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PubMed2002

ACOG practice bulletin. Selective estrogen receptor modulators. Number 39, October 2002 (replaces Committee Opinion Number 224, October 1999).

Selective estrogen receptor modulators (SERMs) are synthetic compounds that bind estrogen receptors and produce agonistic activity in some tissues while acting as estrogen antagonists in other tissues. Although referred to collectively, their effects in different organs (eg, endometrium, urinary tract) are far from uniform. Much confusion exists about the indications for their use and the effects of these compounds. The purpose of this document is to review the use of SERMs for breast cancer risk reduction and skeletal protection as approved by the U.S. Food and Drug Administration (FDA).

Adult↗
PubMed2002

Prevention and treatment of experimental breast cancer with the combination of a new selective estrogen receptor modulator, arzoxifene, and a new rexinoid, LG 100268.

The selective estrogen receptor modulator arzoxifene and the rexinoid LG 100268 were active not only as single agents for prevention and treatment of breast cancer in the rat model that uses nitrosomethylurea as the carcinogen but also showed striking synergy, both preventively and therapeutically, in a series of six experiments with a total of 465 rats. Mechanistic studies in cell culture reported here suggest that enhancement of stromal-epithelial interactions may contribute to this synergy. The possible clinical use of the combination of arzoxifene and LG 100268 for prevention of breast cancer in women at high risk, for treatment of women in the adjuvant setting, or for treatment of end-stage disease should now be considered.

Animals↗
PubMed2001

Selective estrogen receptor modulators: mechanism of action and clinical experience. Focus on raloxifene.

Selective estrogen receptor modulators (SERMs) are a diverse group of compounds that bind with specific, high-affinity binding to the estrogen receptor (ER). Depending on the tissue, SERMs can act as either ER agonists or antagonists. Recent advances in ER biology have provided insight into possible mechanisms by which SERMs elicit these tissue-specific estrogen agonist and estrogen antagonist activities. The estrogen response pathway has been shown to differ among target tissues depending on various tissue and cellular factors, such as the ER subtype, the structure of the bound receptor-ligand complex, and the tissue-specific cellular transcriptional machinery. Clinically available SERMs include clomiphene, tamoxifen and toremifene, which are triphenylethylenes, and raloxifene, a benzothiophene. Raloxifene has estrogen agonist effects on bone, serum lipids, and arterial vasculature, and estrogen antagonist effects in breast and uterus. Clinical trial data for raloxifene is used to illustrate some of the mechanisms by which SERMs exert their tissue-specific estrogen agonist and estrogen antagonist effects. The complex pharmacology surrounding the tissue selectivity of SERMs is discussed.

Clinical Trials as Topic↗
PubMed2002

Recovery of proximal tibia bone mineral density and strength, but not cancellous bone architecture, after long-term bisphosphonate or selective estrogen receptor modulator therapy in aged rats.

Various bisphosphonates and the selective estrogen receptor modulator (SERM) raloxifene are approved treatments of postmenopausal osteoporosis. They increase bone mineral density (BMD), decrease bone turnover, and reduce vertebral fracture incidence through different cellular mechanisms. We investigated the bone cellular activities, architecture, mineral content/density, and strength of ovariectomized (ovx) rats on a long-term bisphosphonate or SERM treatment, at doses of either agent correcting bone strength. Eleven weeks postovariectomy, 6-month-old rats were treated with the SERM MDL 103,323 or with the bisphosphonate pamidronate for 5 months. Doses of pamidronate and MDL 103,323 were selected from previous studies showing correction of the ovx-induced decrease of ultimate strength of proximal tibia. Ultimate and yield strengths, BMD, and histomorphometric parameters were all quantified at the same site, i.e., the proximal tibia metaphysis. Long-term pamidronate decreases bone turnover and bone formation activity, leading to trabecular thinning. MDL 103,323 decreases bone turnover to a lesser extent, and slightly protects trabecular architecture by uncoupling bone resorption and formation activities. The yield strength is corrected by pamidronate, but not by MDL 103,323 treatment. However, neither compound restores the ovariectomy-induced cancellous bone loss. Total tissue area and cortical thickness are unchanged with pamidronate or MDL 103,323 treatment, indicating that cortical bone mass, thickness, and cross-sectional area are not modified. The discrepancy between proximal tibia BMD and mechanical resistance to fracture modifications, on the one hand, and cancellous bone volume, on the other hand, could be due to changes in the degree of mineralization of bone matrix and/or of the intrinsic properties of the bone matrix.

