State of the art endocrine treatments for patients diagnosed with endometrial cancer in 2025.

Purpose of review: Endometrial cancer (EC) is rising in incidence, particularly in younger, premenopausal women, due to increasing rates of obesity and delayed childbearing. This review evaluates current and emerging endocrine therapies, with a focus on fertility-preserving approaches for early-stage EC and treatment options for advanced or recurrent disease.

Recent findings: Fertility-sparing endocrine therapies, such as medroxyprogesterone acetate, megestrol acetate, and levonorgestrel-releasing intrauterine devices, achieve high response rates but carry recurrence risks. Biomarkers, including progesterone receptor status and molecular subtyping, are improving patient selection and outcomes. In advanced EC, single-agent and combination endocrine therapies with agents like selective estrogen receptor modulators, selective estrogen receptor down-regulators (SERDs), and aromatase inhibitors show efficacy, especially in hormone receptor-positive disease. Newer agents, including next-generation SERDs and proteolysis-targeting chimeras, hold potential for treating resistant cases.

Summary: Endocrine therapy offers a well tolerated alternative to chemotherapy in selected EC patients, particularly those with hormone-sensitive tumors. Advances in molecular profiling and the development of novel endocrine agents are refining treatment strategies, supporting endocrine therapy's continued role in managing EC across various stages.