title: One-year long-term safety extension study of ospemifene for the treatment of vulvar and vaginal atrophy in postmenopausal women with a uterus.
abstract: OBJECTIVE
  The aim of this study was to assess the safety of ospemifene, a novel selective estrogen receptor modulator, for the treatment of vulvar and vaginal atrophy in postmenopausal women with a uterus.
  
  
  METHODS
  In this multicenter, randomized, double-blind, placebo-controlled, long-term safety extension study, nonhysterectomized women aged 40 to 80 years (n = 180) received daily oral doses of placebo, ospemifene 30 mg/day, or ospemifene 60 mg/day for 40 weeks (continued as blinded treatments from the initial 12-week pivotal efficacy study of ospemifene). The total treatment period was 52 weeks. Safety assessments included adverse events, cervical Papanicolaou tests, endometrial histology, endometrial thickness, gynecological examination, breast palpation, mammography, physical examination, and clinical safety laboratory assessments.
  
  
  RESULTS
  No clinically significant adverse changes in safety assessments were observed in any treatment group. Most treatment-emergent adverse events were mild or moderate in severity. Hot flushes, the most frequently occurring treatment-emergent adverse event related to the study drug, had a low discontinuation rate (1.6%). No study participants discontinued because of endometrial or cervical pathology; no endometrial findings were clinically meaningful. On week 52, more than 95% of endometrial biopsy samples either were classified as atrophic or inactive or had insufficient tissue for diagnosis. There were no treatment-emergent adverse events of pelvic organ prolapse or venous thromboembolism. No cases of endometrial hyperplasia or carcinoma were observed. Only three participants (1.7%) taking ospemifene experienced vaginal bleeding or spotting, which was self-limiting.
  
  
  CONCLUSIONS
  Daily doses of ospemifene 30 mg and ospemifene 60 mg yielded few treatment-emergent adverse events and demonstrated no significant endometrial changes during the 1-year treatment of vulvar and vaginal atrophy in postmenopausal women with a uterus.
authors.affiliation: Women's Health and Research Consultants, The George Washington University School of Medicine, Washington, DC 20036, USA. jsimon@JamesASimonMD.com
authors.forename: James A
authors.initials: JA
authors.lastname: Simon
authors.forename: Vivian H
authors.initials: VH
authors.lastname: Lin
authors.forename: Cathy
authors.initials: C
authors.lastname: Radovich
authors.forename: Gloria A
authors.initials: GA
authors.lastname: Bachmann
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001284:Atrophy / Q000188:drug therapy; D001706:Biopsy; D004311:Double-Blind Method; D004714:Endometrial Hyperplasia / Q000139:chemically induced; D004717:Endometrium / Q000473:pathology; D005260:Female; D006801:Humans; D008875:Middle Aged; D010919:Placebos; D017698:Postmenopause; D020845:Selective Estrogen Receptor Modulators / Q000627:therapeutic use*; D013629:Tamoxifen / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014621:Vagina / Q000473:pathology; D014626:Vaginal Smears; D014844:Vulva / Q000473:pathology
chemical_list: D010919:Placebos; D020845:Selective Estrogen Receptor Modulators; D013629:Tamoxifen; C119141:Ospemifene