Aging↗
PubMedDate not supplied

Proliferative lesions of ovarian granulosa cells and reversible hormonal changes induced in rats by a selective estrogen receptor modulator.

This study assessed the effects of raloxifene, a selective estrogen receptor modulator (SERM), on ovarian morphology and circulating hormone levels in rats. Female Fischer-344 rats (65/group) were given dietary raloxifene for 6 months at average daily doses of 0, 15, 75, and 365 mg/kg. Morphologic evaluation of ovaries was conducted on 25 rats/group at the end of the treatment period and from 20 rats per group after 1 and 3 months withdrawal from treatment. Plasma hormone analyses were conducted on 10 rats pergroup at the end of the treatment period and aftereach withdrawal period. Treatment with raloxifene for 6 months resulted in disruption of the hypothalamic-pituitary-ovarian axis, manifested by increased plasma concentrations of luteinizing hormone (LH) and estradiol-17beta (E2), and failure of ovulation, manifested by ovarian follicular prominence (retained anovulatory follicles), lack of corpora lutea (CL), and depressed plasma progesterone (P4). Many (56% to 80%) rats in all raloxifene treated groups had focal, minimal to slight hyperplasia of granulosa cells within individual retained follicles. A few treated rats in the mid- and high-dose groups (2 of 25 and 3 of 25, respectively) had more extensive focal proliferation of granulosa cells. These foci were approximately 3 to 6 mm in overall size and were characterized by moderate papillary proliferation of large granulosa cells associated with cystic spaces, often with hemorrhage. In 4 of the 5 rats with this focal cystic granulosa cell hyperplasia, the remainder of the involved ovary and the contralateral ovary were atrophic. After 1 or 3 months of drug withdrawal, most previously treated rats examined had morphologic evidence of ovarian cyclic changes. including developing follicles, various stages of CL, and normal plasma levels of LH, E2, and P4. Continued lack of cyclic changes was limited to 4 of 20 rats from the low-dose group after 1 month of recovery and to 1 low dose rat after 3 months. Intrafollicular granulosa cell hyperplasia was not seen in rats in the reversibility phase. Areas of prior focal cystic granulosa cell hyperplasia were represented by focal sclerosis that included hemorrhage and/or hemosiderin. The foci of sclerosis were associated with cystic spaces after 1 month and were solid after 3 months. A granulosa cell tumor, approximately 12-13 mm diameter, was present in a high-dose rat in the 3-month reversibility group. This tumor effaced 1 ovary and was characterized by proliferative granulosa cells, usually in papillary formations and cords within cystic spaces. This rat had atrophy of the uninvolved ovary, excessive plasma levels of E2 and prolactin, and high P4 levels considering the absence of CL. The results of this study indicate that ovarian granulosa cells in rats are susceptible to proliferative changes when stimulated chronically with excessive trophic hormones. Most of these proliferative changes were reversible upon cessation of the hormonal stimulation. However, the proliferative lesion in one treated rat progressed to apparent autonomous (neoplastic) growth.

Animals↗
PubMedDate not supplied

Proliferative lesions of ovarian granulosa cells and reversible hormonal changes induced in rats by a selective estrogen receptor modulator.

