Carlström K, Pschera H, Lunell N O
Department of Obstetrics and Gynaecology, Karolinska Institutet, Huddinge University Hospital, Sweden.
Maturitas. 1988 Dec;10(4):307-16. doi: 10.1016/0378-5122(88)90066-7.
Serum concentrations of 17 beta-oestradiol (E2), unconjugated oestrone (E1), total oestrone (tE1), progesterone (P), follicle-stimulating hormone (FSH) and sex-hormone-binding globulin (SHBG) were measured before and after daily intravaginal administration of 250 micrograms micronized E2 and 10 mg micronized P for 14 days to 12 post-menopausal and for 1 day only (during cycle days 5-8) to 11 pre-menopausal women. In the post-menopausal women the levels of all steroids increased to maximum values on day 1, 8-10 h after administration and fell thereafter. In the pre-menopausal women the steroid concentrations rose slowly to a plateau level 10-15 h after administration. Significantly higher absorption of E2 and E1 (area under the curve increments) was noted in the post-menopausal than in the pre-menopausal women. In the post-menopausal women the steroid levels measured on days 7 and 14 corresponded to those observed in the very early or late luteal phase. Area under the curve increments were usually smaller on days 7 and 14 than on day 1 and the absorption kinetics altered to a 'pre-menopausal' pattern. FSH levels were significantly reduced as from 12 h after administration on day 1 and onwards. A slight (10%) but significant increase in SHBG levels was noted on day 14. It was concluded that the combined E2 and P treatment used in this investigation brings about a physiological response with only minimal side effects on the liver as judged from changes in SHBG concentrations.
对12名绝经后妇女连续14天每天经阴道给予250微克微粉化雌二醇(E2)和10毫克微粉化孕酮(P),对11名绝经前妇女仅在月经周期第5 - 8天给予1天上述药物,分别于给药前后测定血清中17β - 雌二醇(E2)、未结合雌酮(E1)、总雌酮(tE1)、孕酮(P)、促卵泡激素(FSH)和性激素结合球蛋白(SHBG)的浓度。在绝经后妇女中,所有类固醇水平在给药后1天、8 - 10小时升至最高值,随后下降。在绝经前妇女中,类固醇浓度给药后10 - 15小时缓慢升至平台期水平。绝经后妇女中E2和E1的吸收(曲线下面积增加)显著高于绝经前妇女。在绝经后妇女中,第7天和第14天测得的类固醇水平与黄体早期或晚期观察到的水平相当。第7天和第14天的曲线下面积增加通常小于第1天,吸收动力学转变为“绝经前”模式。从给药后第1天12小时起,FSH水平显著降低。第14天SHBG水平有轻微(10%)但显著的升高。结论是,根据SHBG浓度变化判断,本研究中使用的E2和P联合治疗产生了生理反应,对肝脏的副作用最小。