title: Gynecologic effects of arzoxifene in postmenopausal women with osteoporosis or low bone mass.
abstract: OBJECTIVE
  The aim of this study was to report the gynecologic safety findings from the Generations trial, a phase 3 study of the selective estrogen receptor modulator (SERM), arzoxifene.
  
  
  METHODS
  A predefined objective of the trial was to evaluate the effects of arzoxifene on the genital tract. Gynecologic examinations were performed yearly, and further gynecologic assessment, including endometrial biopsy, was performed in a predefined subset of women and in those who developed vaginal bleeding.
  
  
  RESULTS
  Overall, 9,354 women were randomized (4,678 to placebo, 4,676 to arzoxifene 20 mg/d). There were 13 adjudicated cases of endometrial cancer (placebo, 4 cases; arzoxifene, 9 cases: P = 0.165) and 6 cases of endometrial hyperplasia (placebo, 2 cases; arzoxifene, 4 cases). Endometrial thickness, assessed at 24- and 36-month transvaginal ultrasounds in a subset of women, increased slightly in women assigned to arzoxifene compared with baseline and women in placebo. At the last measurement, 3 (1.7%) women assigned to placebo and 21 (10.2%) assigned to arzoxifene had an endometrial thickness greater than 5 mm (P < 0.001 for difference between treatment groups). Endometrial polyps were more common in women treated with arzoxifene (n = 37) than in women treated with placebo (n = 18; P < 0.05). Vulvular and vaginal inflammation, including mycotic infections, and vaginal discharge were reported more frequently in women treated with arzoxifene than in women treated with placebo, as were urinary tract infections.
  
  
  CONCLUSIONS
  Gynecologic events were generally more common in women treated with arzoxifene than in women treated with placebo. The gynecologic effects of arzoxifene seem to differ from those of raloxifene, although both SERMs have a benzothiophene structure. Although all SERMs influence cells through the estrogen receptor, they need to be evaluated independently in terms of their effects on various tissues, including the genital tract.
authors: New York University School of Medicine, New York, NY 10016, USA. steven.goldstein@med.nyu.edu
authors: Steven R
authors: SR
authors: Goldstein
authors: Harjit Pal
authors: HP
authors: Bhattoa
authors: Patrick
authors: P
authors: Neven
authors: David A
authors: DA
authors: Cox
authors: Sherie A
authors: SA
authors: Dowsett
authors: Jahangir
authors: J
authors: Alam
authors: Adrien
authors: A
authors: Sipos
authors: David
authors: D
authors: Muram
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016889:Endometrial Neoplasms / Q000453:epidemiology; D004717:Endometrium / Q000473:pathology; D005260:Female; D005831:Genital Diseases, Female / Q000139:chemically induced* / Q000453:epidemiology / Q000473:pathology; D006801:Humans; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy*; D010880:Piperidines / Q000009:adverse effects* / Q000627:therapeutic use; D010919:Placebos; D011127:Polyps / Q000453:epidemiology; D017698:Postmenopause; D020849:Raloxifene Hydrochloride / Q000009:adverse effects; D020845:Selective Estrogen Receptor Modulators / Q000009:adverse effects*; D013876:Thiophenes / Q000009:adverse effects* / Q000627:therapeutic use; D014592:Uterine Hemorrhage / Q000473:pathology; D014627:Vaginitis / Q000453:epidemiology; D014847:Vulvitis / Q000453:epidemiology
chemical_list: D010880:Piperidines; D010919:Placebos; D020845:Selective Estrogen Receptor Modulators; D013876:Thiophenes; D020849:Raloxifene Hydrochloride; C115121:LY 353381