Rodent models of functional hypothalamic amenorrhea: a systematic scoping review

Functional hypothalamic amenorrhea (FHA) is a complex clinical condition crucial to understand and treat due to its intricate etiology, difficulties in applying standard treatments, and significant long-term health effects. This study aimed to summarize and analyze the current research methodologies and findings from rodent models of FHA to provide insights for future investigations.

A literature search was conducted on EMBASE and MEDLINE up to September 23, 2022, using predefined search terms to target FHA-related studies in rodent models. This review focused on experimental studies involving rodent models of FHA, including related nonorganic disorders, such as primary ovarian insufficiency (POI) and polycystic ovary syndrome (PCOS). Data were independently collected by researchers, detailing animal models, FHA induction methods, experimental outcomes, and mechanistic exploration, with a synthesis of results comparing FHA with POI and PCOS.

Thirty articles (9 on FHA, 14 on POI, and 7 on PCOS) were analyzed, revealing diverse FHA induction methods, including dietary interventions and exercise, inconsistencies in estrous cycle monitoring, and varied focuses in mechanistic investigation. Some studies have emphasized hypothalamic-pituitary-adrenal axis dysfunction, whereas others have investigated ovarian abnormalities. Comparative analyses of POI and PCOS models identified research gaps and suggested future research directions.

The incorporation of consistent estrous cycle monitoring and biomarker measurements is crucial for the advancement of FHA research. Future studies should comprehensively investigate hormonal changes and explore potential therapeutic targets for ovarian inflammation and androgen involvement.