Tibolone, selective estrogen receptor modulators (SERMs) like tamoxifen and 
raloxifene, and estrogen (+/-progestogen) treatments prevent bone loss in 
postmenopausal women. They exert their effects on bone via the estrogen receptor 
(ER) and the increase in bone mass is due to resorption inhibition. The effect 
of SERMs on bone mineral density is less than that with the other treatments, 
but the SERM raloxifene still has a positive effect on vertebral fractures. In 
contrast to tibolone and estrogens (+/-progestogen), SERMs do not treat 
climacteric complaints, whilst estrogen plus progestogen treatments cause a high 
incidence of bleeding. Estrogen plus progestogen combinations have compromising 
effects on the breast. Tibolone and SERMs do not stimulate the breast or 
endometrium. Unlike SERMs, tibolone does not possess antagonistic biological 
effects via the ER in these tissues. Estrogenic stimulation in these tissues is 
prevented by local metabolism and inhibition of steroid metabolizing enzymes by 
tibolone and its metabolites. SERMs and estrogen (+/-progestogen) treatments 
increase the risk of venous thromboembolism (VTE), whilst estrogen 
(+/-progestogen) combinations have unwanted effects on cardiovascular events. So 
far, no detrimental effects of tibolone have been observed with respect to VTE 
or cardiovascular events. The clinical profile of tibolone therefore has 
advantages over those of other treatment modalities. It is also clear that 
tibolone is a unique compound with a specific mode of action and that it belongs 
to a separate class of compounds that can best be described as selective, tissue 
estrogenic activity regulators (STEARs).