Insuficiência ovariana prematura: fatores causais e uma revisão da literatura

Abstract

Premature Ovarian Insufficiency (POI) is an endocrinometabolic condition characterized by the premature depletion of the ovarian follicular reserve before the age of 40, affecting approximately 1% of women of reproductive age. Conventional therapeutic interventions, such as hormone replacement therapy (HRT), alleviate the symptoms of hypoestrogenism and reduce the risk of associated comorbidities, including osteoporosis and cardiovascular diseases, but do not promote the restoration of gametogenesis or ovarian steroidogenesis. In the context of advanced therapies, gene therapy emerges as an innovative approach to correct pathogenic mutations associated with POI, restoring ovarian function through the editing or insertion of specific gene sequences. Preclinical studies in murine models have demonstrated the feasibility of genetic reprogramming in modulating gonadal function. However, challenges related to vectorization, biodistribution, and gene expression control still pose barriers to clinical translation. Simultaneously, regenerative medicine has been extensively investigated, with a focus on the therapeutic potential of mesenchymal stem cells (MSCs). Evidence suggests that MSCs, through paracrine mechanisms and interactions with the ovarian microenvironment, promote neoangiogenesis, follicular niche restoration, and the recovery of endocrine and reproductive function. Preliminary clinical trials indicate an improvement in ovarian response; however, aspects such as immunogenicity, the risk of tumorigenicity, and the standardization of cultivation and administration protocols require further investigation. Thus, although gene and cell therapies offer new therapeutic perspectives for POI, their clinical implementation requires robust translational studies to validate their long-term safety, efficacy, and feasibility.