title: Effects of ospemifene on the female reproductive and urinary tracts: translation from preclinical models into clinical evidence.
abstract: OBJECTIVE
  Treatment of menopausal symptoms by compounds with tissue-selective estrogen agonist/antagonist effects, often called selective estrogen receptor modulators, has been researched as an alternative to the use of estrogen therapy. These structurally diverse molecules elicit tissue-dependent responses in hormone-responsive tissues and organs, exhibiting variations in estrogenic activity in preclinical models of postmenopausal reproductive tissues that may improve postmenopausal women's health (eg, prevention and treatment of breast cancer, osteoporosis, and vulvar and vaginal atrophy).
  
  
  METHODS
  This literature review investigates whether preclinical data predicted the clinical effects of ospemifene on female reproductive and urinary tract tissues and compares these findings with the specific vaginal effects of other estrogen receptor agonists/antagonists (tamoxifen, raloxifene, and bazedoxifene) in preclinical and clinical studies. Lasofoxifene, although not currently available, is included because of its unique effects on vaginal tissue.
  
  
  RESULTS
  The response of endometrial and vaginal tissues to estrogen receptor agonists/antagonists can be differentiated using transvaginal ultrasound, endometrial histopathology, cytologic examination of vaginal smears, assessment of physical changes in the vagina, and relief of symptoms associated with vulvar and vaginal atrophy (such as dyspareunia).
  
  
  CONCLUSIONS
  Available evidence indicates that ospemifene has unique effects on tissue, leading to a favorable long-term profile for the relief of vulvar and vaginal atrophy compared with other estrogen receptor agonists/antagonists (eg, tamoxifen, raloxifene, and bazedoxifene) with no short-term concerns about endometrial safety (based on endometrial hyperplasia, carcinoma, endometrial spotting, and endometrial bleeding).
authors.affiliation: From the 1Eastern Virginia Medical School, Norfolk, VA; 2University of Texas Southwestern Medical Center, Dallas, TX; 3University of Virginia, Charlottesville, VA; 4Yale School of Medicine, New Haven, CT; and 5Endorheum Consultants, Malvern, PA.
authors.forename: David F
authors.initials: DF
authors.lastname: Archer
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Carr
authors.forename: JoAnn V
authors.initials: JV
authors.lastname: Pinkerton
authors.forename: Hugh S
authors.initials: HS
authors.lastname: Taylor
authors.forename: Ginger D
authors.initials: GD
authors.lastname: Constantine
mesh_terms: D004965:Estrogen Antagonists / Q000494:pharmacology*; D005260:Female; D052776:Female Urogenital Diseases / Q000188:drug therapy; D006801:Humans; D008593:Menopause / Q000187:drug effects*; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000494:pharmacology; D057170:Translational Research, Biomedical; D014566:Urogenital System / Q000187:drug effects*
chemical_list: D004965:Estrogen Antagonists; D013629:Tamoxifen; C119141:Ospemifene