title: Treatment of urogenital atrophy with low-dose estradiol: preliminary results.
abstract: 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.
  
  
  METHODS
  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-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.
  
  
  CONCLUSIONS
  A 10-microg dose of vaginal E2 effectively treated urogenital atrophy in seven women and did not cause endometrial hyperplasia or increase E2 levels.
authors.affiliation: Department of Medicine, Division of Endocrinology, University of Virginia Health Sciences Center, Charlottesville 22908, USA. rjs5y@virginia.edu
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Santen
authors.forename: JoAnn V
authors.initials: JV
authors.lastname: Pinkerton
authors.forename: Mark
authors.initials: M
authors.lastname: Conaway
authors.forename: Mary
authors.initials: M
authors.lastname: Ropka
authors.forename: Lisa
authors.initials: L
authors.lastname: Wisniewski
authors.forename: Larry
authors.initials: L
authors.lastname: Demers
authors.forename: Karen O
authors.initials: KO
authors.lastname: Klein
mesh_terms: D000282:Administration, Intravaginal; D001284:Atrophy / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000008:administration & dosage* / Q000097:blood; D005260:Female; D052776:Female Urogenital Diseases / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D017698:Postmenopause; D016037:Single-Blind Method; D014566:Urogenital System / Q000473:pathology*; D014621:Vagina / Q000166:cytology / Q000378:metabolism; D014622:Vaginal Creams, Foams, and Jellies
chemical_list: D014622:Vaginal Creams, Foams, and Jellies; D004958:Estradiol