Article

Shelly W, Draper MW, Krishnan V, Wong M, Jaffe RB. Selective estrogen receptor modulators: an update on recent clinical findings

Center for Reproductive Sciences, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, California, USA.
Obstetrical and Gynecological Survey (Impact Factor: 2.36). 04/2008; 63(3):163-81. DOI: 10.1097/OGX.0b013e31816400d7
Source: PubMed

ABSTRACT 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.

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    • "The current evidence indicates that each SERM has a unique array of clinical activities. The differences in the patterns of action of the SERMs suggest that each clinical end point must be evaluated individually , and the conclusions about any particular SERM can only be established through the appropriate clinical trials [12]. limitations of this study: The number of the study group was less. "
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    • "First, selective estrogen receptor modulators are compounds that act as agonists on one ER and antagonists at the other ER (Zandi et al., 2002). This strategy has attempted to enhance ERβ agonist activity while antagonizing ERα (Brinton, 2004; Shelly et al., 2008). The rationale for this approach is that chronic activation of ERα, which is highly expressed in breast, uterus and liver, may account for the now known side effects of chronic estrogen administration to post-menopausal women. "
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    • "Estrogen receptors are a target for therapeutic approaches to prevent cognition decline with aging or the development of affective and cognitive disorders after menopause. New selective modulators for estrogen receptors, such as arzoxifene, bazedoxifene, lasofoxifene, and ospemifene, among others, are being tested in clinical trials (Shelly et al., 2008). Before the therapeutic use of these drugs as neuroprotectants is considered, it is essential to learn much more about the expression and regulation of estrogen receptors and transcriptional cofactors in the aging brain and also about the impact of aging on the convergence of estrogen receptor signaling with other signaling pathways. "
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