This study assessed the effects of raloxifene. a selective estrogen receptor modulator (SERM), on ovarian morphology and circulating hormone levels in rats. Female Fischer-344 rats (65/group) were given dietary raloxifene for 6 months at average daily doses of 0, 15, 75, and 365 mg/kg. Morphologic evaluation of ovaries was conducted on 25 rats/group at the end of the treatment period and from 20 rats per group after 1 and 3 months withdrawal from treatment. Plasma hormone analyses were conducted on 10 rats per group at the end of the treatment period and after each withdrawal period. Treatment with raloxifene for 6 months resulted in disruption of the hypothalamic-pituitary-ovarian axis, manifested by increased plasma concentrations of luteinizing hormone (LH) and estradiol-17beta (E2), and failure of ovulation, manifested by ovarian follicular prominence (retained anovulatory follicles), lack of corpora lutea (CL), and depressed plasma progesterone (P4). Many (56% to 80%) rats in all raloxifene treated groups had focal, minimal to slight hyperplasia of granulosa cells within individual retained follicles. A few treated rats in the mid- and high-dose groups (2 of 25 and 3 of 25, respectively) had more extensive focal proliferation of granulosa cells. These foci were approximately 3 to 6 mm in overall size and were characterized by moderate papillary proliferation of large granulosa cells associated with cystic spaces, often with hemorrhage. In 4 of the 5 rats with this focal cystic granulosa cell hyperplasia, the remainder of the involved ovary and the contralateral ovary were atrophic. After 1 or 3 months of drug withdrawal, most previously treated rats examined had morphologic evidence of ovarian cyclic changes, including developing follicles, various stages of CL, and normal plasma levels of LH, E2, and P4. Continued lack of cyclic changes was limited to 4 of 20 rats from the low-dose group after 1 month of recovery and to 1 low dose rat after 3 months. Intrafollicular granulosa cell hyperplasia was not seen in rats in the reversibility phase. Areas of prior focal cystic granulosa cell hyperplasia were represented by focal sclerosis that included hemorrhage and/or hemosiderin. The foci of sclerosis were associated with cystic spaces after 1 month and were solid after 3 months. A granulosa cell tumor, approximately 12-13 mm diameter, was present in a high-dose rat in the 3-month reversibility group. This tumor effaced 1 ovary and was characterized by proliferative granulosa cells, usually in papillary formations and cords within cystic spaces. This rat had atrophy of the uninvolved ovary, excessive plasma levels of E2 and prolactin, and high P4 levels considering the absence of CL. The results of this study indicate that ovarian granulosa cells in rats are susceptible to proliferative changes when stimulated chronically with excessive trophic hormones. Most of these proliferative changes were reversible upon cessation of the hormonal stimulation. However, the proliferative lesion in one treated rat progressed to apparent autonomous (neoplastic) growth.

Animals↗
PubMed2001

Selective estrogen receptor modulator effects on serum lipoproteins and vascular function in postmenopausal women and in hypercholesterolemic men.

Epidemiological observations, clinical mechanistic studies, and basic laboratory research suggest that estrogen therapy is associated with beneficial cardiovascular effects in postmenopausal women. Estrogen has a multitude of biological effects that may account for this apparent benefit (which remains to be proved in randomized clinical trials), including favorable effects on the lipid profile, increased endothelial nitric oxide bioactivity, and enhanced fibrinolysis. However, long-term estrogen therapy increases the risk of breast and endometrial cancers. Raloxifene, a benzothiophene derivative that binds to the estrogen receptor, is a selective estrogen receptor modulator, producing estrogen-agonist effects in some tissues (liver, bone) and estrogen-antagonistic effects in others (breast, uterus), and may prove to be an option for women with atherosclerosis or its risk factors. This review updates the current knowledge of the biological effects of selective estrogen receptor modulators of potential cardiovascular importance in postmenopausal women.

Animals↗
PubMed2005

Synthesis and structure-activity relationships of analogs of EM-652 (acolbifene), a pure selective estrogen receptor modulator. Study of nitrogen substitution.

