Epidemiology, Genetic Etiology, and Intervention of Premature Ovarian Insufficiency

Ting Guo, Hongyuan Liu, Bingying Xu, Yu Qi, Keyan Xu, Xinyi Wu, Xinmiao He, Yingying Qin, Zi-Jiang Chen
Endocrine Reviews, First published online April 3, 2025, bnaf011
https://doi.org/10.1210/endrev/bnaf011

Abstract

Premature ovarian insufficiency (POI) is a highly heterogeneous reproductive disorder in both its etiology and clinical presentation. The epidemiological characteristics of POI suggest that its occurrence likely involves a combination of genetic and environmental factors. Deciphering the pathogenic mechanisms of POI is crucial for improving reproductive outcomes as well as managing the long-term complications associated with ovarian dysfunction. Recent studies expand the list of POI causal genes and promote the viability of genetic diagnosis. However, whole exome sequencing studies in large-scale POI cohorts and genome-wide association studies on the age at natural menopause have uncovered a complex genetic architecture underlying POI that includes monogenic and oligogenic inheritance modes, emphasizing the difficulties in genetic diagnosis, especially for the isolated cases. Moreover, our understanding of the physiology of ovarian aging has greatly benefited from recent advances in multiomics analysis, expanding our perspective on the pathogenic mechanisms and potential targeted therapeutic strategies for POI. In this review, we summarize the epidemiological characteristics of POI, as well as progress in genetic and epigenetic etiologies, and discuss advances in pharmacology and material science that will likely contribute to new interventions for ovarian aging. Finally, this review offers new insights into prospects for early diagnosis and treatment of POI, while identifying persistent challenges and potential solutions to be addressed through future research.

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