硫酸δ-8-雌酮对绝经后女性的生物学效应。

Biologic effects of delta-8-estrone sulfate in postmenopausal women.

作者信息

Bhavnani B R, Cecutti A, Dey M S

机构信息

Department of Obstetrics and Gynecology, University of Toronto, Ontario.

出版信息

J Soc Gynecol Investig. 1998 May-Jun;5(3):156-60. doi: 10.1016/s1071-5576(98)00003-3.

DOI:10.1016/s1071-5576(98)00003-3

PMID:9614646

Abstract

OBJECTIVE

To determine in postmenopausal women the biological effects of delta-8-estrone sulfate, a novel estrogen component of Premarin (Wyeth-Ayerst, Philadelphia, PA).

METHODS

An open-label, nonrandomized study of six healthy postmenopausal women was conducted. Each subject took 0.125 mg of delta-8-estrone sulfate daily for 8 weeks. Blood samples were collected at day 0 (baseline) and once a week for 8 weeks. Urine was collected on day 0 and at weeks 2, 3, 5, 6, 7, and 8. Serum gonadotropins (follicle-stimulating hormone/luteinizing hormone), plasma binding proteins (corticosteroid-binding globulin/sex hormone-binding globulin), a marker for bone turnover (urinary n-telopeptide), and markers for cardiovascular effects (cholesterol, low-density lipoprotein, high-density lipoprotein(c), low-density lipoprotein oxidation, and rate of diene formation) were measured.

RESULTS

Follicle-stimulating hormone levels decreased from 84.0 +/- 8.5 to 67.0 +/- 8.5 mlU/mL (P = .02), whereas luteinizing hormone levels did not change. Corticosteroid-binding globulin levels increased from 3.30 +/- 0.16 to 4.10 +/- 0.16 mg/dL (P = .02), and no change in sex hormone-binding globulin was noted. The n-telopeptide levels decreased an average of 31% from 40.7 +/- 4.9 to 28 +/- 7.0 nmol/L bone collagen equivalents/mmol/L creatinine (P = .03). Plasma diene concentration and diene production rate decreased by 34% and 40%, respectively; these changes were not significantly different from baseline values. In contrast, a significant (P = .03) 68% increase in the lag time for low-density lipoprotein(c) oxidation (38.5 +/- 5.5 minutes versus 64.8 +/- 8.5 minutes) was observed. No significant change occurred in total cholesterol, high-density lipoprotein(c), and low-density lipoprotein(c).

CONCLUSION

Small doses (0.125 mg) of delta-8-estrone sulfate have profound estrogenic effects in postmenopausal women. The changes observed in n-telopeptide levels and the lag-time delay in oxidation of low-density lipoprotein(c) indicate that this estrogen contributes toward the overall beneficial effects on bone and cardiovascular system associated with Premarin therapy.

摘要

目的

确定硫酸δ-8-雌酮（倍美力（惠氏-艾尔斯特，宾夕法尼亚州费城）的一种新型雌激素成分）对绝经后女性的生物学效应。

方法

对6名健康绝经后女性进行了一项开放标签、非随机研究。每位受试者每天服用0.125mg硫酸δ-8-雌酮，持续8周。在第0天（基线）和之后的8周内每周采集一次血样。在第0天以及第2、3、5、6、7和8周收集尿液。检测血清促性腺激素（促卵泡激素/促黄体生成素）、血浆结合蛋白（皮质类固醇结合球蛋白/性激素结合球蛋白）、骨转换标志物（尿N-端肽）以及心血管效应标志物（胆固醇、低密度脂蛋白、高密度脂蛋白（c）、低密度脂蛋白氧化和二烯生成速率）。

结果

促卵泡激素水平从84.0±8.5降至67.0±8.5mIU/mL（P = 0.02），而促黄体生成素水平未发生变化。皮质类固醇结合球蛋白水平从3.30±0.16升至4.10±0.16mg/dL（P = 0.02），性激素结合球蛋白未见变化。N-端肽水平平均下降31%，从40.7±4.9降至28±7.0nmol/L骨胶原当量/mmol/L肌酐（P = 0.03）。血浆二烯浓度和二烯生成速率分别下降34%和40%；这些变化与基线值无显著差异。相比之下，观察到低密度脂蛋白（c）氧化的延迟时间显著增加（P = 0.03）68%（从38.5±5.5分钟增至64.8±8.5分钟）。总胆固醇、高密度脂蛋白（c）和低密度脂蛋白（c）无显著变化。