EM-652 (acolbifene) analogs have been synthesized as selective estrogen receptor modulators. Substitution on the nitrogen atom of these 2H-1-benzopyran derivatives has been studied for its influence on antiestrogenic activity. Binding to the rat estrogen receptor, inhibition of estradiol-stimulated proliferation of T-47D breast cancer cells, as well as antiuterotrophic and uterotrophic activities in ovariectomized mice have been evaluated. 2H-1-Benzopyran 1b (EM-343, racemic form of EM-652), which contains a piperidine ring, shows the best pharmacological profile; RBA = 380, IC50 value = 0.110 nM (in T-47D cells), as well as 63% and 84% antiuterotrophic inhibitions at the 7.5 and 75 nmol doses, respectively.

Animals↗
PubMed1998

Therapeutic potential of selective estrogen receptor modulators.

The hormone estradiol has effects on many tissues in both males and females. Some of these effects, such as inhibition of cancer growth and modulation of the devastating effects of aging on bone, brain, skin and bladder, are good. Others, such as the effect on the breast and endometrium, are undesirable. The task of designing drugs that would have only the good effects of estradiol has, until recently, seemed almost impossible because it was thought that there was only one estrogen receptor and that an estrogenic agent was definitively categorized as an estrogen agonist or an antagonist. More recently we have learnt that there are two estrogen receptors which, under certain conditions, have opposite effects on gene transcription. In addition, it is now understood that agents cannot be described as agonists or antagonists because a single agent can be an agonist in one tissue and an antagonist in another. The term 'selective' estrogen receptor modulator' was designed to incorporate this. The idea of estrogen receptor modulators has raised new hope that tissue specific estrogens or anti-estrogens can be designed.

Animals↗
PubMed2006

Selective estrogen receptor modulators: A possible new treatment of osteoporosis in males.

More recently, osteoporosis in men has been recognized as an important public health problem. Bone loss begins in mid life and is associated with the decline of the sex steroids production. Although there is no equivalent of the menopause, gonadal function in men is affected in a slow progressive way leading to hypogonadism. Testosterone, the major androgen in men, exerts its effect on bone by local conversion to 5alpha-dihydrotestosterone or by aromatization to estrogens. Several studies have found that estrogen, rather than testosterone, levels are more closely correlated with BMD in elderly men. Selective estrogen receptor modulator (SERM) raloxifene binds to estrogen receptors and exhibit estrogenic effect in bone, but, contrary to estrogen, without feminizing effect. There are limited numbers of studies investigating the effects of SERMs in males. Animal studies demonstrated that SERMs inhibit bone turnover and prevent bone loss in orchidectomised adult male rats. Raloxifene has been shown to increase bone mineral density of the hip in men receiving androgen deprivation therapy for prostate cancer. Moreover, experimental data demonstrated dramatic increase in cell death in human prostate cancer cell lines after the treatment with raloxifene. All these observations suggest that SERMs may be useful for the prevention and treatment of osteoporosis not only in postmenopausal women but also in elderly men. However, our hypothesis should be tested in a proper designed clinical trial. Several important issues have to be addressed. Does the same drug dose that has been shown to be effective in postmenopausal women should be used in men, too? Does treatment with SERMs reduce the fracture risk in men and is it comparable to that observed in women? Does treatment with SERMs have any beneficial effect on cardiovascular system and prostate cancer? And finally, do men experience adverse events other than women treated with SERMs? Answering to these questions will have great impact in getting the decision of possible SERMs usage in the treatment of osteoporosis in elderly males.

Aged↗
PubMed2005

Selective reduction of estrogen receptor (ER) positive breast cancer occurrence by estrogen receptor modulators supports etiological distinction between ER positive and ER negative breast cancers.

