Van Erpecum K J, Van Berge Henegouwen G P, Verschoor L, Stoelwinder B, Willekens F L
Department of Gastroenterology, University Hospital Utrecht, The Netherlands.
Gastroenterology. 1991 Feb;100(2):482-8. doi: 10.1016/0016-5085(91)90220-f.
Estrogen-replacement therapy is important for the prevention of postmenopausal osteoporosis. However, oral synthetic and conjugated estrogens increase biliary cholesterol saturation index and risk of gallstone disease. To examine whether transdermal estrogen administration could avoid these adverse effects, 17 postmenopausal women were treated with transdermal estradiol (Estraderm TTS; Ciba-Geigy, Arnhem, The Netherlands), 100 micrograms/day for 4 weeks, and after 1 month without therapy, with oral estradiol (Progynova; Schering, Weesp, The Netherlands), 2 mg/day for 4 weeks. The increase in the serum estradiol level was much higher during transdermal than oral estradiol administration. On the contrary, the increase in the serum estrone level was much more pronounced during oral treatment. Both modes of treatment led to a similar reduction of urinary calcium excretion. A highly significant decrease in serum phosphate levels was found during transdermal therapy. Biliary cholesterol saturation index did not change during transdermal therapy (mean +/- SEM, 1.25 +/- 0.06 before and 1.22 +/- 0.07 at the end of transdermal therapy; P = NS). A slight increase in cholesterol saturation index that did not reach statistical significance was found during oral therapy (1.28 +/- 0.09 before and 1.36 +/- 0.09 during oral treatment). However, the subgroup of women with strong increases in serum estrone levels during oral estradiol therapy (greater than 0.5 pmol/mL; n = 8) generally had increased biliary cholesterol saturation index, a decrease in relative percentage chenodeoxycholic acid in bile, and increased serum sex hormone-binding globulin levels during oral treatment. Cholesterol monohydrate crystals were never found in duodenal biles during either treatment. This study indicates that transdermal estradiol does not induce lithogenic bile. On the contrary, oral estradiol leads to lithogenic bile in a subgroup of women with strong increases in serum estrone levels during oral treatment.
雌激素替代疗法对于预防绝经后骨质疏松症很重要。然而，口服合成雌激素和结合雌激素会增加胆汁胆固醇饱和指数以及胆结石疾病的风险。为了研究经皮给予雌激素是否能避免这些不良反应，17名绝经后女性接受了经皮雌二醇（Estraderm TTS；瑞士汽巴 - 嘉基公司，荷兰阿纳姆）治疗，剂量为每日100微克，持续4周，在停药1个月后，又接受了口服雌二醇（Progynova；荷兰先灵公司，韦斯普）治疗，剂量为每日2毫克，持续4周。经皮给予雌二醇期间血清雌二醇水平的升高幅度远高于口服给药期间。相反，口服治疗期间血清雌酮水平的升高更为明显。两种治疗方式都使尿钙排泄量出现了类似程度的降低。经皮治疗期间血清磷酸盐水平出现了极显著下降。经皮治疗期间胆汁胆固醇饱和指数未发生变化（治疗前平均±标准误为1.25±0.06，经皮治疗结束时为1.22±0.07；P = 无显著性差异）。口服治疗期间发现胆固醇饱和指数有轻微升高，但未达到统计学显著性（口服治疗前为1.28±0.09，口服治疗期间为1.36±0.09）。然而，在口服雌二醇治疗期间血清雌酮水平大幅升高（大于0.5 pmol/mL；n = 8）的女性亚组中，口服治疗期间胆汁胆固醇饱和指数通常会升高，胆汁中鹅去氧胆酸的相对百分比会降低，血清性激素结合球蛋白水平会升高。两种治疗期间十二指肠胆汁中均未发现一水合胆固醇晶体。这项研究表明，经皮雌二醇不会诱发致石性胆汁。相反，口服雌二醇会在口服治疗期间血清雌酮水平大幅升高的女性亚组中导致致石性胆汁。
