Route-dependent endocrine and metabolic effects of estrogen replacement therapy

The route of estrogen replacement therapy has a major impact on the growth hormone (GH)-insulin-like growth factor-I (IGF-I) axis. Estrogen administra tion by the oral, but not the transdermal, route reduces IGF-I and increase s On levels in postmenopausal women. This perturbation of the GH-IGF-I axis occurs with different forms of estrogen treatment, indicating that the dis sociation of the somatotropic axis and concomitant increase in GH-binding p rotein levels are intrinsic effects of the oral route of estrogen administr ation. In clinical studies, oral estrogen reduced postprandial lipid oxidat ion, compared with transdermal estrogen, Oral estrogen was also associated with a reduction in lean body mass and an increase In fat mass, compared wi th transdermal estrogen, In contrast, the route of estrogen therapy had no impact on carbohydrate metabolism or the estrogen-induced increase in bone mineral density. The findings of route-dependent changes in body compositio n add a new dimension to health considerations concerning estrogen therapy in postmenopausal women and may have significant implications for estrogen replacement therapy in young hypogonadal females.