Reports that selective estrogen receptor modulators (SERMs) reduce occurrence of only estrogen receptor (ER) positive tumors strongly support the etiological distinction between ER positive and ER negative breast cancers. Based on these evidences three concepts are described: Concept I. The occurrence of ER negative tumor cells might be a consequence of the clonal selection among tumor cells. This would lead to mosaicism in the ER expression. If ER negative cells become the most prevalent clone, the patient will be diagnosed to have an ER negative breast cancer. Since all cancers start as ER positive, SERMs should equally prevent occurrence of ER positive and ER negative breast cancers, but this prediction is evidently wrong. Concept II. Mammary ducts normally contain ER positive and ER negative cells, both prone to malignancy. Cancer occurrence in ductal cells that normally lack ER would be unrelated to estrogen exposure or SERMs protection. Estrogen and SERMs can influence cancer occurrence only in ER positive ductal cells. The main drawback is that this concept does not predict occurrence of mosaicism in ER expression among tumor cells. Unified Concept I and II. To overcome limitations of described concept a unified concept is presented. Cancers from ER positive ductal cells start as pure ER positive tumors and those from ER negative ductal cells as pure ER negative tumors. During the preclinical phase, in some ER positive tumors, clonal selection introduces ER negative clones. These tumors become mosaic in the cellular ER expression, some of them predominantly ER positive other ER negative. Estrogen deprivation, or SERMs can help mostly to patients with pure ER positive, or mosaic ER positive tumors. Since the dominant metastatic clone can have different ER status from the primary breast tumor, both surprising successes and failures of endocrine therapy can be expected in tumors with mosaic ER expression.

Breast Neoplasms↗
PubMedDate not supplied

Hormone therapy and selective estrogen receptor modulators for prevention of coronary heart disease in postmenopausal women estrogen replacement from the cardiologist's perspective.

Coronary heart disease is the leading cause of morbidity and mortality in women older than the age of 50 in the United States today. Traditional cardiovascular risk factors (hyperlipidemia, glucose intolerance, and hypertension) are more clearly associated with significant cardiovascular risk after menopause. The increased incidence of cardiovascular events in postmenopausal women and the evidence that cardiovascular disease on average manifests a decade later in women compared with men suggests that estrogen deficiency may predispose women to a higher cardiovascular risk. Numerous biologic mechanisms have been proposed that relate use of hormone therapy (HT) to improved lipid profiles, insulin sensitivity, and vascular reactivity. Early observational trials in the last 2 decades showed a significant decrease in cardiovascular events. Recently published randomized clinical trial results, however, have led to uncertainty about the earlier established cardiovascular benefits of HT. To complicate issues further, alternative estrogenlike compounds, selective estrogen receptor modulators, are being introduced that appear to convey similar cardiovascular benefit and notably less cancer risk than HT. The newly released randomized trials on hormone and nonhormonal agents are reviewed.

Coronary Disease↗
PubMed1998

Synthesis and pharmacology of conformationally restricted raloxifene analogues: highly potent selective estrogen receptor modulators.

The 2-arylbenzothiophene raloxifene, 1, is a selective estrogen receptor modulator (SERM) which is currently under clinical evaluation for the prevention and treatment of postmenopausal osteoporosis. In vivo structure-activity relationships and molecular modeling studies have indicated that the orientation of the basic amine-containing side chain of 1, relative to the stilbene plane, is an important discriminating factor for the maintenance of tissue selectivity. We have constructed a series of analogues of 1 in which this side chain is held in an orientation which is orthogonal to the stilbene plane, similar to the low-energy conformation predicted for raloxifene. Herein, we report on the synthesis of these compounds and on their activity in a series of in vitro and in vivo biological assays reflective of the SERM profile. In particular, we describe their ability to (1) bind the estrogen receptor, (2) antagonize estrogen-stimulated proliferation of MCF-7 cells in vitro, (3) stimulate TGF-beta3 gene expression in cell culture, (4) inhibit the uterine effects of ethynyl estradiol in immature rats, and (5) potently reduce serum cholesterol and protect against osteopenia in ovariectomized (OVX) rats without estrogen-like stimulation of uterine tissue. These data demonstrate that one of these compounds, LY357489,4, is among the most potent SERMs described to date with in vivo efficacy on bone and cholesterol metabolism in OVX rats at doses as low as 0.01 mg/kg/d.

