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Lipedema is a chronic, progressive disorder of adipose tissue that predominantly affects women, characterized by symmetrical fat accumulation in the extremities, pain, and resistance to caloric restriction. Recent insights suggest that lipedema represents a hormone-driven gynecological fat disorder, in which estrogen receptor (ER) imbalance plays a central role. The predominance of ERβ activity and suppression of ERα signaling are hypothesized to drive adipose hypertrophy, fibrosis, and inflammation, particularly in the context of intracrine estradiol excess. This model aligns lipedema with other estrogen-sensitive conditions, such as endometriosis and uterine fibroids, and provides a novel framework for understanding its pathophysiology. Therapeutically, this reframing opens new perspectives for hormonal modulation using selective progestins (drospirenone, gestrinone) and metabolic adjuncts such as tirzepatide, beyond the current symptomatic or surgical approaches.