Gonadal aging plays a distinct role in mediating some of the biological changes ascribed to the aging process. An example of this is the accelerated bone loss due to ovarian failure at the time of the menopause, which can be effectively mitigated with restoration of estrogens until other non-gonadal aging factors trigger a decline. Because it is difficult to isolate the consequences of gonadal aging from chronologic aging, it is not clear to what extent the loss of gonadal function increases risk for age-related diseases other than osteoporosis. There is compelling evidence from studies of female and male animals that the loss of gonadal function causes a dramatic decline of 30% to 80% in spontaneous physical activity. In females, but not males, this leads to accelerated weight gain, a marked increase in abdominal fat, and metabolic dysfunction. One prospective study of women followed through the menopausal transition suggests that physical activity and the maintenance of energy balance are also regulated by gonadal function in humans. In this context, the primary goal of the UCAMC SCOR clinical project is to use a controlled intervention approach to determine whether the suppression of ovarian function in women approaching the menopause causes a marked decline in physical activity. Additional goals are to assess changes in other components of energy expenditure, determine whether the disruption of energy balance is associated with changes in biomarkers of disease risk, and determine whether programmed exercise can prevent these changes. To achieve these aims, 66 women aged 45 to 50 years with normal menstrual cycle function will be randomized to receive 6 months of placebo, gonadotropin releasing hormone agonist (GnRHAc), or GnRHAG+exercise intervention. The primary outcome will be physical activity energy expenditure (PAEE), calculated from total daily energy expediture (TEE;by doubly-labeled water) with adjustment for the thermic effect of food and resting EE (REE;by indirect calorimetry). The global hypothesis is that the suppression of ovarian function with GnRHAG in women will cause a decrease in TEE due to decreased PAEE and, possibly, a decrease in REE.

Public Health Relevance

A decline in PAEE secondary to the loss of gonadal function could have diverse adverse effects on health because low physical activity is associated with all-cause mortality, coronary heart disease, stroke, type 2 diabetes, certain cancers, depression, etc. Moreover, this would be expected to have a greater adverse effect in women than in men, because the loss of gonadal function occurs at an earlier age in women.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Specialized Center (P50)
Project #
5P50HD073063-02
Application #
8548384
Study Section
Special Emphasis Panel (ZRG1-EMNR-Q)
Project Start
Project End
Budget Start
2013-06-01
Budget End
2014-05-31
Support Year
2
Fiscal Year
2013
Total Cost
$471,650
Indirect Cost
$157,424
Name
University of Colorado Denver
Department
Type
DUNS #
041096314
City
Aurora
State
CO
Country
United States
Zip Code
80045
Barbour, L A; Hernandez, T L; Reynolds, R M et al. (2016) Striking differences in estimates of infant adiposity by new and old DXA software, PEAPOD and skin-folds at 2 weeks and 1 year of life. Pediatr Obes 11:264-71
Hernandez, Teri L; Van Pelt, Rachael E; Anderson, Molly A et al. (2016) Women With Gestational Diabetes Mellitus Randomized to a Higher-Complex Carbohydrate/Low-Fat Diet Manifest Lower Adipose Tissue Insulin Resistance, Inflammation, Glucose, and Free Fatty Acids: A Pilot Study. Diabetes Care 39:39-42
Giles, Erin D; Steig, Amy J; Jackman, Matthew R et al. (2016) Exercise Decreases Lipogenic Gene Expression in Adipose Tissue and Alters Adipocyte Cellularity during Weight Regain After Weight Loss. Front Physiol 7:32
Rudolph, Michael C; Young, Bridget E; Jackson, Kristina Harris et al. (2016) Human Milk Fatty Acid Composition: Comparison of Novel Dried Milk Spot Versus Standard Liquid Extraction Methods. J Mammary Gland Biol Neoplasia 21:131-138
Melanson, Edward L; Gavin, Kathleen M; Shea, Karen L et al. (2015) Regulation of energy expenditure by estradiol in premenopausal women. J Appl Physiol (1985) 119:975-81
Pereira, R I; Casey, B A; Swibas, T A et al. (2015) Timing of Estradiol Treatment After Menopause May Determine Benefit or Harm to Insulin Action. J Clin Endocrinol Metab 100:4456-62
Van Pelt, Rachael E; Gavin, Kathleen M; Kohrt, Wendy M (2015) Regulation of Body Composition and Bioenergetics by Estrogens. Endocrinol Metab Clin North Am 44:663-76
Hernandez, Teri L; Bessesen, Daniel H; Cox-York, Kimberly A et al. (2015) Femoral lipectomy increases postprandial lipemia in women. Am J Physiol Endocrinol Metab 309:E63-71
Shea, Karen L; Gavin, Kathleen M; Melanson, Edward L et al. (2015) Body composition and bone mineral density after ovarian hormone suppression with or without estradiol treatment. Menopause 22:1045-52
Bessesen, Daniel H; Cox-York, Kimberly A; Hernandez, Teri Lynn et al. (2015) Postprandial triglycerides and adipose tissue storage of dietary fatty acids: impact of menopause and estradiol. Obesity (Silver Spring) 23:145-53

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