These studies will explore mechanisms by which hormone replacement therapy (HRT) attenuates visceral fat accumulation in older women. Since visceral fat is a risk factor for cardiovascular disease, mechanisms of visceral fat attenuation may explain some of the cardioprotective benefits of HRT. The hypothesized mechanisms of visceral fat modulation by HRT are via 1) an attenuating effect on stress-induced hypothalamic- pituitary-adrenal (HPA) axis activity, and 2) an increase in sex- hormone binding globulin (SHBG) resulting in decreased free testosterone. Postmenopausal women will be randomized to HRT alone, placebo alone, HRT plus weight loss, or placebo plus weight loss. Measurement of stress-induced HPA axis activity, sex hormone levels, and visceral fat by computed tomography will be conducted at baseline and at 6 months.
The specific aims are to determine whether 1) HPA axis hyperactivity is associated with visceral obesity, 2) HRT attenuates stress-induced activity of the HPA axis in weight-stable women, 3) HRT-induced attenuation of HPA axis activity augments visceral fat loss during a period of weight reduction, 4) visceral fat loss attenuates HPA axis activity independent of HRT, and 5) HRT-induced increases in SHBG and decreases in free testosterone are directly related to changes in visceral adiposity.
| Van Pelt, R E; Gozansky, W S; Wolfe, P et al. (2014) Estrogen or raloxifene during postmenopausal weight loss: adiposity and cardiometabolic outcomes. Obesity (Silver Spring) 22:1024-31 |
| Van Pelt, Rachael E; Jankowski, Catherine M; Gozansky, Wendolyn S et al. (2011) Sex differences in the association of thigh fat and metabolic risk in older adults. Obesity (Silver Spring) 19:422-8 |
| Villalon, Karen L; Gozansky, Wendolyn S; Van Pelt, Rachael E et al. (2011) A losing battle: weight regain does not restore weight loss-induced bone loss in postmenopausal women. Obesity (Silver Spring) 19:2345-50 |
| Jankowski, Catherine M; Gozansky, Wendolyn S; Van Pelt, Rachael E et al. (2011) Oral dehydroepiandrosterone replacement in older adults: effects on central adiposity, glucose metabolism and blood lipids. Clin Endocrinol (Oxf) 75:456-63 |
| Jankowski, Catherine M; Gozansky, Wendolyn S; Van Pelt, Rachael E et al. (2008) Relative contributions of adiposity and muscularity to physical function in community-dwelling older adults. Obesity (Silver Spring) 16:1039-44 |
| Jankowski, Catherine M; Gozansky, Wendolyn S; Kittelson, John M et al. (2008) Increases in bone mineral density in response to oral dehydroepiandrosterone replacement in older adults appear to be mediated by serum estrogens. J Clin Endocrinol Metab 93:4767-73 |
| Van Pelt, Rachael E; Gozansky, Wendolyn S; Hickner, Robert C et al. (2006) Acute modulation of adipose tissue lipolysis by intravenous estrogens. Obesity (Silver Spring) 14:2163-72 |
| Van Pelt, R E; Jankowski, C M; Gozansky, W S et al. (2005) Lower-body adiposity and metabolic protection in postmenopausal women. J Clin Endocrinol Metab 90:4573-8 |
| Gozansky, W S; Lynn, J S; Laudenslager, M L et al. (2005) Salivary cortisol determined by enzyme immunoassay is preferable to serum total cortisol for assessment of dynamic hypothalamic--pituitary--adrenal axis activity. Clin Endocrinol (Oxf) 63:336-41 |
| Van Pelt, R E; Gozansky, W S; Schwartz, R S et al. (2003) Intravenous estrogens increase insulin clearance and action in postmenopausal women. Am J Physiol Endocrinol Metab 285:E311-7 |
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