammation and ovarian hypofunction: mechanisms and therapeutic perspectives

Chronic low-grade inflammation (CLI), a persistent and subtle inflammatory state, is increasingly recognized as a contributing factor in the pathogenesis of various diseases. Emerging evidence now implicates it in the decline of ovarian function. This review synthesizes recent findings on the interplay between CLI and female ovarian physiology, focusing on its mechanistic role in ovarian hypofunction (OH). We delineate four inflammatory mechanisms contributing to OH: (i) direct cytotoxic damage to ovarian tissue by pro-inflammatory cytokines; (ii) disruption of the ovarian follicular microenvironment; (iii) dysregulation of the hypothalamic-pituitary-ovarian (HPO) axis; and (iv) epigenetic modifications in germ cells mediated by inflammatory mediators. Building on this mechanistic framework, we explore the potential clinical utility of anti-inflammatory strategies for the prevention and treatment of OH. Finally, we review current and emerging options for immunomodulation and anti-inflammatory therapy, providing a perspective informed by current evidence for future clinical practice and research.