Efficacy of transdermal XXXX .

@entity172 @entity1 @entity1641 @entity2082 @entity53
Several side effects and risks associated with @entity172 replacement therapy are known to stem from the hormone's impact on the liver. With oral administration, the enhanced action at hepatic, as compared with nonhepatic, sites is presumably related to the so-called first-pass effect. Attempts have been made to avoid this action by administering @entity172 nonorally, but heightened hepatic effects (comparable with those of other preparations) have nonetheless been seen with both @entity2082 and conjugated @entity1641 @entity172 given vaginally. We conducted a series of investigations aimed at evaluating the effects of @entity53 delivered via a transdermal patch. In a 50- @entity1 study of transcutaneous @entity53 (25, 50, 100, or 200 micrograms/day) versus placebo, a dose-dependent beneficial effect on objectively measured hot flashes was demonstrated. A second study was designed to compare the effects of these doses with those of 0.625 and 1.25 mg conjugated @entity1641 @entity172 administered orally. Effects on nonhepatic markers were similar for the 50 micrograms patch and 0.625 mg tablet, as well as for the 100 micrograms patch and 1.25 mg tablet. None of the doses of transdermal @entity53 exerted any measurable action on hepatic markers of @entity172 action, whereas both doses of conjugated @entity1641 @entity172 demonstrated actions on both hepatic protein and lipid synthesis. Our data clearly show that the transdermal administration of @entity53 circumvents the enhanced hepatic actions of the hormone. Possible explanations for these results are presented.
