Tomas Vaisar1, Jennifer L Gordon2, Jake Wimberger1, Jay W Heinecke1, Alan L Hinderliter3, David R Rubinow2, Susan S Girdler2, Katya B Rubinow4. 1. Diabetes Institute, Division of Metabolism, Endocrinology, and Nutrition, Department of Medicine, University of Washington School of Medicine, 750 Republican St, Seattle WA 98109, USA. 2. Department of Psychiatry, University of North Carolina at Chapel Hill School of Medicine, 101 Manning Drive, Chapel Hill, NC 27599, USA. 3. Department of Medicine, University of North Carolina at Chapel Hill School of Medicine, 101 Manning Drive, Chapel Hill, NC 27599, USA. 4. Diabetes Institute, Division of Metabolism, Endocrinology, and Nutrition, Department of Medicine, University of Washington School of Medicine, 750 Republican St, Seattle WA 98109, USA. Electronic address: rubinow@uw.edu.
Abstract
BACKGROUND: The cardiovascular (CV) safety of estrogen replacement therapy (ERT) in perimenopausal women remains uncertain. Although exogenous estrogens increase HDL cholesterol (HDL-C), estrogen-mediated effects on alternative metrics of HDL that may better predict CV risk are unknown. OBJECTIVE: To determine the effects of transdermal ERT on HDL composition and cholesterol efflux capacity (CEC), as well as the relationships between these metrics and CV risk factors. METHODS: Fasting plasma samples were analyzed from 101 healthy, perimenopausal women randomized to receive either transdermal placebo or transdermal estradiol (100 μg/24 h) with intermittent micronized progesterone. At baseline and after 6 months of treatment, serum HDL CEC, HDL particle concentration, HDL protein composition, insulin resistance and brachial artery flow-mediated dilatation (FMD) were measured. RESULTS: No difference between groups was found for change in plasma HDL-C (p = 0.69). Between-group differences were found for changes in serum HDL total CEC [median change from baseline -5.4 (-17.3,+8.4)% ERT group versus +5.8 (-6.3,+16.9)% placebo group, p = 0.01] and ABCA1-specific CEC [median change from baseline -5.3 (-10.7,+6.7)% ERT group versus +7.4 (-1.5,+18.1)% placebo group, p = 0.0002]. Relative to placebo, transdermal ERT led to reductions in LDL-C (p < 0.0001) and insulin resistance (p = 0.0002). An inverse correlation was found between changes in serum HDL total CEC and FMD (β = -0.26, p = 0.004). CONCLUSIONS: Natural menopause leads to an increase in serum HDL CEC, an effect that is abrogated by transdermal ERT. However, transdermal ERT leads to favorable changes in major CV risk factors.
BACKGROUND: The cardiovascular (CV) safety of estrogen replacement therapy (ERT) in perimenopausal women remains uncertain. Although exogenous estrogens increase HDL cholesterol (HDL-C), estrogen-mediated effects on alternative metrics of HDL that may better predict CV risk are unknown. OBJECTIVE: To determine the effects of transdermal ERT on HDL composition and cholesterol efflux capacity (CEC), as well as the relationships between these metrics and CV risk factors. METHODS: Fasting plasma samples were analyzed from 101 healthy, perimenopausal women randomized to receive either transdermal placebo or transdermal estradiol (100 μg/24 h) with intermittent micronized progesterone. At baseline and after 6 months of treatment, serum HDL CEC, HDL particle concentration, HDL protein composition, insulin resistance and brachial artery flow-mediated dilatation (FMD) were measured. RESULTS: No difference between groups was found for change in plasma HDL-C (p = 0.69). Between-group differences were found for changes in serum HDL total CEC [median change from baseline -5.4 (-17.3,+8.4)% ERT group versus +5.8 (-6.3,+16.9)% placebo group, p = 0.01] and ABCA1-specific CEC [median change from baseline -5.3 (-10.7,+6.7)% ERT group versus +7.4 (-1.5,+18.1)% placebo group, p = 0.0002]. Relative to placebo, transdermal ERT led to reductions in LDL-C (p < 0.0001) and insulin resistance (p = 0.0002). An inverse correlation was found between changes in serum HDL total CEC and FMD (β = -0.26, p = 0.004). CONCLUSIONS: Natural menopause leads to an increase in serum HDL CEC, an effect that is abrogated by transdermal ERT. However, transdermal ERT leads to favorable changes in major CV risk factors.
Authors: Jennifer L Gordon; David R Rubinow; Tory A Eisenlohr-Moul; Kai Xia; Peter J Schmidt; Susan S Girdler Journal: JAMA Psychiatry Date: 2018-02-01 Impact factor: 21.596
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Authors: Nathalie Pamir; Patrick M Hutchins; Graziella E Ronsein; Hao Wei; Chongren Tang; Riku Das; Tomas Vaisar; Edward Plow; Volker Schuster; Marlys L Koschinsky; Catherine A Reardon; Richard Weinberg; David A Dichek; Santica Marcovina; Godfrey S Getz; Jay W Heinecke Journal: JCI Insight Date: 2017-08-03
Authors: Jee-Yeon Lee; Hye Sun Hyun; Hyang-Gi Park; Ji Hyun Seo; Eun Young Lee; Ji Soo Lee; Dong-Yun Lee; Doo Seok Choi; Byung-Koo Yoon Journal: J Menopausal Med Date: 2015-08-28