Recent clinical data on selective estrogen receptor modulators (SERMs) have 
provided the basis for reassessment of the SERM concept. The molecular basis of 
SERM activity involves binding of the ligand SERM to the estrogen receptor (ER), 
causing conformational changes which facilitate interactions with coactivator or 
corepressor proteins, and subsequently initiate or suppress transcription of 
target genes. SERM activity is intrinsic to each ER ligand, which accomplishes 
its unique profile by specific interactions in the target cell, leading to 
tissue selective actions. We discuss the estrogenic and anti-estrogenic effects 
of early SERMs, such as clomiphene citrate, used for treatment of ovulation 
induction, and the triphenylethylene, tamoxifen, which has ER antagonist 
activity in the breast, and is used for prevention and treatment of ER-positive 
breast cancer. Since the development of tamoxifen, other triphenylethylene SERMs 
have been studied for breast cancer prevention, including droloxifene, 
idoxifene, toremifene, and ospemifene. Other SERMs have entered clinical 
development more recently, including benzothiophenes (raloxifene and 
arzoxifene), benzopyrans (ormeloxifene, levormeloxifene, and EM-800), 
lasofoxifene, pipendoxifene, bazedoxifene, HMR-3339, and fulvestrant, an 
anti-estrogen which is approved for breast cancer treatment. SERMs have effects 
on tissues containing ER, such as the breast, bone, uterine and genitourinary 
tissues, and brain, and on markers of cardiovascular risk. Current evidence 
indicates that each SERM has a unique array of clinical activities. Differences 
in the patterns of action of SERMs suggest that each clinical end point must be 
evaluated individually, and conclusions about any particular SERM can only be 
established through appropriate clinical trials.