Abstract
Obese postmenopausal women have an increased risk of breast cancer and are likely to have a worse prognosis than nonobese postmenopausal women. The cessation of ovarian function after menopause results in withdrawal of ovarian sex steroid hormones, estrogen, and progesterone. Accumulating evidence suggests that the withdrawal of estrogen and progesterone causes homeostasis imbalances, including decreases in insulin sensitivity and leptin secretion and changes in glucose and lipid metabolism, resulting in a total reduction in energy expenditure. Together with a decrease in physical activity and consumption of a high fat diet, these factors significantly contribute to obesity in postmenopausal women. Obesity may contribute to breast cancer development through several mechanisms. Obesity causes localized inflammation, an increase in local estrogen production, and changes in cellular metabolism. In addition, obese women have a higher risk of insulin insensitivity, and an increase in insulin and other growth factor secretion. In this review, we describe our current understanding of the molecular actions of estrogen and progesterone and their contributions to cellular metabolism, obesity, inflammation, and postmenopausal breast cancer. We also discuss how modifications of estrogen and progesterone actions might be used as a therapeutic approach for obesity and postmenopausal breast cancer.
Highlights
The prevalence of obesity in many developed and developing countries has been increasing at an alarming rate reaching pandemic proportions over the past decade [1]
Prospective cohort studies showed about a twofold increase in breast cancer risk among postmenopausal women who had higher production of various sex steroid, including dehydroepiandrosterone sulfate (DHEAS), testosterone, estrone, and total estradiol (E2) and breast cancer risk was inversely correlated with the expression of steroid hormone binding globulin (SHBG) [8]
Recent evidence suggested that metabolic syndromes such as insulin resistance, hypertension, and hyperlipidemia increased the risk for postmenopausal breast cancer [11], suggesting a central role of ovarian sex steroids, estrogen, and progesterone, in regulating cellular metabolism, proliferation, and differentiation
Summary
The prevalence of obesity in many developed and developing countries has been increasing at an alarming rate reaching pandemic proportions over the past decade [1]. An increasing number of studies have highlighted the association between obesity and the risk of various cancers. Recent evidence suggested that metabolic syndromes such as insulin resistance, hypertension, and hyperlipidemia increased the risk for postmenopausal breast cancer [11], suggesting a central role of ovarian sex steroids, estrogen, and progesterone, in regulating cellular metabolism, proliferation, and differentiation. Loss of the ovarian function to supply estrogen and progesterone after menopause can cause deregulation of the body’s metabolism and inflammatory responses with increased risk of postmenopausal breast cancer. We will discuss and provide an integrated view of our current understanding of this complex relationship between ovarian sex steroids and their receptors in relation to obesity and inflammation and their contribution to postmenopausal breast cancer. Detailed molecular mechanisms of how ovarian sex steroids affect obesity and inflammation will be discussed
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