Effect of selective estrogen receptor modulators on metabolic homeostasis

• Published in: Biochimie 2016-05, Vol.124, p.92-97
• Main Authors: Xu, Beibei, Lovre, Dragana, Mauvais-Jarvis, Franck
• Format: Article
• Language: English
• Subjects: Animals; Bazedoxifene; Breast - metabolism; Breast - pathology; Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Diabetes; Diabetes Mellitus, Type 2 - metabolism; Diabetes Mellitus, Type 2 - pathology; Disease Models, Animal; Energy metabolism; Estrogens - metabolism; Female; Humans; Indoles - therapeutic use; Metabolic syndrome; Metabolic Syndrome - drug therapy; Metabolic Syndrome - metabolism; Metabolic Syndrome - pathology; Osteoporosis, Postmenopausal - drug therapy; Osteoporosis, Postmenopausal - metabolism; Osteoporosis, Postmenopausal - pathology; Receptors, Estrogen - metabolism; Selective estrogen receptor modulators; Tissue-selective estrogen complex; Uterus - metabolism; Uterus - pathology
• ISSN: 0300-9084; 1638-6183
• DOI: 10.1016/j.biochi.2015.06.018

Selective estrogen receptor modulators (SERMs) are estrogen receptor (ER) ligands that exhibit either estrogen agonistic or antagonistic activity in a tissue-specific manner. The first and second generation SERMs, tamoxifen and raloxifene, are used for treatment of ER positive breast cancer and postmenopausal osteoporosis respectively. The third-generation SERM, bazedoxifene (BZA), effectively prevents osteoporosis while blocking the estrogenic stimulation in breast and uterus. Notably, BZA combined with conjugated estrogens (CE) in a tissue-selective estrogen complex (TSEC) is a new menopausal treatment. Postmenopausal estrogen deficiency predisposes to metabolic syndrome and type 2 diabetes, and therefore the effects of SERMs and TSECs on metabolic homeostasis are gaining attention. In this article, we summarize current knowledge about the impact of SERMs on metabolic homeostasis and metabolic disorders in animal models and postmenopausal women. •SERMs exhibit tissue-specific estrogen agonistic or antagonistic activity.•The SERMs include tamoxifen, raloxifene and bazedoxifene.•Tamoxifen predisposes to diabetes, lipid abnormalities and hepatic steatosis.•Raloxifene exhibits minor effects on metabolic homeostasis.•Bazedoxifene combined with conjugated estrogens prevents menopausal metabolic dysfunction in mice.