Figure 1.

Schematic representation of the origin of E2 in women. A: In premenopausal women, E2 is produced by the ovary and acts as a circulating hormone. Therefore, circulating E2 is the driver of E2 action in peripheral tissues. B: In postmenopausal women, ovarian E2 production is abolished. E2 is synthesized locally in extraovarian tissues from an adrenal source of dehydroepiandrosterone (DHEA) and androstenedione (4A). The local precursor of E2 is E1 after aromatization from 4A. E2 is synthesized, acts, and is metabolized locally, and therefore circulating E2 is not a driver of E2 action. E2 could be a indirect biomarker of T2D risk in postmenopausal women. ESR, estrogen receptor.