Genetic polymorphisms, hormone levels, and hot flashes in midlife women.
OBJECTIVE
Hot flashes disrupt the lives of millions of women each year. Although hot flashes are a public health concern, little is known about risk factors that predispose women to hot flashes. Thus, the objective of this study was to examine whether sex steroid hormone levels and genetic polymorphisms in hormone biosynthesis and degradation enzymes are associated with the risk of hot flashes.


METHODS
In a cross-sectional study design, midlife women aged 45-54 years (n=639) were recruited from Baltimore and its surrounding counties. Participants completed a questionnaire and donated a blood sample for steroid hormone analysis and genotyping. The associations between genetic polymorphisms and hormone levels, as well as the associations between genetic polymorphisms, hormone levels, and hot flashes were examined using statistical models.


RESULTS
A polymorphism in CYP1B1 was associated with lower dehydroepiandrosterone-sulfate (DHEA-S) and progesterone levels, while a polymorphism in CYP19 (aromatase) was associated with higher testosterone and DHEA-S levels. Lower progesterone and sex hormone binding globulin levels, lower free estradiol index, and a higher ratio of total androgens to total estrogens were associated with the experiencing of hot flashes. A polymorphism in CYP1B1 and a polymorphism in 3betaHSD were both associated with hot flashes.


CONCLUSIONS
Some genetic polymorphisms may be associated with altered levels of hormones in midlife women. Further, selected genetic polymorphisms and altered hormone levels may be associated with the risk of hot flashes in midlife women.
Schilling
Chrissy
C
Department of Epidemiology and Preventive Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Gallicchio
Lisa
L
Miller
Susan R
SR
Langenberg
Patricia
P
Zacur
Howard
H
Flaws
Jodi A
JA
D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D003430:Cross-Sectional Studies; D065633:Cytochrome P-450 CYP1B1; D004247:DNA / Q000032:analysis; D017931:DNA Primers; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood; D005260:Female; D005838:Genotype; D012739:Gonadal Steroid Hormones / Q000097:blood; D019584:Hot Flashes / Q000097:blood / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008593:Menopause; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011374:Progesterone / Q000097:blood; D012720:Severity of Illness Index; D013739:Testosterone / Q000097:blood
D017931:DNA Primers; D012739:Gonadal Steroid Hormones; D013739:Testosterone; D011374:Progesterone; D019314:Dehydroepiandrosterone Sulfate; D004247:DNA; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1