Santen Richard J, Pinkerton JoAnn V, Conaway Mark, Ropka Mary, Wisniewski Lisa, Demers Larry, Klein Karen O
Department of Medicine, Division of Endocrinology, University of Virginia Health Sciences Center, Charlottesville 22908, USA.
Menopause. 2002 May-Jun;9(3):179-87. doi: 10.1097/00042192-200205000-00006.
To determine the lowest dosage of vaginally administered estradiol (E2) that reverses signs and symptoms of urogenital atrophy but does not substantially increase plasma E2 levels.
Single-blind, single-arm study to determine the effects of de-escalating doses of vaginal estrogen on symptoms of urogenital atrophy, vaginal pH, and vaginal and urethral cytology. A questionnaire was used to assess subjective vaginal and urethral symptoms. Objective measurements included vaginal and urethral cytology, pH, endometrial biopsy, and 24-h circulating plasma luteinizing hormone, follicle-stimulating hormone (FSH), E2, and estrone levels obtained in a Clinical Research Unit. Circulating E2 levels were assayed with an ultrasensitive yeast bioassay with a detection limit of 0.02 pg/mL. Measurements were obtained over a 24-h period after administration of vehicle alone, on day 1 after the initial vaginal E2 dosage, after 3 weeks of daily E2 administration, and after an additional 9 weeks of twice weekly administration.
From the first seven subjects studied at a 10-microg dose of E2, 100% responded according to predefined criteria. Vaginal cytology showed statistical improvement at 3 and 12 weeks. Urethral cytology was statistically improved after 12 weeks. Vaginal pH decreased from postmenopausal to premenopausal levels at both 3 and 12 weeks. Eighty-two percent of symptoms were cured or improved. Endometrium remained atrophic. Circulating E2 levels remained within the postmenopausal range of 3-10 pg/mL.
A 10-microg dose of vaginal E2 effectively treated urogenital atrophy in seven women and did not cause endometrial hyperplasia or increase E2 levels.
确定经阴道给药的雌二醇（E2）能逆转泌尿生殖系统萎缩体征和症状但又不会显著提高血浆E2水平的最低剂量。
单盲、单臂研究，以确定递减剂量的阴道雌激素对泌尿生殖系统萎缩症状、阴道pH值以及阴道和尿道细胞学的影响。采用问卷调查评估主观的阴道和尿道症状。客观测量指标包括阴道和尿道细胞学检查、pH值、子宫内膜活检，以及在临床研究单元获得的24小时循环血浆促黄体生成素、促卵泡生成素（FSH）、E2和雌酮水平。采用检测限为0.02 pg/mL的超灵敏酵母生物测定法测定循环E2水平。在单独给予赋形剂后24小时内、首次阴道给予E2剂量后第1天、每日给予E2 3周后以及额外每周两次给予E2 9周后进行测量。
在最初以10微克剂量E2研究的前7名受试者中，100%根据预定义标准有反应。阴道细胞学检查在3周和12周时显示有统计学意义的改善。尿道细胞学检查在12周后有统计学意义的改善。阴道pH值在第3周和第12周时从绝经后水平降至绝经前水平。82%的症状得到治愈或改善。子宫内膜仍呈萎缩状态。循环E2水平保持在绝经后3 - 10 pg/mL范围内。
10微克剂量的阴道E2有效治疗了7名女性的泌尿生殖系统萎缩，且未引起子宫内膜增生或提高E2水平。
