The menopause transition is associated with a pronounced increase in risk of cardiovascular disease. Hormone replacement therapy in postmenopausal women reduces the risk of cardiovascular disease by approximately 50 percent, although the mechanisms involved are poorly understood. We will examine the impact of hormone replacement therapy on metabolic risk factors affecting cardiovascular disease and future health in aging women. Our overall hypothesis is that hormone replacement therapy in the early postmenopausal period reduces the central accumulation of body fat and improves insulin sensitivity, thereby reducing a metabolic risk factor for cardiovascular disease. A total of 88 women will be recruited for this 2-year randomized double-blinded placebo-controlled longitudinal study. We will measure outcomes of changes in body fat distribution and insulin sensitivity on 4 occasions (baseline, 6 months, 1 year and 2 years) in women taking continuous conjugated estrogens plus medroxyprogesterone acetate or placebo. Our study will provide new information on the temporal sequence of changes in outcome variables. We will use: 1) computerized tomography (CT) and dual photon x- ray absorptiometry (DEXA) scanning to measure intra-abdominal body fat and total body fat, and 2) euglycemic clamps to measure insulin sensitivity. Analysis of these data will provide an understanding of the impact of hormone replacement on the syndrome of central obesity and insulin resistance, which predisposes women to increased risk for cardiovascular disease. In addition, our study may allow physicians to target hormone replacement to women with specific body compositions.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29AG015121-04
Application #
6475611
Study Section
Special Emphasis Panel (ZRG4-SSS-G (02))
Program Officer
Sherman, Sherry
Project Start
1998-12-02
Project End
2003-11-30
Budget Start
2001-12-01
Budget End
2002-11-30
Support Year
4
Fiscal Year
2002
Total Cost
$108,093
Indirect Cost
Name
University of Vermont & St Agric College
Department
Obstetrics & Gynecology
Type
Schools of Medicine
DUNS #
066811191
City
Burlington
State
VT
Country
United States
Zip Code
05405
Cooper, Brian C; Burger, Natalie Z; Toth, Michael J et al. (2007) Insulin resistance with hormone replacement therapy: associations with markers of inflammation and adiposity. Am J Obstet Gynecol 196:123.e1-7
Goodrow, Gwen J; L'Hommedieu, Georgia D; Gannon, Barbara et al. (2006) Predictors of worsening insulin sensitivity in postmenopausal women. Am J Obstet Gynecol 194:355-61
Sites, Cynthia K; L'Hommedieu, Georgia D; Toth, Michael J et al. (2005) The effect of hormone replacement therapy on body composition, body fat distribution, and insulin sensitivity in menopausal women: a randomized, double-blind, placebo-controlled trial. J Clin Endocrinol Metab 90:2701-7
Sites, C K; L'Hommedieu, G D; Brochu, M et al. (2001) Previous exposure to hormone replacement therapy and confounders in metabolic studies. Menopause 8:281-5