vaginal atrophy associated with menopause. Clinical data on breast cancer are not available, but both in vitro and in vivo data suggest that ospemifene may have chemopreventive activity in breast tissue. Bazedoxifene is used as treatment for osteoporosis in postmenopausal women at increased risk of fracture. It has been shown to be relatively safe and well tolerated. It shows no breast or endometrial stimulation and in the first two years, the small increase is better in venous thromboembolism, and similar in the long term to other SERMs. The advantage of bazedoxifene over raloxifene is that it increases endothelial nitric oxide synthase activity and does not antagonize the effect of 17β-estradiol on vasomotor symptoms. The first tissue selective estrogen complex (TSEC) combines conjugated estrogens and the SERM bazedoxifene to blend their activities. The combination therapy is used in the treatment of moderate to severe vasomotor symptoms associated with menopause, prevention of postmenopausal osteoporosis as well as treatment of estrogen deficiency symptoms in non-hysterectomized postmenopausal women. The combination allows for the benefits of estrogen with regard to relief of vasomotor symptoms without estrogenic stimulation of the endometrium. Available forms Pharmacology Pharmacodynamics SERMs are competitive partial agonists of the ER. Different tissues have different degrees of sensitivity to the activity of endogenous estrogens, so SERMs produce estrogenic or antiestrogenic effects depending on the specific tissue in question as well as the percentage of intrinsic activity (IA) of the SERM. An example of a SERM with high IA and thus mostly estrogenic effects is chlorotrianisene, while an example of a SERM with low IA and thus mostly antiestrogenic effects is ethamoxytriphetol. SERMs like clomifene and tamoxifen are comparatively more in the middle in their IA and their balance of estrogenic and antiestrogenic activity. Raloxifene is a SERM that is more antiestrogenic than tamoxifen; both are estrogenic in bone, but raloxifene is antiestrogenic in the uterus while tamoxifen is estrogenic in this part of the body. Binding site SERM act on the estrogen receptor (ER), which is an intracellular, ligand-dependent transcriptional activator and belongs to the nuclear receptor family. Two different subtypes of ER have been identified, ERα and ERβ. ERα is considered the main medium where estrogen signals are transduced at the transcriptional level and is the predominant ER in the female reproductive tract and mammary glands while ERβ is primarily in vascular endothelial cells, bone, and male prostate tissue. ERα and ERβ concentration