Evaluation of bazedoxifene/conjugated estrogens for the treatment of menopausal symptoms and effects on metabolic parameters and overall safety profile

Løbo, Rogerio A.; Pinkerton, JoAnn V.; Gass, Margery; Dorin, Maxine H.; Ronkin, Sheila; Pickar, James H.; Constantine, Ginger D.

doi:10.1016/j.fertnstert.2009.03.113

Cited by 235 publications

(294 citation statements)

References 19 publications

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“…Findings from two large clinical trials recorded that bazedoxifene 20 mg/CE (0.45 mg or 0.625 mg) significantly improved vaginal atrophy with no endometrial safety signals (low rates, <1%, of endometrial hyperplasia which was similar to placebo) Lobo et al 2009]. Other trials also supported the benefits of bazedoxifene in improving vaginal maturation index, vaginal pH, vaginal dryness and reduction of most bothersome vaginal symptoms (p < 0.05) [Kagan et al 2010].…”

Section: Selective Estrogen Receptor Modulatorsmentioning

confidence: 96%

A clinical guide to the management of genitourinary symptoms in breast cancer survivors on endocrine therapy

et al. 2017

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There is increasing attention and concern about managing the adverse effects of adjuvant endocrine therapy for women with early breast cancer as the side effects of therapy influence compliance and can impair quality of life (QoL). Most side effects associated with tamoxifen (TAM) and aromatase inhibitors (AIs) are directly related to estrogen deprivation, and the symptoms are similar to those experienced during natural menopause but appear to be more severe than that seen in the general population. Prolonged estrogen deprivation may lead to atrophy of the vulva, vagina, lower urinary tract and supporting pelvic structures, resulting in a range of genitourinary symptoms that can in turn lead to pain, discomfort, impairment of sexual function and negatively impact on multiple domains of QoL. The genitourinary side effects may be prevented, reduced and managed in most cases but this requires early recognition and appropriate treatment. We provide an overview of practical clinical approaches to understanding the pathophysiology and the management of genitourinary symptoms in postmenopausal women receiving adjuvant endocrine therapy for breast cancer.

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Section: Selective Estrogen Receptor Modulatorsmentioning

confidence: 96%

A clinical guide to the management of genitourinary symptoms in breast cancer survivors on endocrine therapy

et al. 2017

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“…It has been suggested that a reasonable approach would be a selective estrogen receptor modulator (SERM) that binds to estrogen receptors alpha and beta with high affinity and acts either as an estrogen agonist or antagonist depending on the target tissue 9 . Phase III clinical trials evaluating the new third-generation SERM, bazedoxifene acetate (BZA), have shown promising results in the treatment of osteoporosis, and in combination with CEE for the reduction of menopausal symptoms and prevention of osteoporosis 10-13 .…”

Section: Introductionmentioning

confidence: 99%

Effects of bazedoxifene alone and with conjugated equine estrogens on coronary and peripheral artery atherosclerosis in postmenopausal monkeys

Clarkson

Ethun²,

Chen³

et al. 2013

Menopause

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Objective The objective was to evaluate the effects of bazedoxifene acetate (BZA), a new selective estrogen receptor modulator, on coronary and peripheral artery atherosclerosis and to determine if it would antagonize the atheroprotective effects of conjugated equine estrogens (CEE) in a monkey model. Methods Ninety-eight surgically postmenopausal monkeys (Macaca fascicularis) were fed a moderately atherogenic diet and then randomized to receive no treatment, or women’s equivalent doses of BZA (20 mg/day), CEE (0.45 mg/day) or BZA+CEE. The experiment period was for 20 months (approximately equivalent to 5 years of patient experience) during which interim measures were made of cardiovascular risk factors. At the end of the experimental period, the extent and severity of coronary and iliac artery atherosclerosis was quantified. Results Body weight, adiposity, fasting glucose concentrations and plasma lipid profiles were not different among treatment conditions. BZA had no adverse effects on coronary artery nor common iliac artery atherosclerosis extent or severity when compared to no-treatment. CEE, administered soon after inducing menopause, had a robust atheroprotective effect on both iliac and coronary artery extent and severity. The addition of BZA to the CEE treatment antagonized the atheroprotective effect of the CEE. Conclusions In this nonhuman primate trial, treatment with BZA alone, CEE alone and BZA and CEE in combination did not have significant effects on plasma lipid profiles. CEE markedly inhibited the progression and complication of both coronary and iliac artery atherosclerosis. BZA had no adverse effects on atherosclerosis but attenuated the atheroprotective effects of CEE.

