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Obstetrics & Gynecology 2005;106:1372-1381
© 2005 by The American College of Obstetricians and Gynecologists
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ORIGINAL ARTICLES

Cytochrome Gene Polymorphisms, Serum Estrogens, and Hot Flushes in Midlife Women

Kala Visvanathan, MD, MHS1,2, Lisa Gallicchio, PhD1, Chrissy Schilling, MS3, Janice K. Babus3, Lynn M. Lewis, MA3, Susan R. Miller, ScD4, Howard Zacur, MD, PhD4 and Jodi A. Flaws, PhD3

From the 1Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health; 2Johns Hopkins Sidney Kimmel Comprehensive Cancer Center; 3Department of Epidemiology and Preventive Medicine, University of Maryland School of Medicine; and 4Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, Maryland.

OBJECTIVE: The purpose of this study was to evaluate whether genetic polymorphisms in selected cytochrome P450 enzymes (CYPc17{alpha}, CYP1A1, and CYP1B1), estradiol (E2) levels, and estrone levels were associated with hot flushes.

METHODS: Women with hot flushes were those aged 45–54 years who reported ever experiencing hot flushes (n = 354). Women without hot flushes were those aged 45–54 years who reported never experiencing hot flushes (n = 258). Each participant completed a questionnaire and provided a blood sample for determination of genotypes, E2 levels, and estrone levels.

RESULTS: Carriers of the CYP1B1 (Val432Leu) polymorphism were more likely to report having any hot flushes (risk ratio [RR] 1.16, 95% confidence interval (CI) 0.98–1.37) and at least weekly hot flushes (RR 1.29, 95% CI 0.98–1.70) than women without the polymorphism, although these associations were of borderline statistical significance. In addition, carriers of the CYP1B1 polymorphism were likely to have a statistically significant 30% increased risk of reporting moderate to severe hot flushes (RR 1.30, 95% CI 1.02–1.67) and a statistically significant 27% increased risk of reporting hot flushes lasting a year or more (RR 1.27, 95% CI 1.00–1.61) compared with women without the polymorphism. There were no associations between CYP1A1 or CYPc17{alpha} polymorphisms and hot flushes. Low E2 and estrone levels were associated with hot flushes, but they did not alter the association between the CYP1B1 polymorphism and hot flushes.

CONCLUSION: These data suggest that a CYP1B1 polymorphism may be associated with severe and persistent hot flushes, independent of E2 and estrone levels.

LEVEL OF EVIDENCE: III






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