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. 2016 Oct 12;2016(10):CD008536. doi: 10.1002/14651858.CD008536.pub3

Summary of findings 4. Tibolone compared with combined HT for postmenopausal women: adverse events.

Tibolone compared with combined HT for postmenopausal women: adverse events
Population: postmenopausal women with or without vasomotor symptoms
 Settings: outpatient or community
 Intervention: tibolone
 Comparison: combined HT
Outcomes Illustrative comparative risks* (95% CI) Relative effect
 (95% CI) Number of participants
 (studies) Quality of the evidence
 (GRADE) Comments
Assumed risk Corresponding risk
Combined HT Tibolone
Unscheduled bleeding (all doses) 
 Follow‐up: 3 to 36 months (median 12) 474 per 1000 224 per 1000 
 (178 to 270) OR 0.32 
 (0.24 to 0.41) 6438
 (16 studies) ⊕⊕⊝⊝
 moderatea  
Endometrial cancer (all doses) 
 Follow‐up: 6.8 to 36 months (median 12) See comments OR 1.47 
 (0.23 to 9.33) 3689
 (5 studies) ⊕⊝⊝⊝
 very lowb,c Events very rare in both groups. Total of 3 events: 2/1826 in tibolone group, 1/1863 in combined HT group
Breast cancer; women without previous breast cancer (all doses) 
 Follow‐up: 6.8 to 36 months (median 24) 3 per 1000 6 per 1000
(3 to 13)
OR 1.69 
 (0.78 to 3.67) 4835
 (5 studies) ⊕⊝⊝⊝
 very lowb,c  
Venous thromboembolic events (clinical evaluation; all doses) 
 Follow‐up: 6.8 to 24 months (median 12) 3 per 1000 1 per 1000
(0 to 6)
OR 0.44 
 (0.09 to 2.14) 4529
 (4 studies) ⊕⊝⊝⊝
 very lowb,c  
Cardiovascular events (all doses) 
 Follow‐up: 2 to 3 years 17 per 1000 10 per 1000
(4 to 27)
OR 0.63 
 (0.24 to 1.66) 3794
 (2 studies) ⊕⊝⊝⊝
 very lowb,c  
Cerebrovascular event (all doses) 
 Follow‐up: 3.4 to 24 (median 9.4) months 1 per 1000 1 per 1000
(0 to 3)
OR 0.76 
 (0.16 to 3.66) 4562
 (4 studies) ⊕⊝⊝⊝
 very lowb,c  
Mortality from any cause (tibolone 2.5 mg/d) 
 Follow‐up: 3.4 to 24 (median 9.4) months See comments OR 3.05 
 (0.12 to 75.2) 970
 (2 studies) ⊕⊝⊝⊝
 very lowb,c Only 1 event (in tibolone group): 1/485 vs 0/485
*The basis for the assumed risk is the median control group risk across studies. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI)
 CI: confidence interval; OR: odds ratio
GRADE Working Group grades of evidence
 High quality: Further research is very unlikely to change our confidence in the estimate of effect
 Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate
 Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate
 Very low quality: We are very uncertain about the estimate

aDowngraded one level for serious risk of bias: poor reporting of study methods and potential conflict of interest in some studies

bDowngraded two levels for very serious risk of bias: poor reporting of study methods and potential conflict of interest in some studies

cDowngraded one level for serious imprecision: low event rate. Findings compatible with meaningful benefit in one or both arms, or with no effect