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“…Both preclinical and clinical studies demonstrated that bazedoxifene is more tissue selective than other SERMs in the context of their agonistic and antagonistic activity on estrogen target tissues [110]. Bazedoxifene-CE combination therapy in postmenopausal women and rodents results in a significant increase in bone mineral density [111,112] and a decrease in the frequency of hot flashes [113,114] while protecting the endometrium. In a postmenopausal monkey model, this TSEC treatment did not affect the adiposity and plasma lipid profile, but bazedoxifene was found to attenuate the atheroprotective effects of CE [115].…”

Section: Estrogens Adipocytokines and Metabolic Syndromesmentioning

confidence: 99%

The role of estrogen in adipose tissue metabolism: insights into glucose homeostasis regulation [Review]

2014

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Abstract. Adipose tissue is an organ with active endocrine function involved in the regulation of energy balance and glucose homeostasis via multiple metabolic signaling pathways targeting the brain, liver, skeletal muscle, pancreas, and other organs. There is increasing evidence demonstrating that the female sex hormone, estrogen, regulates adipose development and improves systemic glucose homeostasis in both males and females. The underlying mechanism linking estrogenic regulation in adipose tissue and systemic glucose metabolism has not been fully elucidated, but is thought to include interactions of estrogen receptor signaling events involving lipolytic and/or lipogenic enzyme activity, free fatty acid metabolism, and adipocytokine production. Thus, understanding the effects of estrogen replacement on adipose tissue biology and metabolism is important in determining the risk of developing obesity-related metabolic disorders in patients undergoing treatment for sex hormone deficiency. In this report, we review literature regarding the role of estrogens and their corresponding receptors in the control of adipose metabolism and glucose homeostasis in both rodents and humans. We also discuss the effects of selective estrogen receptor modulators on glucose metabolism. Key words: Estrogen, Adipose tissue, Glucose homeostasis, Estrogen receptors, Selective estrogen receptor modulatorsIT HAS BEEN WELL established that adipose tissue is a dynamic tissue which is involved in the regulation of glucose and lipid metabolism, energy homeostasis and inflammation. In addition, adipose tissue is a complex and highly active endocrine organ that is a major site of sex steroid metabolism and production of bioactive adipokines that act at both the local (autocrine/ paracrine) and systemic (endocrine) level [1]. Thus, a functional failure of adipose tissue can cause changes in systemic energy delivery, impair glucose consumption, and affect the activation of self-regulatory mechanisms that regulate the whole body homeostasis system [2]. In addition, assessing the regional distribution of adipose tissue is critical during clinical examination of patients, particularly if they are obese [3]. The multiple endocrine abnormalities found in abdominal visceral obesity are more pronounced than in other obesity phenotypes [3].At menopause, women begin to develop increased amounts of visceral fat with redistribution of body fat. The risk of developing obesity-related diseases is significantly lower in premenopausal women than that in men, but not anymore after menopause, indicating the significant role of the female estrogen hormone in adipogenesis and adipose metabolism [4]. Furthermore, since adipose tissue serves as a crucial integrator of glucose homeostasis, estrogen deficiency strongly contributes to impaired glucose metabolism and the development of type 2 diabetes accompanied by abnormal adipose function. In fact, visceral adiposity is associated with postmenopausal women and ovariectomized (OVX) rodents, a condition that can be re...

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Evaluation of bazedoxifene/conjugated estrogens for the treatment of menopausal symptoms and effects on metabolic parameters and overall safety profile

Cited by 235 publications

References 19 publications

A clinical guide to the management of genitourinary symptoms in breast cancer survivors on endocrine therapy

A clinical guide to the management of genitourinary symptoms in breast cancer survivors on endocrine therapy

Effects of bazedoxifene alone and with conjugated equine estrogens on coronary and peripheral artery atherosclerosis in postmenopausal monkeys

The role of estrogen in adipose tissue metabolism: insights into glucose homeostasis regulation [Review]

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