The Effects of Tibolone in Older Postmenopausal Women

Abstract

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 wit h 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.)

Tamoxifen and risk of contralateral breast cancer among women with inherited mutations in BRCA1 and BRCA2: a meta-analysis

“…Clinical trials have demonstrated the efficacy of several medications to reduce the risk of breast cancer in women without preexisting cancer [20][21][22][23][24][25], but only tamoxifen citrate and raloxifene for 5 years are approved by the US Food and Drug Administration (FDA) for this purpose. It is also suggested that adjuvant tamoxifen for primary unilateral breast cancer treatment could reduce the risk of CBC in the general population [9].…”

The first multicenter and randomized clinical trial of herbal Fufang for treatment of postmenopausal osteoporosis

“…Eligible participants were required to have a natural menopausal history of 8-25 years and a BMD T-score of −2.0 or less at the lumbar spine using dual-energy X-ray absorptiometry (DXA). BMD T-score of −2.0 instead of −2.5 at the lumbar spine was selected based on consideration of overall clinical treatment efficacy in osteoporosis [4]. Exclusion criteria were: (1) previous exposure to toremifene, tamoxifen, droloxifene, lasofoxifene, or other investigational selective estrogen receptor modulators; (2) use of hormone replacement therapy within the past 3 months and use of the following medications within the previous 3 months: calcitonin or related products, raloxifene, sodium fluoride (at doses>2 mg/day), anabolic steroids, chronic oral glucocorticoid or related steroid, anticoagulant such as heparin (but excluding aspirin); (3) use of bisphosphonates during the past 24 months; (4) use of parathyroid hormone during the past 6 months; (5) use of any other investigational drugs during the past month; (6) radiographic evidence of more than three vertebral fractures; (7) current medical disease associated with the development of metabolic bone disease, including Paget disease, osteomalacia, bone marrow disease, hereditary disorders of calcium or mineral metabolism, adrenal disorders, poorly controlled diabetes mellitus (e.g., FBS>140 mg/dL), severe connective tissue disorders, gastrointestinal diseases, and obesity (BMI> 35 kg/m 2 ); (8) T-scores of the femoral neck or lumbar spine (L 1 -L 4 ) BMD more than 4.0 SD below the mean for young adults (T-score≤−4.0), lumbar spine ≤0.514 g/cm 2 (Hologic apparatus) or 0.654 g/cm 2 (GE Lunar apparatus), femoral neck ≤0.385 g/cm 2 (Hologic apparatus) or 0.400 g/cm 2 (GE Lunar apparatus); (9) current or past history of clinically significant hematological, endocrinological, cardiovascular, renal, hepatic, gastrointestinal, psychiatric, or neurological diseases or drug allergies to estrogen-like hormonal drugs; (10) screening laboratory abnormality exceeding the limits defined by the central laboratory; and (11) history of advanced scoliosis, osteoarthritis, or other clinical spinal deformity which would interfere with BMD measurement.…”

Breast cancer prevention with anti-estrogens: review of the current evidence and future directions

“…Bisphosphonates, Metformin, Aspirin, other nonsteroidal anti-inflammatory drugs and COX-2 inhibitors, synthetic steroid hormone Tibolone, Statins, Fenretinide (derivative of retinoic acid), Rexinoids have shown promise in cohort study or randomized study. Table 4 summarizes newer agents showing promise for breast cancer prevention [27][28][29][30][31][32][33][34][35][36]. However, the results are not conclusive and should be interpreted with caution.…”