The Tissue-Selective Estrogen Complex: A Review of Current Evidence

The tissue-selective estrogen complex (TSEC) has recently entered the market for the treatment of postmenopausal osteoporosis, and is particularly targeted to women with significant vasomotor symptoms. This review appraises the evidence behind the only approved TSEC to-date, a combination of bazedoxifene and conjugated estrogens, with regards to its efficacy and relevant safety concerns. The majority of evidence that has led to its approval is derived from the SMART study. This large phase III trial with several substudies was aimed at discerning the effects of the TSEC on various estrogen-responsive tissues in comparison to raloxifene and placebo. Overall, the evidence thus far suggests a superior improvement in lumbar bone mineral density of 1.01% ± 0.28% as well as decrease in the frequency of hot flushes. Regarding safety concerns, endometrial thickness did not change over the treatment course, and investigators also identified a modest reduction in breast density. While there was no difference in rates of venous thromboembolism between treatment and placebo groups in a 2-year follow-up period, the effects of the drug on coagulation profiles are similar to those seen with hormone replacement therapy. Thus, the drug's effects on venous thromboembolism risk over a longer treatment course remain unclear. In conclusion, the actual efficacy of the TSEC for postmenopausal osteoporosis remains as yet undefined, given the lack of fracture prevention data. The evidence thus far does seem to suggest a beneficial effect on vasomotor symptoms and a generally favorable side effect profile. However, it should be noted that only one study has addressed this question thus far, and so the repeatability of the findings is still in question.