Many perimenopausal women experience hot flashes during mid-life. Hot flashes often have serious consequences, including fatigue, irritability, and acute physical discomfort that affects work and quality of life. Despite the high prevalence and importance of hot flashes, little is known about their risk factors. The proposed project will test the hypotheses that smoking, genetic polymorphisms in cytochrome P450 (CYP450) enzymes, and low serum estrogen levels are associated with an increased risk of hot flashes. It also will assess the hypothesis that smoking and CYP45O polymorphisms are associated with hot flashes via mechanisms that lower estrogen levels.
The specific aims are to: 1) determine whether cigarette smoking is associated with risk of hot flashes, 2) evaluate whether CYP45O polymorphisms are associated with risk of hot flashes, 3) assess whether low levels of serum estrogens are associated with risk of hot flashes, and 4) determine whether women exposed to both smoking and genetic polymorphisms have a different risk of hot flashes than women exposed to one or none of these risk factors. To complete the study, 400 perimenopausal women (45-54 years) with hot flashes (200 cases) or without hot flashes (200+ controls) will be recruited from Baltimore and the surrounding areas. Each participant will complete a questionnaire that assesses hot flash and smoking history, other potential risk factors, and potential confounders. Participants also will provide blood samples for analysis of estrogen levels and CYP450 genetic polymorphisms. Associations between hot flashes, smoking, estrogen levels, and CYP450 polymorphisms then will be assessed using appropriate statistical and analytic methods. The results of this study will provide information about risk factors for perimenopausal hot flashes, particularly the influence of smoking, CYP450 polymorphisms, and serum estrogen levels. These results ultimately may be useful for future studies on the prevention and/or treatment of hot flashes.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG018400-04
Application #
6757225
Study Section
Epidemiology and Disease Control Subcommittee 2 (EDC)
Program Officer
Sherman, Sherry
Project Start
2001-08-01
Project End
2006-07-31
Budget Start
2004-08-01
Budget End
2006-07-31
Support Year
4
Fiscal Year
2004
Total Cost
$333,672
Indirect Cost
Name
University of Maryland Baltimore
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
188435911
City
Baltimore
State
MD
Country
United States
Zip Code
21201
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
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
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
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
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
Ziv-Gal, Ayelet; Gallicchio, Lisa; Miller, Susan R et al. (2012) A genetic polymorphism in the CYP19A1 gene and the risk of hypertension among midlife women. Maturitas 71:70-5

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