Hot flashes pose a significant public heath problem because they are the most common perimenopausal symptom reported by women in the United States and the primary reason that women seek medical care during the menopausal transition. Despite the public health importance of hot flashes, little is known about the factors that predispose women to hot flashes. During the previous funding period, new preliminary data were obtained that indicate that obesity increases the risk of perimenopausal hot flashes. Thus, the overall goal of this renewal application is to examine the mechanism by which obesity increases the risk of hot flashes. Specifically, the proposed work will test the hypothesis that obesity is associated with hot flashes through mechanisms that involve early ovarian failure, altered sex steroid hormone levels, and selected genetic polymorphisms in steroidogenic enzymes and steroid hormone receptors.
The specific aims are to determine whether: 1) obesity is associated with early ovarian follicle loss and altered levels of sex steroid hormones, 2) obesity is associated with selected polymorphisms in genes that encode enzymes that synthesize and degrade sex steroids and/or receptors that respond to sex steroids, 3) selected polymorph- isms are associated with sex steroid hormone levels, and 4) the association between obesity and hot flashes is mediated by early ovarian follicle loss, altered hormone levels, and/or selected genetic polymorphisms. To complete these aims, obese and non-obese perimenopausal women with and without hot flashes will complete questionnaires, receive transvaginal ultrasounds for measurement of ovarian volume and follicle numbers, and provide blood samples for measurement of selected sex steroid hormones and genetic polymorphisms in steroidogenic enzymes and steroid hormone receptors. Ovarian volume, follicle numbers, sex steroid hormone levels, and the odds of having selected genetic polymorphisms will be compared in obese and non-obese women using appropriate statistical tests. Further, statistical models will be used to determine whether the association between obesity and hot flashes is attenuated by adjustment for ovarian volume, follicle numbers, sex steroid hormone levels, and selected genetic polymorphisms. The results of this study will provide information about risk factors for perimenopausal hot flashes. In turn, this information may be useful for the future development of novel strategies to prevent or treat hot flashes.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG018400-09
Application #
8112665
Study Section
Infectious Diseases, Reproductive Health, Asthma and Pulmonary Conditions Study Section (IRAP)
Program Officer
Sherman, Sherry
Project Start
2000-07-01
Project End
2014-07-31
Budget Start
2011-08-01
Budget End
2014-07-31
Support Year
9
Fiscal Year
2011
Total Cost
$491,670
Indirect Cost
Name
University of Illinois Urbana-Champaign
Department
Veterinary Sciences
Type
Schools of Veterinary Medicine
DUNS #
041544081
City
Champaign
State
IL
Country
United States
Zip Code
61820
Ziv-Gal, Ayelet; Gallicchio, Lisa; Chiang, Catheryne et al. (2016) Phthalate metabolite levels and menopausal hot flashes in midlife women. Reprod Toxicol 60:76-81
Gallicchio, Lisa; Flaws, Jodi A; Smith, Rebecca L (2016) Age at menarche, androgen concentrations, and midlife obesity: findings from the Midlife Women's Health Study. Menopause 23:1182-1188
Gallicchio, Lisa; Miller, Susan R; Kiefer, Judith et al. (2016) The Associations Between Body Mass Index, Smoking, and Alcohol Intake with Ovarian Volume in Midlife Women. J Womens Health (Larchmt) 25:409-15
Montasser, May E; Ziv-Gal, Ayelet; Brown, Jessica P et al. (2015) A potentially functional variant in the serotonin transporter gene is associated with premenopausal and perimenopausal hot flashes. Menopause 22:108-13
Smith, Rebecca L; Flaws, Jodi A; Gallicchio, Lisa (2015) Does quitting smoking decrease the risk of midlife hot flashes? A longitudinal analysis. Maturitas 82:123-7
Gallicchio, Lisa; Miller, Susan R; Kiefer, Judith et al. (2015) Risk factors for hot flashes among women undergoing the menopausal transition: baseline results from the Midlife Women's Health Study. Menopause 22:1098-107
Gallicchio, Lisa; Miller, Susan R; Kiefer, Judith et al. (2014) Change in body mass index, weight, and hot flashes: a longitudinal analysis from the midlife women's health study. J Womens Health (Larchmt) 23:231-7
Ziv-Gal, Ayelet; Flaws, Jodi A; Mahoney, Megan M et al. (2013) Genetic polymorphisms in the aryl hydrocarbon receptor-signaling pathway and sleep disturbances in middle-aged women. Sleep Med 14:883-7
Nakano, Karen; Pinnow, Ellen; Flaws, Jodi A et al. (2012) Reproductive history and hot flashes in perimenopausal women. J Womens Health (Larchmt) 21:433-9
Ziv-Gal, Ayelet; Gallicchio, Lisa; Miller, Susan R et al. (2012) Genetic polymorphisms in the aryl hydrocarbon receptor signaling pathway as potential risk factors of menopausal hot flashes. Am J Obstet Gynecol 207:202.e9-202.e18

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