Coelingh Bennink Herjan J T, Verhoeven Carole, Zimmerman Yvette, Visser Monique, Foidart Jean-Michel, Gemzell-Danielsson Kristina
1Pantarhei Bioscience BV, Zeist, The Netherlands 2University of Liège, Liège, Belgium 3Department of Women's and Children's Health, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
Menopause. 2017 Jun;24(6):677-685. doi: 10.1097/GME.0000000000000823.
Estetrol (E4) is an estrogen produced exclusively by the human fetal liver during pregnancy. In this study the pharmacodynamic effects of escalating doses of E4 in postmenopausal women were investigated.
This was a partly randomized, open-label, multiple-rising-dose study in 49 postmenopausal women. Participants were randomized to receive either 2 mg E4 or 2 mg estradiol-valerate (E2 V) for 28 days. Subsequent dose-escalation groups were (non-randomized): 10, 20 and 40 mg E4. Blood samples were collected regularly for measuring endocrine and hemostasis variables, lipids and lipoproteins, fasting glucose and bone turnover markers.
Estetrol treatment resulted in a decrease of follicle-stimulating hormone and luteinizing hormone and an increase of sex-hormone binding globulin. Changes in hemostasis variables were small. A lowering effect on low-density lipoprotein cholesterol was accompanied with an increase in high-density lipoprotein cholesterol and no or minimal changes in triglycerides. The considerable decrease in osteocalcin levels in the three highest E4 dose groups and the small decrease in C-telopeptide levels were comparable to the E2 V control group and suggest a preventive effect on bone loss. All changes observed were dose-dependent.
In this study, estetrol treatment showed dose-dependent estrogenic effects on endocrine parameters, bone turnover markers, and lipids and lipoproteins. The effect on triglycerides was small as were the effects on hemostatic variables. These results support the further investigation of estetrol as a candidate for hormone therapy. Quantitatively, the effects of 10 mg estetrol were similar to the study comparator 2 mg estradiol valerate.
雌三醇（E4）是孕期由人胎儿肝脏特异地产生的一种雌激素。本研究调查了绝经后女性中递增剂量E4的药效学作用。
这是一项针对49名绝经后女性的部分随机、开放标签、多剂量递增研究。参与者被随机分配接受2mg E4或2mg戊酸雌二醇（E2V）治疗28天。随后的剂量递增组（非随机）为：10mg、20mg和40mg E4。定期采集血样以测量内分泌和止血变量、脂质和脂蛋白、空腹血糖及骨转换标志物。
雌三醇治疗导致促卵泡激素和促黄体生成素水平降低，性激素结合球蛋白增加。止血变量变化较小。对低密度脂蛋白胆固醇有降低作用，同时高密度脂蛋白胆固醇增加，甘油三酯无变化或变化极小。三个最高E4剂量组骨钙素水平显著降低，C端肽水平略有降低，与E2V对照组相当，提示对骨质流失有预防作用。观察到的所有变化均呈剂量依赖性。
在本研究中，雌三醇治疗对内分泌参数、骨转换标志物以及脂质和脂蛋白显示出剂量依赖性雌激素效应。对甘油三酯的影响较小，对止血变量的影响也较小。这些结果支持进一步研究将雌三醇作为激素治疗的候选药物。从定量角度看，10mg雌三醇的效果与研究对照药物2mg戊酸雌二醇相似。
