Effect of hormone metabolism genotypes on steroid hormone levels and menopausal symptoms in a prospective population-based cohort of women experiencing the menopausal transition.
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.
Rebbeck
Timothy R
TR
Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6021, USA. rebbeck@mail.med.upenn.edu
Su
H Irene
HI
Sammel
Mary D
MD
Lin
Hui
H
Tran
Teo V
TV
Gracia
Clarisa R
CR
Freeman
Ellen W
EW
D000328:Adult; D001741:Black or African American / Q000235:genetics; D015239:Arylsulfotransferase / Q000235:genetics; D002394:Catechol O-Methyltransferase / Q000235:genetics; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D003863:Depression / Q000235:genetics*; D005260:Female; D012739:Gonadal Steroid Hormones / Q000235:genetics; D019584:Hot Flashes / Q000235:genetics*; D006801:Humans; D008137:Longitudinal Studies; D008875:Middle Aged; D047648:Perimenopause / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D015238:Sulfotransferases / Q000235:genetics; D044465:White People / Q000235:genetics
D012739:Gonadal Steroid Hormones; D003577:Cytochrome P-450 Enzyme System; D002394:Catechol O-Methyltransferase; D015238:Sulfotransferases; D015239:Arylsulfotransferase; C117544:SULT1A1 protein, human; C020122:estrone sulfotransferase