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 #
4P50HD073063-05
Application #
9126999
Study Section
Special Emphasis Panel (ZRG1-EMNR-Q)
Project Start
Project End
Budget Start
2016-06-01
Budget End
2017-05-31
Support Year
5
Fiscal Year
2016
Total Cost
$462,237
Indirect Cost
$159,457
Name
University of Colorado Denver
Department
Type
DUNS #
041096314
City
Aurora
State
CO
Country
United States
Zip Code
80045
Gavin, Kathleen M; Kohrt, Wendy M; Klemm, Dwight J et al. (2018) Modulation of Energy Expenditure by Estrogens and Exercise in Women. Exerc Sport Sci Rev 46:232-239
MacLean, Paul S; Rothman, Alexander J; Nicastro, Holly L et al. (2018) The Accumulating Data to Optimally Predict Obesity Treatment (ADOPT) Core Measures Project: Rationale and Approach. Obesity (Silver Spring) 26 Suppl 2:S6-S15
Rynders, Corey A; Schmidt, Stacy L; Bergouignan, Audrey et al. (2018) Effects of short-term sex steroid suppression on dietary fat storage patterns in healthy males. Physiol Rep 6:
Gavin, Kathleen M; Sullivan, Timothy M; Kohrt, Wendy M et al. (2018) Ovarian Hormones Regulate the Production of Adipocytes From Bone Marrow-Derived Cells. Front Endocrinol (Lausanne) 9:276
Hildreth, Kerry L; Ozemek, Cemal; Kohrt, Wendy M et al. (2018) Vascular dysfunction across the stages of the menopausal transition is associated with menopausal symptoms and quality of life. Menopause 25:1011-1019
Lanaspa, Miguel A; Kuwabara, Masanari; Andres-Hernando, Ana et al. (2018) High salt intake causes leptin resistance and obesity in mice by stimulating endogenous fructose production and metabolism. Proc Natl Acad Sci U S A 115:3138-3143
Perreault, Leigh; Newsom, Sean A; Strauss, Allison et al. (2018) Intracellular localization of diacylglycerols and sphingolipids influences insulin sensitivity and mitochondrial function in human skeletal muscle. JCI Insight 3:
Melanson, Edward L; Lyden, Kate; Gibbons, Ellie et al. (2018) Influence of Estradiol Status on Physical Activity in Premenopausal Women. Med Sci Sports Exerc 50:1704-1709
Gavin, Kathleen M; Shea, Karen L; Gibbons, Ellie et al. (2018) Gonadotropin-releasing hormone agonist in premenopausal women does not alter hypothalamic-pituitary-adrenal axis response to corticotropin-releasing hormone. Am J Physiol Endocrinol Metab 315:E316-E325
Foright, R M; Presby, D M; Sherk, V D et al. (2018) Is regular exercise an effective strategy for weight loss maintenance? Physiol Behav 188:86-93

Showing the most recent 10 out of 53 publications