Premature Ovarian Insufficiency (POI) refers to the failure of ovarian function in women before the age of 40. Although the etiology of most cases remains unclear, accumulating evidence indicates that chronic inflammation plays a key role in the occurrence and development of POI. Patients with POI often exhibit phenomena such as imbalance of pro-inflammatory cytokines, abnormalities in the local ovarian immune microenvironment, and autoimmune ovarian inflammation. Inflammation may accelerate ovarian function decline through mechanisms such as inducing follicular cell apoptosis, follicular atresia, and tissue fibrosis. Several studies have shown that anti-inflammatory interventions, such as immunosuppressants, can modulate ovarian inflammation and thereby improve ovarian function. Given the potentially central role of inflammation in POI, this review focuses on the interplay between inflammation and POI. We first delineate the mechanisms by which inflammation drives POI, cataloguing the autoimmune diseases and inflammation-related biomarkers implicated in its pathogenesis. Subsequently, we summarize recent findings from multiple POI animal models (natural aging, chemotherapy-induced, autoimmune, genetic) and highlight emerging therapeutic strategies that target inflammatory pathways. Given the pronounced etiological heterogeneity of POI, not all patients exhibit a distinctly enhanced inflammatory profile. Consequently, targeted anti-inflammatory interventions have yet to be routinely adopted in clinical practice, and their broad efficacy in reversing ovarian dysfunction requires robust validation in prospective human trials. Nevertheless, as the multifaceted role of inflammation-whether as a primary driver or a secondary consequence-becomes clearer, mechanistically targeted immunomodulation may offer promising new avenues for POI management.
Chen et al. (Fri,) studied this question.