Aromatization of androgens in women: current concepts and findings.

OBJECTIVE To review the role of circulating C(19) steroids as precursors of estrogens in postmenopausal women. DESIGN Review of current published literature. RESULT(S) In postmenopausal women as in men, estradiol no longer functions as a circulating hormone, because it ceases to be formed by the ovaries at the time of menopause. Estradiol continues to be formed in a number of extragonadal sites, however, including breast, bone, vascular smooth muscle, and various sites in the brain. At these sites of formation, local estradiol levels can be quite high, but the production rate is insufficient to affect the body in a global fashion; thus, estrogen action at these extragonadal sites of synthesis is primarily at a local level and serves a paracrine or even intracrine role. Because of this, in postmenopausal women as in men, circulating estrogen levels do not drive growth and development of target tissues. Instead, they reflect the metabolism of estradiol at these extragonadal sites. Estrogen that is not metabolized at these sites reenters the circulation, and, consequently, circulating levels of estradiol reflect its synthesis and action in extragonadal sites. Thus, they are reactive instead of proactive. An important difference between estrogen production at these extragonadal sites and estrogen that is synthesized in the ovary is that the former is absolutely dependent on a supply of circulating C(19) androgenic substrate. CONCLUSION(S) Circulating levels of testosterone begin to decline in the mid-reproductive years, and the levels of adrenal androgenic steroids, namely adrostenedione and DHEA, decrease throughout postmenopausal life. Therefore, the circulating levels of these adrogenic steroids may serve an important role in the maintenance of local estrogen synthesis, for example, in the bone and brain where estrogen has a profound influence on the maintenance of mineralization on the one hand, and possible cognitive function on the other.