The effect of selective estrogen receptor modulators on type 2 diabetes onset in women: Basic and clinical insights - PubMed (original) (raw)

Review

The effect of selective estrogen receptor modulators on type 2 diabetes onset in women: Basic and clinical insights

Beibei Xu et al. J Diabetes Complications. 2017 Apr.

Abstract

Selective estrogen receptor modulators (SERMs) are a class of compounds that interact with estrogen receptors (ERs) and exert agonist or antagonist effects on ERs in a tissue-specific manner. Tamoxifen, a first generation SERM, is used for treatment of ER positive breast cancer. Raloxifene, a second generation SERM, was used to prevent postmenopausal osteoporosis. The third-generation SERM bazedoxifene (BZA) effectively prevents osteoporosis while preventing estrogenic stimulation of breast and uterus. Notably, BZA combined with conjugated estrogens (CE) is a new menopausal treatment. The menopausal state predisposes to metabolic syndrome and type 2 diabetes, and therefore the effects of SERMs on metabolic homeostasis are gaining attention. Here, we summarize knowledge of SERMs' impacts on metabolic, homeostasis, obesity and diabetes in rodent models and postmenopausal women.

Keywords: Bazedoxifene; Diabetes; Energy metabolism; Metabolic syndrome; Selective estrogen receptor modulators; Steatosis.

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Figures

Figure 1. Summary of the effects of tamoxifen

Tamoxifen is an ER antagonist in breast and has estrogenic effects on bone and uterus. Tamoxifen decreases food intake, body weight and fat mass in rodents. It also lowers body weight in obese women. Tamoxifen decreases β-cell survival and proliferation in rodents and increases the incidence of diabetes in patients with breast cancer. Tamoxifen also promotes hepatic steatosis in rodents and women.

Figure 2. Summary of the effects of raloxifene

Raloxifene is an ER agonist in bone and acts as ER antagonist in breast. It has a neutral effect in uterus. Raloxifene reduced fat mass in OVX female rodents and prevented abdominal adiposity in postmenopausal women. Raloxifene’s effects on insulin sensitivity are controversial.

Figure 3. Summary of the effects of the combination bazedoxifene with CE

Bazedoxifene acts as an ER antagonist in breast and uterus while it is an ER agonist in bone. In rodent models of menopause, CE/BZA prevents obesity, reduces hepatic steatosis formation, and improves liver and muscle insulin sensitivity as well as glucose homeostasis.

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The effect of selective estrogen receptor modulators on type 2 diabetes onset in women: Basic and clinical insights - PubMed (original) (raw)