Treatment of urogenital atrophy with low-dose estradiol: Preliminary results

Objective: 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. Design: 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. Results: 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. Conclusion: A 10-μg dose of vaginal E₂ effectively treated urogenital atrophy in seven women and did not cause endometrial hyperplasia or increase E₂ levels.