Animals↗
PubMed2003

Acute vascular effects of the selective estrogen receptor modulator EM-652 (SCH 57068) in the rat mesenteric vascular bed.

OBJECTIVE: Selective estrogen receptor modulators (SERMs) represent a class of compounds that act as either estrogen receptor agonist or antagonist in a tissue-selective manner. SERMs exert beneficial effects on bone and lipids but are not associated with an increased risk of breast or uterine carcinoma. 17beta-estradiol (E2) and SERMs such as raloxifene and tamoxifen acutely relax coronary arteries. EM-652 (SCH 57068) is a 4th generation SERM acting as pure antiestrogen in the mammary gland and endometrium. The effects of SERMs on the mesenteric vasculature are unknown. In the present study, the vascular effects of EM-652 and E2 on the rat mesentery were investigated. METHODS: Isolated perfused (5 ml/min) mesenteric vascular bed (MVB) was preconstricted with methoxamine. Increasing doses (0.1-10 microM) of EM-652 or E2 were infused into the perfusate. RESULTS: EM-652 and E2 relaxed MVBs removed from intact and gonadectomized female and male rats. The amplitude of EM-652 responses was consistently greater than those of E2 and its potency was similar or greater than that of other SERMs. EM-652 and E2 relaxed MVB by an endothelium-independent mechanism. The estrogen receptor (ER) antagonist ICI 182,780 attenuated E2-induced relaxations but only partially block the effects of EM-652. Inhibition of the nitric oxide synthase/cGMP pathway with N(G)-nitro-arginine-methyl-ester (L-NAME) and 1H-(1,2,4)oxadiazolo(4,3-a)quinoxaline-1-one (ODQ) or of prostanoid synthesis with indomethacin failed to reduce EM-652 responses. The vascular effects of EM-652 were also unaffected by potassium channels blockers or inhibitors/scavengers of reactive oxygen species. EM-652 attenuated the vasoconstrictor responses induced by adrenergic agonists and endothelin-1. CONCLUSIONS: EM-652 acutely relaxes the mesenteric vasculature by an endothelium-independent pathway which is partly mediated by ER, providing a novel mechanism by which this SERM may exert beneficial actions on the vascular system.

Animals↗
PubMed2001

Comparative tolerability of first-generation selective estrogen receptor modulators in breast cancer treatment and prevention.

In general, the selective estrogen receptor modulators (SERMs) currently indicated for the treatment and prevention of breast cancer, i.e. tamoxifen and toremifene, are fairly well tolerated. However, tamoxifen has been shown to induce hepatocellular carcinomas in rats, but not in humans, and can increase the risk of endometrial cancer in humans by two to three times. Other potentially serious adverse effects which have been associated with tamoxifen and toremifene therapy include vasomotor symptoms, an increased risk of venous thromboembolic events, and an increased incidence of cataracts and ocular toxicity, fatty liver, and nonmalignant hepatic and uterine changes. In addition, long term tamoxifen use almost always results in resistance to the drug and, indeed, has actually been shown to promote tumour proliferation in human breast cancer cells. Both tamoxifen and toremifene display drug interactions with a variety of drug classes. The adverse events associated with these compounds have raised significant concerns regarding their widespread use for the treatment and prevention of breast cancer. In addition, because of the weakness and scarcity of the data on toremifene, any conclusions about its tolerability remain tentative until outcomes of ongoing clinical trials in the adjuvant setting are known. A third SERM, raloxifene, is the focus of several large randomised trials examining its efficacy in the prevention of breast cancer. At present, each potential adverse event needs to be weighed against potential benefits in the decision to undergo SERM treatment. An array of therapies is currently available for patients with breast cancer and women at increased risk of disease; the risk-to-benefit ratio for each agent should be carefully examined in determining the most advantageous regimen.

