title: Impact on uterine bleeding and endometrial thickness: tibolone compared with continuous combined estradiol and norethisterone acetate replacement therapy.
abstract: OBJECTIVE
  To evaluate endometrial thickness and the incidence of uterine bleeding in postmenopausal women using either tibolone 2.5 mg or continuous combined 2 mg estradiol and 1 mg norethisterone acetate (E+NETA) daily as hormone replacement therapy.
  
  
  METHODS
  We compared diary records of self-reported uterine bleeding and measurements of endometrial thickness, area, and volume by transvaginal sonography at baseline and after 1, 3, 6, and 12 months in a 1-year, prospective, randomized, double-blind, single-center trial of 100 postmenopausal women aged 46-69 years. Bleeding frequencies and endometrial thickness were assessed by Chi-square tests and analysis of covariance, respectively.
  
  
  RESULTS
  Self-reported bleeding was significantly less in the tibolone group. Bleeding episodes were reported by 27.7% of women in the tibolone group and by 59.2% in the E+NETA group. The mean number of days with bleeding was 5.8 +/- 27.0 in the tibolone group and 35.6 +/- 58.6 in the E+NETA group. Six women in the tibolone group and seven in the E+NETA group discontinued the study; three in the E+NETA group because of bleeding. The mean endometrial thickness at baseline was 2.56 +/- 0.81 mm in the tibolone group and 2.58 +/- 1.04 mm in the E+NETA group. After 1 year, the corresponding figures were 3.32 +/- 1.58 mm and 3.07 +/- 1.68 mm. Thus, 86% of women in the tibolone group and 93% in the E+NETA group had an endometrial thickness of less than 5 mm.
  
  
  CONCLUSIONS
  Use of tibolone 2.5 mg daily for 1 year was associated with significantly less bleeding and spotting compared with daily continuous combined 2 mg estradiol and 1 mg norethisterone acetate in postmenopausal women in the presence of both minimal and nonprogressive increase of endometrial thickness associated with the two regimens.
authors.affiliation: Department of Obstetrics and Gynecology, Westfälische Wilhelms-Universität Münster, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Dören
authors.forename: A
authors.initials: A
authors.lastname: Rübig
authors.forename: H J
authors.initials: HJ
authors.lastname: Coelingh Bennink
authors.forename: W
authors.initials: W
authors.lastname: Holzgreve
mesh_terms: D000368:Aged; D045930:Anabolic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D004311:Double-Blind Method; D004338:Drug Combinations; D004714:Endometrial Hyperplasia / Q000139:chemically induced* / Q000000981:diagnostic imaging / Q000453:epidemiology; D019160:Endosonography; D004958:Estradiol / Q000008:administration & dosage / Q000009:adverse effects*; D004964:Estriol / Q000008:administration & dosage / Q000009:adverse effects*; D015914:Estrogen Replacement Therapy / Q000009:adverse effects* / Q000706:statistics & numerical data; D005260:Female; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D009640:Norethindrone / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D009652:Norpregnenes / Q000008:administration & dosage / Q000009:adverse effects*; D011446:Prospective Studies; D013607:Tablets; D014592:Uterine Hemorrhage / Q000139:chemically induced* / Q000000981:diagnostic imaging / Q000453:epidemiology; D014621:Vagina
chemical_list: D045930:Anabolic Agents; D004338:Drug Combinations; D009652:Norpregnenes; D013607:Tablets; D004958:Estradiol; C032040:Trisequens; D004964:Estriol; C027385:tibolone; D009640:Norethindrone