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.