Sexual dimorphism and estrogens in neuroendocrine neoplasms

Neuroendocrine neoplasms (NENs) belong to a heterogeneous group of tumors with diverse morphological and biological features. Evidence indicates that patients with NENs show sexual dimorphism, which may influence not only disease incidence but also its course and treatment response. The role of estrogens and estrogen receptors (ERs) has been extensively described in breast and endometrial cancer, although their importance in the pathophysiology of NENs remains poorly understood. In this review, we discuss current knowledge regarding the impact of estrogens and their receptors on the progression of NEN. We also elaborated the expression patterns of ERs in different NEN subtypes. Considering epidemiological differences between sexes, we analyze gender relationships in ER expression and NEN progression. Finally, we present available clinical data on the therapeutic potential of ER in NENs. Understanding estrogen roles in NENs may contribute to elucidate gender differences in the course of the disease and open the way to the design of new personalized therapies.