A randomized, placebo- and active-controlled trial of bazedoxifene/conjugated estrogens for treatment of moderate to severe vulvar/vaginal atrophy in postmenopausal women

Kagan, Risa; Williams, Robert; Pan, Kaijie; Mirkin, Sebastián; Pickar, James H.

doi:10.1097/gme.0b013e3181b7c65f

Cited by 173 publications

(155 citation statements)

References 21 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]. Despite these findings BZA/CE has not been registered for the treatment of VVA associated with menopause and no studies have investigated drug safety in breast cancer survivors; therefore, it should not be recommended in women with breast cancer.…”

Section: Selective Estrogen Receptor Modulatorsmentioning

confidence: 61%

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: 61%

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

et al. 2017

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“…BZA also significantly reduces the risk of new vertebral fractures in postmenopausal women with osteoporosis compared with placebo (Silverman et al, 2008). In addition, recent studies indicate that BZA combined with conjugated estrogens relieves hot flashes and improves vulvovaginal atrophy and its symptoms (Kagan et al, 2010).…”

Section: Introductionmentioning

confidence: 94%

The Selective Estrogen Receptor Modulator Bazedoxifene Inhibits Hormone-Independent Breast Cancer Cell Growth and Down-Regulates Estrogen Receptor α and Cyclin D1

Lewis-Wambi¹,

Kim²,

Curpăn³

et al. 2011

Mol Pharmacol

117

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Bazedoxifene (BZA) is a third-generation selective estrogen receptor modulator (SERM) that has been approved for the prevention and treatment of postmenopausal osteoporosis. It has antitumor activity; however, its mechanism of action remains unclear. In the present study, we characterized the effects of BZA and several other SERMs on the proliferation of hormone-dependent MCF-7 and T47D breast cancer cells and hormone-independent MCF-7:5C and MCF-7:2A cells and examined its mechanism of action in these cells. We found that all of the SERMs inhibited the growth of MCF-7, T47D, and MCF-7:2A cells; however, only BZA and fulvestrant (FUL) inhibited the growth of hormone-independent MCF-7:5C cells. Cell cycle analysis revealed that BZA and FUL induced G 1 blockade in MCF-7:5C cells; however, BZA down-regulated cyclin D1, which was constitutively overexpressed in these cells, whereas FUL suppressed cyclin A. Further analysis revealed that small interfering RNA knockdown of cyclin D1 reduced the basal growth of MCF-7:5C cells, and it blocked the ability of BZA to induce G 1 arrest in these cells. BZA also down-regulated estrogen receptor-␣ (ER␣) protein by increasing its degradation and suppressing cyclin D1 promoter activity in MCF-7:5C cells. Finally, molecular modeling studies demonstrated that BZA bound to ER␣ in an orientation similar to raloxifene; however, a number of residues adopted different conformations in the induced-fit docking poses compared with the experimental structure of ER␣-raloxifene. Together, these findings indicate that BZA is distinct from other SERMs in its ability to inhibit hormone-independent breast cancer cell growth and to regulate ER␣ and cyclin D1 expression in resistant cells.

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“…In particular, gene expression analysis via microarray experiments have revealed that a subset of CEinducible genes were antagonized by bazedoxifene alone or in combination with CE (Chang et al, 2010b). The combination of bazedoxifene and CE [BZA-CE; or tissue-selective estrogen complex (TSEC)] displays efficacy and was determined to be safe in treating menopausal symptoms, decreasing bone turnover and bone loss in postmenopausal women at risk for osteoporosis, and treating vulvar/vaginal atrophy (Lindsay et al, 2009;Lobo et al, 2009;Utian et al, 2009;Bachmann et al, 2010;Kagan et al, 2010).…”

Section: Nuclear Receptors and Their Selective Modulatorsmentioning

confidence: 99%

Nuclear Receptors and Their Selective Pharmacologic Modulators

et al. 2013

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A randomized, placebo- and active-controlled trial of bazedoxifene/conjugated estrogens for treatment of moderate to severe vulvar/vaginal atrophy in postmenopausal women

Abstract: BZA/CE is effective in treating moderate to severe VVA and vaginal symptoms. These data further support the use of a tissue-selective estrogen complex containing BZA/CE as a new menopausal therapy for postmenopausal women.

Cited by 173 publications

References 21 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

The Selective Estrogen Receptor Modulator Bazedoxifene Inhibits Hormone-Independent Breast Cancer Cell Growth and Down-Regulates Estrogen Receptor α and Cyclin D1

Nuclear Receptors and Their Selective Pharmacologic Modulators

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