Loss of ovarian function accelerates the risk of cardiovascular and metabolic disease, and heralds the onset of changes that can have far-reaching consequences on women's future health. We will examine the impact of the menopause transition on several metabolic and cardiovascular risk factors associated with declining health status in women. Our overall hypothesis is that women who experience a natural menopause transition will show - accelerated decline in daily energy expenditure, increase in total and Intra-abdominal body fat and decline in insulin sensitivity. In this 5-year longitudinal study, we will recruit 57 premenopausal women and examine their natural history as they traverse the menopause. Changes in energy expenditure, body composition, body fat distribution and insulin sensitivity will be measured annually (a total of five exams) to examine the time course of menopause and age-related changes in outcome variables.
Our First Aim will examine the effects of the menopause transition on total daily energy expenditure, body fat distribution and insulin sensitivity. We will use: 1) doubly labeled water and indirect calorimetry to measure changes in total daily energy expenditure, resting metabolic rate, thermic effect of a meal and physical activity; 2) computerized tomography to assess changes in intra-abdominal body fat and 3) euglycemic clamps to measure insulin sensitivity.
Our Second Aim i s to develop and cross-validate new models to predict daily energy requirements, as derived from biological markers of total daily energy expenditure in pre- and postmenopausal women and to compare them to current daily energy intake recommendations. Current recommendations for daily energy needs are based on out- dated food intake data and have not considered the influence of menopause status, body composition and physical activity as determinants of daily energy needs. These limitations have led to the suggestion that prescription of daily energy requirements should be based on the measurement of total daily energy expenditure. Analyses of these data will characterize the biological and metabolic sequelae of changes in energy metabolism, body fat distribution and insulin sensitivity in women as they traverse the menopause. Furthermore, we will offer new guidelines to predict energy requirements during the menopause transition.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
1R01AG013978-01A1
Application #
2001936
Study Section
Special Emphasis Panel (ZRG4-ORTH (02))
Project Start
1997-09-15
Project End
2002-08-31
Budget Start
1997-09-15
Budget End
1998-08-31
Support Year
1
Fiscal Year
1997
Total Cost
Indirect Cost
Name
University of Vermont & St Agric College
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
066811191
City
Burlington
State
VT
Country
United States
Zip Code
05405
Toth, Michael J; Sites, Cynthia K; Matthews, Dwight E (2006) Role of ovarian hormones in the regulation of protein metabolism in women: effects of menopausal status and hormone replacement therapy. Am J Physiol Endocrinol Metab 291:E639-46
Toth, Michael J; Sites, Cynthia K; Poehlman, Eric T et al. (2002) Effect of menopausal status on lipolysis: comparison of plasma glycerol levels in middle-aged, premenopausal and early, postmenopausal women. Metabolism 51:322-6
Sites, Cynthia K; Toth, Michael J; Cushman, Mary et al. (2002) Menopause-related differences in inflammation markers and their relationship to body fat distribution and insulin-stimulated glucose disposal. Fertil Steril 77:128-35
Poehlman, Eric T (2002) Menopause, energy expenditure, and body composition. Acta Obstet Gynecol Scand 81:603-11
Brochu, M; Tchernof, A; Dionne, I J et al. (2001) What are the physical characteristics associated with a normal metabolic profile despite a high level of obesity in postmenopausal women? J Clin Endocrinol Metab 86:1020-5
Toth, M J; Sites, C K; Cefalu, W T et al. (2001) Determinants of insulin-stimulated glucose disposal in middle-aged, premenopausal women. Am J Physiol Endocrinol Metab 281:E113-21
DeNino, W F; Tchernof, A; Dionne, I J et al. (2001) Contribution of abdominal adiposity to age-related differences in insulin sensitivity and plasma lipids in healthy nonobese women. Diabetes Care 24:925-32
Toth, M J; Poehlman, E T; Matthews, D E et al. (2001) Effects of estradiol and progesterone on body composition, protein synthesis, and lipoprotein lipase in rats. Am J Physiol Endocrinol Metab 280:E496-501
Toth, M J; Tchernof, A; Sites, C K et al. (2000) Menopause-related changes in body fat distribution. Ann N Y Acad Sci 904:502-6
Tchernof, A; Poehlman, E T; Despres, J P (2000) Body fat distribution, the menopause transition, and hormone replacement therapy. Diabetes Metab 26:20-Dec

Showing the most recent 10 out of 22 publications