Schubert W, Cullberg G
Department of Obstetrics and Gynecology, University of Gothenburg, Ostra Sjukhuset, Sweden.
Acta Obstet Gynecol Scand. 1988;67(3):271-5. doi: 10.3109/00016348809004218.
Eight ovariectomized women were given 0.5 mg 17 beta-estradiol cyclo-octyl acetate (E2COA) dissolved in arachis oil + 0.15 mg desogestrel, and 2 mg micronized 17 beta-estradiol (mE2) + 0.15 mg desogestrel orally in a crossover fashion for 20 days each. The preparations were taken on 10 days together with a meal, on 10 days 3 hours after a meal. Blood samplings were performed 3 h after capsule ingestion for analysis of serum estradiol (S-E2), estrone (S-E1) and sex hormone binding globulin (SHBG). Before treatment, all women had climacteric complaints. During treatment these symptoms were alleviated and no discomfort was reported. No differences in serum levels of estrogens were found in either of the preparations when capsules were taken with or without food. However, serum levels of E2 were found to be 100% higher per mg substance given after E2COA vis-à-vis mE2. This indicates either a delayed breakdown and/or a better resorption. The E1/E2 ratio after E2COA was only half that after mE2 intake. This hints at another route of resorption. SHBG concentrations were somewhat elevated following mE2 administration, whereas a slight decrease was found after E2COA. The resulting post-treatment difference was significant, suggesting a less estrogenic liver effect by E2COA. No accumulation of E2 or E1 was seen after either of the preparations. Our findings support the hypothesis that E2COA, being fat soluble, is resorbed via the lymphatic system. By avoiding the first liver pass the dosage of estrogen can be halved.
八名卵巢切除的女性以交叉方式接受治疗，每种制剂服用20天，其中一组服用溶解于花生油中的0.5毫克17β - 雌二醇环辛酯（E2COA）+ 0.15毫克去氧孕烯，另一组服用2毫克微粉化17β - 雌二醇（mE2）+ 0.15毫克去氧孕烯。制剂在10天与餐同服，在另外10天餐后3小时服用。在服用胶囊3小时后进行血样采集，以分析血清雌二醇（S - E2）、雌酮（S - E1）和性激素结合球蛋白（SHBG）。治疗前，所有女性均有更年期症状。治疗期间这些症状得到缓解，且未报告不适。无论胶囊与食物同服与否，两种制剂的血清雌激素水平均无差异。然而，相对于mE2，服用E2COA后每毫克物质的血清E2水平高出100%。这表明要么是分解延迟，要么是吸收更好。服用E2COA后的E1/E2比值仅为服用mE2后的一半。这暗示了另一种吸收途径。服用mE2后SHBG浓度有所升高，而服用E2COA后略有下降。治疗后产生的差异具有统计学意义，表明E2COA对肝脏的雌激素作用较小。两种制剂后均未观察到E2或E1的蓄积。我们的研究结果支持以下假设：E2COA由于脂溶性，通过淋巴系统吸收。通过避免肝脏首过效应，雌激素剂量可减半。
