title: Low-dose 17-β-estradiol cream for vaginal atrophy in a cohort without prolapse: Serum levels and vaginal response including tissue biomarkers associated with tissue remodeling.
abstract: OBJECTIVE
  Describe the effect of 50 mcg vaginal 17-β-estradiol (E2) cream on vaginal maturation, serum estrogen levels, atrophic symptoms, and biomarkers of oxidative stress and tissue remodeling in postmenopausal women without prolapse.
  
  
  METHODS
  Seventeen women, 65 years or older, applied intravaginal E2 cream nightly for eight weeks, then twice weekly for eight weeks. Vaginal biopsies, serial blood draws, and atrophic symptoms were obtained at baseline, eight, and sixteen weeks. Changes in atrophic symptoms, vaginal maturation indices (VMI), and serum E2 were measured. Immunohistochemical staining characterized levels of transforming growth factor-beta (TGF-β), nuclear factor kappa B (NFKB), inducible nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS), and thrombospondin (TSP).
  
  
  RESULTS
  Serum E2 levels (pg/ml) were unchanged from baseline (mean (SD)) 7.7 (3.3) to eight 9.7 (5.7) and sixteen 8.7 (5.8) (p=0.24) weeks. VMI (mean (SD)) improved from baseline 34.2 (18.3) to eight 56.7 (13.1) and sixteen 54.5 (11.3) (p<0.001) weeks with no difference between eight and sixteen weeks. Vaginal dryness (p=0.03) and itching (p=0.02) improved. Tissue biomarker levels did not change (TGF-β p=0.35, NFKB p=0.74, eNOS p=0.80, iNOS p=0.24, TSP p=0.80).
  
  
  CONCLUSIONS
  Vaginal E2 improved atrophic symptoms and VMI without elevating serum E2. Tissue remodeling biomarkers did not change.
authors.affiliation: Department of Obstetrics and Gynecology, University of Alabama at Birmingham, 1700 6th Ave S, Suite 10382, Birmingham, AL 35233, USA. Electronic address: janaillston@uabmc.edu.
authors.forename: Jana D
authors.initials: JD
authors.lastname: Illston
authors.affiliation: Department of Obstetrics and Gynecology, University of South Carolina School of Medicine Greenville, 890 W Faris Road, Suite 520, Greenville, SC 29605, USA.
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Wheeler
authors.affiliation: Department of Obstetrics and Gynecology, University of Alabama at Birmingham, 1700 6th Ave S, Suite 10382, Birmingham, AL 35233, USA.
authors.forename: C Richard
authors.initials: CR
authors.lastname: Parker
authors.affiliation: Department of Obstetrics and Gynecology, University of Alabama at Birmingham, 1700 6th Ave S, Suite 10382, Birmingham, AL 35233, USA.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Conner
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, 933 19th Street South, CH19-201, Birmingham, AL 35294, USA; Birmingham/Atlanta Geriatric Research, Education, and Clinical Center, Department of Veterans Affairs Birmingham VAMC, GRECC 11G 700 19th Street South, Birmingham, AL 35233, USA.
authors.forename: Kathryn L
authors.initials: KL
authors.lastname: Burgio
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, 933 19th Street South, CH19-201, Birmingham, AL 35294, USA; Birmingham/Atlanta Geriatric Research, Education, and Clinical Center, Department of Veterans Affairs Birmingham VAMC, GRECC 11G 700 19th Street South, Birmingham, AL 35233, USA.
authors.forename: Patricia S
authors.initials: PS
authors.lastname: Goode
authors.affiliation: Department of Obstetrics and Gynecology, University of Alabama at Birmingham, 1700 6th Ave S, Suite 10382, Birmingham, AL 35233, USA.
authors.forename: Holly E
authors.initials: HE
authors.lastname: Richter
mesh_terms: D000282:Administration, Intravaginal; D000368:Aged; D000369:Aged, 80 and over; D001284:Atrophy / Q000097:blood / Q000188:drug therapy / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D004958:Estradiol / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004967:Estrogens / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D017698:Postmenopause / Q000097:blood; D011391:Prolapse; D014621:Vagina / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014623:Vaginal Diseases / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D015415:Biomarkers; D004967:Estrogens; D004958:Estradiol
keywords: Estradiol; Tissue biomarkers; Vaginal atrophy; Vaginal estrogen