The effects of tibolone in older postmenopausal women.
BACKGROUND
Tibolone has estrogenic, progestogenic, and androgenic effects. Although tibolone prevents bone loss, its effects on fractures, breast cancer, and cardiovascular disease are uncertain.


METHODS
In this randomized study, we assigned 4538 women, who were between the ages of 60 and 85 years and had a bone mineral density T score of -2.5 or less at the hip or spine or a T score of -2.0 or less and radiologic evidence of a vertebral fracture, to receive once-daily tibolone (at a dose of 1.25 mg) or placebo. Annual spine radiographs were used to assess for vertebral fracture. Rates of cardiovascular events and breast cancer were adjudicated by expert panels.


RESULTS
During a median of 34 months of treatment, the tibolone group, as compared with the placebo group, had a decreased risk of vertebral fracture, with 70 cases versus 126 cases per 1000 person-years (relative hazard, 0.55; 95% confidence interval [CI], 0.41 to 0.74; P<0.001), and a decreased risk of nonvertebral fracture, with 122 cases versus 166 cases per 1000 person-years (relative hazard, 0.74; 95% CI, 0.58 to 0.93; P=0.01). The tibolone group also had a decreased risk of invasive breast cancer (relative hazard, 0.32; 95% CI, 0.13 to 0.80; P=0.02) and colon cancer (relative hazard, 0.31; 95% CI, 0.10 to 0.96; P=0.04). However, the tibolone group had an increased risk of stroke (relative hazard, 2.19; 95% CI, 1.14 to 4.23; P=0.02), for which the study was stopped in February 2006 at the recommendation of the data and safety monitoring board. There were no significant differences in the risk of either coronary heart disease or venous thromboembolism between the two groups.


CONCLUSIONS
Tibolone reduced the risk of fracture and breast cancer and possibly colon cancer but increased the risk of stroke in older women with osteoporosis. (ClinicalTrials.gov number, NCT00519857.)
Cummings
Steven R
SR
San Francisco Coordinating Center and the California Pacific Medical Center Research Institute, San Francisco, USA.
Ettinger
Bruce
B
Delmas
Pierre D
PD
Kenemans
Peter
P
Stathopoulos
Victoria
V
Verweij
Pierre
P
Mol-Arts
Mirjam
M
Kloosterboer
Lenus
L
Mosca
Lori
L
Christiansen
Claus
C
Bilezikian
John
J
Kerzberg
Eduardo Mario
EM
Johnson
Susan
S
Zanchetta
Jose
J
Grobbee
Diederich E
DE
Seifert
Wilfried
W
Eastell
Richard
R
D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D015519:Bone Density / Q000187:drug effects; D001943:Breast Neoplasms / Q000517:prevention & control; D003110:Colonic Neoplasms / Q000517:prevention & control; D004311:Double-Blind Method; D016889:Endometrial Neoplasms / Q000139:chemically induced; D020847:Estrogen Receptor Modulators / Q000009:adverse effects / Q000627:therapeutic use*; D015914:Estrogen Replacement Therapy; D005260:Female; D006801:Humans; D008875:Middle Aged; D009652:Norpregnenes / Q000009:adverse effects / Q000627:therapeutic use*; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy* / Q000517:prevention & control; D017698:Postmenopause / Q000187:drug effects; D011859:Radiography; D012306:Risk; D016103:Spinal Fractures / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000517:prevention & control*; D020521:Stroke / Q000139:chemically induced
D000726:Androgen Antagonists; D020847:Estrogen Receptor Modulators; D009652:Norpregnenes; C027385:tibolone