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-μg 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-μg dose of vaginal E2 effectively treated urogenital atrophy in seven women and did not cause endometrial hyperplasia or increase E2 levels.
From the 1Departments of Medicine, 2Obstetrics and Gynecology and 3Health Evaluation Sciences, University of Virginia Health Sciences Center, Charlottesville, Virginia, USA; 4Departments of Pathology and Medicine, Pennsylvania State University School of Medicine, Hershey, Pennsylvania, USA; and 5University of California, San Diego, and Children's Hospital and Health Center, San Diego, California, USA.
Received July 17, 2001; revised and accepted October 16, 2001.
Address reprint requests to Richard J. Santen, MD, Department of Medicine, Division of Endocrinology, University of Virginia Health Sciences System, PO Box 800379, Charlottesville, VA 22908. E-mail: email@example.com.