Dehydroepiandrosterone, androgens and the mammary gland

Mainly through the transformation of dehydroepiandrosterone (DHEA) into androgens in peripheral tissues by intracrine mechanisms, women synthesize at least two-thirds of the androgens found in men. Such data strongly suggest that androgens exert very important but so far underestimated physiological functions in women, including in the breast. In fact, the mammary gland possesses all the enzymatic machinery required to transform DHEA into both androgens and estrogens, although androgens are the predominant steroids synthesized from DHEA in the mammary gland. Early clinical studies have shown beneficial effects of androgens on breast cancer which are comparable to those observed with other hormonal therapies. In fact, a long series of preclinical and clinical data clearly indicate that proliferation of both the normal mammary gland and breast cancer results from the balance between the stimulatory effect of estrogens and the inhibitory effect of androgens. Moreover, the data showing the additive inhibitory effects of antiestrogens and androgens suggest that taking advantage of the inhibitory effect of androgens on breast cancer proliferation could well improve the efficacy of the currently used estrogen deprivation therapies for the treatment and prevention of breast cancer, the best and most physiological candidate being DHEA that limits the androgenic exposure to the tissues which possess the required enzymatic intracrine machinery.