Sex Hormones in Lymphedema

SIMPLE SUMMARY: Lymphedema is a life-long disease that affects a large number of patients treated for breast-, gynecological-, and urologic cancers in Western countries. Given that hormone levels are strongly modified in these conditions, and that patients widely undergo through hormone therapy, it is tempting to speculate that hormones might be key regulators in the maintenance of lymphedema. Despite an obvious prevalence for women, the role of sex hormones and gender has been poorly investigated in this pathology. This review aims to decipher how sex hormones interact with lymphatic vessels and whether hormone therapy could participate in lymphedema development. ABSTRACT: Lymphedema is a disorder of the lymphatic vascular system characterized by impaired lymphatic return resulting in swelling of the extremities and accumulation of undrained interstitial fluid/lymph that results in fibrosis and adipose tissue deposition in the limb. Whereas it is clearly established that primary lymphedema is sex-linked with an average ratio of one male for three females, the role of female hormones, in particular estrogens, has been poorly explored. In addition, secondary lymphedema in Western countries affects mainly women who developed the pathology after breast cancer and undergo through hormone therapy up to five years after cancer surgery. Although lymphadenectomy is identified as a trigger factor, the effect of co-morbidities associated to lymphedema remains elusive, in particular, estrogen receptor antagonists or aromatase inhibitors. In addition, the role of sex hormones and gender has been poorly investigated in the etiology of the pathology. Therefore, this review aims to recapitulate the effect of sex hormones on the physiology of the lymphatic system and to investigate whetherhormone therapy could promote a lymphatic dysfunction leading to lymphedema.