Endometrial effects of tibolone

被引:65
作者
Archer, David F.
Hendrix, Susan
Gallagher, J. Chris
Rymer, Janice
Skouby, Sven
Ferenczy, Alex
den Hollander, Wil
Stathopoulos, Victoria
Helmond, Frans A.
机构
[1] Eastern Virginia Med Sch, CONRAD, Clin Res Ctr, Dept Obstet & Gynecol, Norfolk, VA 23507 USA
[2] Wayne State Univ, Hutzel Womens Hosp, Detroit, MI 48201 USA
[3] Creighton Univ, Med Ctr, Bone Metab Sect, Omaha, NE 68131 USA
[4] Kings Coll London, Sch Med, Guys & St Thomas Hosp, Dept Obstet & Gynaecol, London SE5 9RT, England
[5] Frederiksberg Univ Hosp, Dept Obstet & Gynecol, DK-2000 Copenhagen, Denmark
[6] Sir Mortimer B Davis Jewish Hosp, Montreal, PQ H3T 1E2, Canada
[7] McGill Univ, Montreal, PQ H3T 1E2, Canada
[8] NV Organon, NL-5340 BH Oss, Netherlands
[9] Organon Int, Roseland, NJ 07068 USA
关键词
D O I
10.1210/jc.2006-2207
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background and Objectives: The Tibolone Histology of the Endometrium and Breast Endpoints Study is a multicenter, randomized, double-blind study designed to address the conflicting reports in the literature about the endometrial safety of tibolone (1.25 or 2.5 mg/d). Tibolone was compared with continuous combined conjugated equine estrogen (CEE) plus medroxyprogesterone acetate (MPA) (0.625 + 2.5 mg/d). Methods: Subjects were randomized in a 1: 1: 2 ratio to tibolone 1.25 mg/d, 2.5 mg/d, and CEE/MPA, respectively. The one-sided 95% confidence interval (CI) has been evaluated for the incidence of abnormal endometrial histology (hyperplasia or carcinoma) and hyperplasia and carcinoma separately for each of the two treatment groups and the treatment groups combined after 1 and 2 yr of treatment with tibolone, compared with CEE/MPA. Results: A total of 3240 women were randomized, with 3224 receiving at least one dose of study medication. The incidence and upper one-sided 95% CI for the incidence of abnormal endometrium (hyperplasia or carcinoma), and hyperplasia and carcinoma separately, were calculated at end point, yr 1, and yr 2. The incidence (upper one-sided 95% CI) of abnormal endometrium at end point was 0.0 (0.5), 0.0 (0.4), and 0.2 (0.5) in the tibolone 1.25 mg, 2.5 mg, and CEE/MPA groups, respectively. During the entire treatment period, amenorrhea was reported more frequently with tibolone 1.25 mg (78.7%) and 2.5 mg (71.4%) than CEE/MPA (44.9%). Conclusion: The Tibolone Histology of the Endometrium and Breast Endpoints Study results confirm previous findings that tibolone does not induce endometrial hyperplasia or carcinoma in postmenopausal women, and it is associated with a better vaginal bleeding profile than CEE/MPA.
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页码:911 / 918
页数:8
相关论文
共 49 条
[1]   Effects of estrogen plus progestin on gynecologic cancers and associated diagnostic procedures - The Women's Health Initiative randomized trial [J].
Anderson, GL ;
Judd, HL ;
Kaunitz, AM ;
Barad, DH ;
Beresford, SAA ;
Pettinger, M ;
Liu, J ;
McNeeley, SG ;
Lopez, AM .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2003, 290 (13) :1739-1748
[2]  
[Anonymous], BLAUSTEINS PATHOLOGY
[3]  
[Anonymous], COCHRANE DATABASE SY
[4]  
ARCHER D, IN PRESS FERTIL STER
[5]   A randomized, open-label study of conjugated equine estrogens plus medroxyprogesterone acetate versus tibolone: effects on symptom control, bleeding pattern, lipid profile and tolerability [J].
Baracat, EC ;
Barbosa, IC ;
Giordano, MG ;
Haidar, MA ;
Marinho, RM ;
Menegocci, JC ;
Morais, KM ;
Tomaz, G ;
Wehba, S .
CLIMACTERIC, 2002, 5 (01) :60-69
[6]  
Beral V, 2005, LANCET, V365, P1543, DOI 10.1016/S0140-6736(05)66455-0
[7]   Vaginal ultrasound of the endometrium in postmenopausal women with symptoms of urogenital atrophy on low-dose estrogen or tibolone treatment: A comparison [J].
Botsis, D ;
Kassanos, D ;
Kalogirou, D ;
Antoniou, G ;
Vitoratos, N ;
Karakitsos, P .
MATURITAS, 1997, 26 (01) :57-62
[8]  
CHAPMAN MG, 2002, CLIMAETERIC S1, V5, P214
[9]   Influence of estrogen plus progestin on breast, cancer and mammography in healthy postmenopausal women - The Women's Health Initiative Randomized trial [J].
Chlebowski, RT ;
Hendrix, SL ;
Langer, RD ;
Stefanick, ML ;
Gass, M ;
Lane, D ;
Rodabough, RJ ;
Gilligan, MA ;
Cyr, MG ;
Thomson, CA ;
Khandekar, J ;
Petrovitch, H ;
McTiernan, A .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2003, 289 (24) :3243-3253
[10]   Comparative effects of tibolone and conjugated equine estrogens with and without medroxyprogesterone acetate on the reproductive tract of female cynomolgus monkeys [J].
Cline, JM ;
Register, TC ;
Clarkson, TB .
MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY, 2002, 9 (04) :242-252