title: Assessment of the safety of long-term bazedoxifene treatment on the reproductive tract in postmenopausal women with osteoporosis: results of a 7-year, randomized, placebo-controlled, phase 3 study.
abstract: OBJECTIVE
  To evaluate the clinical safety of bazedoxifene (BZA) on the reproductive tract in postmenopausal women with osteoporosis over 7 years.
  
  
  METHODS
  This was a second, blinded, 2-year extension of a 3-year, randomized, double-blind, placebo (PBO)- and active-controlled phase 3 trial. In the core study, subjects were randomized to receive BZA 20 or 40mg, raloxifene 60mg, or PBO. During years 4-5, the raloxifene arm was discontinued and subjects receiving BZA 40mg were transitioned to BZA 20mg. Subjects continued to receive BZA 20mg or PBO during years 6-7.
  
  
  METHODS
  The primary endpoint was the incidence of new vertebral fractures at 7 years (reported separately). Reproductive tract safety findings at 7 years are reported here. Endometrial thickness was assessed by transvaginal ultrasonography for subjects in the endometrial safety substudy. Adverse events (AEs) were recorded throughout the study.
  
  
  RESULTS
  At 7 years, the adjusted mean (±standard error) change in endometrial thickness was similar with BZA and PBO (-0.11 ± 0.21 and 0.07 ± 0.32 mm, respectively). The incidence of endometrial hyperplasia was low (0.1% for both groups). BZA showed significantly lower rates than PBO of endometrial carcinoma (0.1% vs. 0.4%; P=0.020) and vaginitis (6.1% vs. 7.6%; P=0.035). There were more cases of ovarian carcinoma with BZA (n=4 [0.1%]) than PBO (n=0); the difference was not statistically significant. Rates of breast-related and other gynecologic AEs were similar among groups.
  
  
  CONCLUSIONS
  BZA was associated with a favorable reproductive safety profile in postmenopausal women with osteoporosis over 7 years.
authors.affiliation: Palacios Institute of Women's Health, Calle Antonio Acuña, 9, 28009 Madrid, Spain. ipalacios@institutopalacios.com
authors.forename: Santiago
authors.initials: S
authors.lastname: Palacios
authors.forename: Tobie J
authors.initials: TJ
authors.lastname: de Villiers
authors.forename: Fiorenzo De Cicco
authors.initials: Fde C
authors.lastname: Nardone
authors.forename: Amy B
authors.initials: AB
authors.lastname: Levine
authors.forename: Robert
authors.initials: R
authors.lastname: Williams
authors.forename: Teresa
authors.initials: T
authors.lastname: Hines
authors.forename: Sebastian
authors.initials: S
authors.lastname: Mirkin
authors.forename: Arkadi A
authors.initials: AA
authors.lastname: Chines
mesh_terms: D000368:Aged; D050071:Bone Density Conservation Agents / Q000009:adverse effects* / Q000627:therapeutic use; D000077216:Carcinoma, Ovarian Epithelial; D004311:Double-Blind Method; D004714:Endometrial Hyperplasia / Q000453:epidemiology; D016889:Endometrial Neoplasms / Q000453:epidemiology; D004717:Endometrium / Q000000981:diagnostic imaging / Q000187:drug effects*; D005260:Female; D006801:Humans; D015994:Incidence; D007211:Indoles / Q000009:adverse effects* / Q000627:therapeutic use; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000139:chemically induced / Q000453:epidemiology; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy*; D010051:Ovarian Neoplasms / Q000139:chemically induced / Q000453:epidemiology; D017698:Postmenopause; D020845:Selective Estrogen Receptor Modulators / Q000009:adverse effects* / Q000627:therapeutic use; D016103:Spinal Fractures / Q000517:prevention & control; D014463:Ultrasonography; D014627:Vaginitis / Q000453:epidemiology
chemical_list: D050071:Bone Density Conservation Agents; D007211:Indoles; D020845:Selective Estrogen Receptor Modulators; C447119:bazedoxifene
keywords: AE; ANCOVA; ANOVA; BMD; BZA; Bazedoxifene; Breast; Clinical safety; ER; EU; Endometrium; European Union; Ovarian; PBO; SERM; Selective estrogen receptor modulator (SERM); TVU; adverse event; analysis of covariance; analysis of variance; bazedoxifene; bone mineral density; estrogen receptor; placebo; selective estrogen receptor modulator; transvaginal ultrasonography