Postmenopausal estrogen replacement therapy (ERT) has become an accepted intervention in aging women. The recent publication of the Heart and Estrogen and Progestin Replacement Study (HERS) has made the difficult decision to initiate postmenopausal ERT even more difficult for clinicians. Both small, dense low density lipoprotein (LDL) and plasminogen activator inhibitor Type 1 (PAI-1) are risk factors for coronary artery disease (CAD) that increase with menopause and may represent markers of future individual CAD risk. The primary objective of the proposed study is to investigate whether women who develop small, dense LDL across the menopause will selectively benefit from transdermal ERT. The mechanisms underlying the changes in LDL size will also be studied by measuring hepatic lipase activity, cholesteryl ester transfer protein (CETP) activity, triglyceride (TG) levels, body fat distribution and the hepatic lipase gene promoter polymorphism, all known to affect LDL size. The investigators will also determine whether women who develop small, dense LDL with menopause also have elevated PAI-1. This is a prospective, randomized non-blinded crossover trial comparing oral and transdermal ERT in two groups of postmenopausal women who have been followed since the premenopausal state. Twenty-three postmenopausal women who have developed small, dense LDL with menopause will be compared to 23 postmenopausal women who remain with large, buoyant LDL. They will be randomized to a six-month course of transdermal or oral ERT followed by a six-month washout period before the start of the second ERT course. This study will determine if there is a preferred method of postmenopausal ERT in the subset of women who develop small, dense LDL after menopause. They will also elucidate the mechanisms that underlie the shifts in LDL size with oral and transdermal ERT.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23RR016067-02
Application #
6394868
Study Section
National Center for Research Resources Initial Review Group (RIRG)
Program Officer
Wilde, David B
Project Start
2000-08-01
Project End
2005-06-30
Budget Start
2001-07-01
Budget End
2002-06-30
Support Year
2
Fiscal Year
2001
Total Cost
$125,010
Indirect Cost
Name
University of Washington
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195
Lee, Christine G; Carr, Molly C; Murdoch, Susan J et al. (2009) Adipokines, inflammation, and visceral adiposity across the menopausal transition: a prospective study. J Clin Endocrinol Metab 94:1104-10
Woods, Nancy F; Carr, Molly C; Tao, Eunice Y et al. (2006) Increased urinary cortisol levels during the menopausal transition. Menopause 13:212-21
Turgeon, Judith L; Carr, Molly C; Maki, Pauline M et al. (2006) Complex actions of sex steroids in adipose tissue, the cardiovascular system, and brain: Insights from basic science and clinical studies. Endocr Rev 27:575-605
Carr, Molly C; Knopp, Robert H; Brunzell, John D et al. (2005) Effect of raloxifene on serum triglycerides in women with a history of hypertriglyceridemia while on oral estrogen therapy. Diabetes Care 28:1555-61
Carr, Molly C; Brunzell, John D; Deeb, Samir S (2004) Ethnic differences in hepatic lipase and HDL in Japanese, black, and white Americans: role of central obesity and LIPC polymorphisms. J Lipid Res 45:466-73
Carr, Molly C; Brunzell, John D (2004) Abdominal obesity and dyslipidemia in the metabolic syndrome: importance of type 2 diabetes and familial combined hyperlipidemia in coronary artery disease risk. J Clin Endocrinol Metab 89:2601-7
Meyers, C Daniel; Carr, Molly C; Park, Sang et al. (2003) Varying cost and free nicotinic acid content in over-the-counter niacin preparations for dyslipidemia. Ann Intern Med 139:996-1002
Carr, M C; Ayyobi, A F; Murdoch, S J et al. (2002) Contribution of hepatic lipase, lipoprotein lipase, and cholesteryl ester transfer protein to LDL and HDL heterogeneity in healthy women. Arterioscler Thromb Vasc Biol 22:667-73
Murdoch, Susan J; Carr, Molly C; Kennedy, Hal et al. (2002) Selective and independent associations of phospholipid transfer protein and hepatic lipase with the LDL subfraction distribution. J Lipid Res 43:1256-63
Murdoch, Susan J; Wolfbauer, Gertrud; Kennedy, Hal et al. (2002) Differences in reactivity of antibodies to active versus inactive PLTP significantly impacts PLTP measurement. J Lipid Res 43:281-9

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