Impact on uterine bleeding and endometrial thickness: tibolone compared with continuous combined estradiol and norethisterone acetate replacement therapy.
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.
Dören
M
M
Department of Obstetrics and Gynecology, Westfälische Wilhelms-Universität Münster, Germany.
Rübig
A
A
Coelingh Bennink
H J
HJ
Holzgreve
W
W
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
D045930:Anabolic Agents; D004338:Drug Combinations; D009652:Norpregnenes; D013607:Tablets; D004958:Estradiol; C032040:Trisequens; D004964:Estriol; C027385:tibolone; D009640:Norethindrone