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      Estriol : emerging clinical benefits

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      Menopause
      Ovid Technologies (Wolters Kluwer Health)

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          Abstract

          Estriol is the main estrogen in pregnancy, but has received less attention outside gestation. It is well known that pregnancy has an immunosuppressive effect on many autoimmune diseases such as multiple sclerosis, psoriasis, thyroiditis, uveitis, and rheumatoid arthritis. Emerging evidence indicates that estriol has potential immunomodulatory benefits for many disease states including autoimmune, inflammatory, and neurodegenerative conditions. In this review, we discuss emerging roles for estriol in the treatment of menopausal symptoms, osteoporosis, cancer, hyperlipidemia, vascular disease, and multiple sclerosis. Estriol appears to offer a potentially cost-effective approach to a variety of conditions and may offer a wide range of health benefits.

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          Most cited references55

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          Source of estrogen production in postmenopausal women.

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            Estriol acts as a GPR30 antagonist in estrogen receptor-negative breast cancer cells.

            Estrogens are structurally related steroids that regulate important physiological processes. 17beta-estradiol (E2) is reversibly oxidized to estrone (E1) and both E2 and E1 can be irreversibly converted to estriol (E3), which also originates directly from androstenedione. The action of E2 has been traditionally explained by the binding to the estrogen receptor (ER) alpha and ER beta, however the G protein-coupled receptor (GPR) 30 has been recently involved in the rapid signaling triggered by estrogens. Although the role of E2 in the development of breast cancer has been largely documented, the contribution of E3 still remains to be completely evaluated. Here, we demonstrate for the first time that E3 acts as a GPR30 antagonist since it was able to inhibit the GPR30-mediated responses such as the rapid ERK activation, the up-regulation of target genes like c-fos and connective tissue growth factor, the proliferative effects observed in ER-negative SkBr3 cells. (c) 2010 Elsevier Ireland Ltd. All rights reserved.
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              Back to the future: Hormone replacement therapy as part of a prevention strategy for women at the onset of menopause.

              In the late 1980s, several observational studies and meta-analyses suggested that hormone replacement therapy (HRT) was beneficial for prevention of osteoporosis, coronary heart disease, dementia and decreased all-cause mortality. In 1992, the American College of Physicians recommended HRT for prevention of coronary disease. In the late 1990s and early 2000s, several randomized trials in older women suggested coronary harm and that the risks, including breast cancer, outweighed any benefit. HRT stopped being prescribed at that time, even for women who had severe symptoms of menopause. Subsequently, reanalyzes of the randomized trial data, using age stratification, as well as newer studies, and meta-analyses have been consistent in showing that younger women, 50-59 years or within 10 years of menopause, have decreased coronary disease and all-cause mortality; and did not have the perceived risks including breast cancer. These newer findings are consistent with the older observational data. It has also been reported that many women who abruptly stopped HRT had more risks, including more osteoporotic fractures. The current data confirm a "timing" hypothesis for benefits and risks of HRT, showing that younger have many benefits and few risks, particularly if therapy is predominantly focused on the estrogen component. We discuss these findings and put into perspective the potential risks of treatment, and suggest that we may have come full circle regarding the use of HRT. In so doing we propose that HRT should be considered as part of a general prevention strategy for women at the onset of menopause.
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                Author and article information

                Journal
                Menopause
                Menopause
                Ovid Technologies (Wolters Kluwer Health)
                1072-3714
                2017
                September 2017
                : 24
                : 9
                : 1081-1085
                Article
                10.1097/GME.0000000000000855
                28375935
                d27c6904-3189-44d7-be64-04bde6b3455b
                © 2017
                History

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