Animals↗
PubMed2003

Long-term toxicities of selective estrogen-receptor modulators and antiaromatase agents.

Published literature indicates that the selective estrogen-receptor modulators (SERMs) tamoxifen and raloxifene (Evista) have favorable effects on bone density, lipid profiles, and the incidence of second breast cancers, and unfavorable effects on the incidence of venous thrombosis and hot flushes. Tamoxifen increases the risk of endometrial cancer, but raloxifene does not. The effects of SERMs on sexual function and cognition are unclear. Because the selective antiaromatase agents are relatively new, the long-term effects of these agents on normal tissues are less well established. It appears that the nonsteroidal agents (anastrozole [Arimidex], letrozole [Femara]) and steroidal (exemestane [Aromasin]) antiaromatase agents may have different effects on normal tissues. Preliminary data demonstrate that anastrozole increases the risk of arthralgias and produces a decrease in bone density. In contrast, exemestane appears to favorably affect bone density and lipid profile, similar to tamoxifen and raloxifene. The incidence of contralateral breast cancer is decreased in women on adjuvant anastrozole, but data for the other antiaromatase agents are not yet available. Hot flushes have been reported with the use of selective aromatase inhibitors, but their incidence seems to be comparable to what is reported with SERMs. Antiaromatase agents do not appear to cause venous thrombosis. More information about the effects of the antiaromatase agents on normal tissue will become available as data from ongoing adjuvant and chemoprevention trials are reported. Clinically, we should be conscious of the differences between antiaromatase agents and SERMs and their impact on women's health.

Adult↗
PubMed1999

Selective estrogen receptor modulators: Women's panacea for the next millennium?

The purpose of this review is to assimilate relevant experimental and clinical information available on selective estrogen receptor modulators with respect to their potential use as agents to improve women's health in the postmenopausal years. In addition, the mechanisms of action of these drugs are outlined. Selective estrogen receptor modulators represent an exciting group of antiestrogens that possess agonist action on bone, lipids, and lipoproteins and antagonistic action in the endometrium and breast. Thus in theory these drugs may preserve bone density and reduce the risk of osteoporotic fracture and coronary heart disease at the same time that they lower the incidences of breast and endometrial neoplasms. Short-term data with the use of raloxifene suggest that bone is preserved and lipid profiles are less atherogenic. Long-term studies are needed to determine whether raloxifene or other selective estrogen receptor modulators are associated with any decrease in the risk of breast or endometrial cancer.

Bone Density↗
PubMedDate not supplied

Selective estrogen receptor modulators: a new category of compounds to extend postmenopausal women's health.

Selective estrogen receptor modulators (SERMs) are a new category of therapeutic agents, which bind with high affinity to estrogen receptors and mimic the effect of estrogens in some tissues but act as estrogen antagonists in others. Tamoxifen, a triphenylethylene derivative, was the first clinically available SERM. It is a potent anti-estrogen in the breast, and its use in breast cancer patients has made it the most widely prescribed antineoplastic drug worldwide. It has estrogen-like activity on bone metabolism, as well as cholesterol reduction. However, its ability to produce proliferation, and polyp formation, and even carcinomas, in the endometrium is well known. A new SERM, raloxifene, a benzothiopene derivative, has a clinical profile similar to tamoxifen's. However, preclinical as well as clinical studies reveal that unlike tamoxifen it is a pure anti-estrogen in the uterus. It has recently been FDA approved for prevention of osteoporosis in postmenopausal women. This report reviews pertinent preclinical and currently available clinical studies about this new SERM and discusses clinical applicability.

Bone Density↗