Objective: This study evaluated whether genes involved in the metabolism of steroid hormones are associated with hormone levels or menopausal symptoms.
Methods: We used a population-based prospective sample of 436 African American (AA) and European American (EA) women who were premenopausal at enrollment and were followed longitudinally through menopause. We evaluated the relationship between steroid hormone metabolism genotypes at COMT, CYP1A2, CYP1B1, CYP3A4, CYP19, SULT1A1, and SULT1E1 with hormone levels and menopausal features.
Results: In EA women, SULT1E1 variant carriers had lower levels of dehydroepiandrosterone sulfate, and SULT1A1 variant carriers had lower levels of estradiol, dehydroepiandrosterone sulfate, and testosterone compared with women who did not carry these variant alleles. In AA women, CYP1B1*3 genotypes were associated with hot flashes (odds ratio [OR], 0.62; 95% CI, 0.40-0.95). Interactions of CYP1A2 genotypes were associated with hot flashes across menopausal stage (P = 0.006). Interactions of CYP1B1*3 (P = 0.02) and CYP1B1*4 (P = 0.03) with menopausal stage were associated with depressive symptoms. In EA women, SULT1A1*3 was associated with depressive symptoms (OR, 0.53; 95% CI, 0.41-0.68) and hot flashes (OR, 2.08; 95% CI, 1.64-2.63). There were significant interactions between SULT1A1*3 and hot flashes (P < 0.001) and between SULT1A1*2 and depressive symptoms (P = 0.007) on menopausal stage, and there were race-specific effects of SULT1A1*2, SULT1A1*3, CYP1B1*3, and CYP3A4*1B on menopause.
Conclusions: Our results suggest that genotypes are associated with the occurrence of menopause-related symptoms or the timing of the menopausal transition.
In this study, whether genes involved in the metabolism of steroid hormones are associated with hormone levels or menopausal symptoms was evaluated. Results suggest that genotypes are associated with the occurrence of menopause-related symptoms or the timing of the menopausal transition.
From the 1Center for Clinical Epidemiology and Biostatistics, 2Abramson Cancer Center, and 3Department of Obstetrics and Gynecology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania.
Received January 23, 2010; revised and accepted February 16, 2010.
Dr. Su is now with the Department of Reproductive Medicine, University of California, San Diego, La Jolla, CA.
Funding/support: R01-AG-12745 (E.W.F.) and RR024134 (Clinical and Translational Research Center). K12HD001265 and ACS MRSG08110-01 (HIS).
Financial disclosure/conflicts of interest: None reported.
Address correspondence to: Timothy R. Rebbeck, PhD, Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, 217 Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104-6021. E-mail: firstname.lastname@example.org