Women's health across the reproductive lifespan in women with germline TP53 pathogenic variants: a clinical perspective.

Li-Fraumeni syndrome, caused by germline TP53 pathogenic sequence variants (PSVs), is among the most penetrant hereditary cancer syndromes. With broader genetic testing and improved survivorship, more women with TP53 PSVs now seek reproductive and hormonal guidance throughout their lifespan. Yet, no evidence-based framework currently exists to support women's health care in this population. In this review, we searched the available literature and found an absence of data regarding contraception, fertility preservation, pregnancy, and menopause, resulting in inconsistent counseling and both under- and overtreatment. Drawing on analogies from other high-risk cancer syndromes and our multidisciplinary clinical experience, we present interim suggestions centered on shared decision-making, individualized hormonal management, and avoiding unnecessary interventions. These findings underscore the need for prospective studies and international registries to establish evidence-based and equitable women's health care for women with TP53 PSVs.