COMPARISON OF THE IMPACT OF TRANSDERMAL VERSUS ORAL ESTROGENS ON BILIARY MARKERS OF GALLSTONE FORMATION IN POSTMENOPAUSAL WOMEN

This prospective, randomized, double blind, parallel study was underta ken to elucidate further the potential mechanisms through which estrog ens could promote the formation of cholesterol gallstones and to compa re the impact of nonoral (transdermal) and oral estrogens on serum, he patic, and biliary markers of estrogen action. Ninety-seven postmenopa usal women were randomized to receive either transdermal estradiol (E- 2; 0.1 mg every 3.5 days; n = 48) or oral conjugated equine estrogens (1.25 mg every day; n = 49) for 8 weeks. Blood samples were drawn, and bile samples were obtained by cholecystokinin-stimulated duodenal dra inage before and after 8 weeks of estrogen administration. The main ou tcome measures included serum FSH, LH, E,, estrone, estrone sulfate, s ex hormone-binding globulin, lipid profiles, biliary cholesterol satur ation index, cholesterol nucleation time, presence of cholesterol crys tals in bile, as well as biliary arachidonate, PGE,, and mucous glycop roteins. Estrogens administered by both routes increased circulating e strogens and resulted in similar suppression of both gonadotropins. Se x hormone-binding globulin was clearly increased, and the changes in s erum lipids were more pronounced with oral conjugated equine estrogens than with transdermal E-2. The biliary cholesterol saturation index w as significantly increased compared to the baseline values with both t ransdermal E-2 (1.08 +/- 0.04 vs. 1.00 +/- 0.03; mean change, 8%) and oral conjugated equine estrogens (1.04 +/- 0.03 vs. 0.99 +/- 0.03; mea n change, 6%); however, there was no difference between the treatments . The number of patients with cholesterol crystals detected in bile wa s similar after both estrogen regimens. Transdermal and oral estrogens decreased nucleation time in vitro, increased arachidonate and PGE(2) levels, and minimally raised total glycoprotein concentrations. In co nclusion, transdermal and oral estrogens exerted comparable nonhepatic effects, as evidenced by similar reductions of gonadotropin levels, b ut oral therapy exhibited substantially greater actions on hepatic mar kers of estrogen action. Both transdermal E-2 and oral conjugated equi ne estrogens significantly elevated the biliary cholesterol saturation index and reduced the nucleation time. These results suggest that est rogens at the doses studied could promote gallstone formation by alter ation of biliary lipids and cholesterol nucleation time that have been incriminated in this process.