Association of estrogen-related polymorphisms with age at menarche, age at final menstrual period, and stages of the menopausal transition.
OBJECTIVE
To explore the association of estrogen-related polymorphisms with age at menarche, age at onset and duration of stages of the menopausal transition, and age at final menstrual period (FMP).


METHODS
A total of 152 white women were genotyped for CYP17, CYP19 3-untranslated region, CYP19 TTTA7-13, HSDB1, CYP1A1, CYP1B1, and ESR1 polymorphisms. Analysis of variance was used to test a nonspecific model for differences among genotypes associated with each polymorphism.


RESULTS
Five of the 84 associations tested were significant at P < 0.05, which could be expected by chance. Women with two CYP19 7r alleles had menarche earlier (11.5 y) than those with one 7r allele (13.1 y). Women with two 11r alleles were 2 years older at onset of late stage than those with one 11r allele (50.7 y vs 48.6 y). Those with two 7r(-3) alleles were 2 years older at FMP than those without this allele (53.9 y vs 51.3 y). Women with the homozygous wild-type allele for HSDB1 (rs2830) were younger at FMP by 2 years than those with the heterozygous allele (50.8 y vs 52.9 y). Women with the heterozygous allele for CYP1B1*2 had a later age at menarche compared with women with the homozygous wild type (13 y vs 12.5 y).


CONCLUSIONS
Age at onset of late stage and FMP and age at menarche are associated with specific genetic polymorphisms in the estrogen biosynthesis and metabolism genes. However, because of the number of comparisons, these associations may be false positives. These findings should be confirmed with a larger sample of white women.
Mitchell
Ellen S
ES
Department of Family and Child Nursing, University of Washington, Seattle, WA 98195-7262, USA. nellem@u.washington.edu
Farin
Frederico M
FM
Stapleton
Patricia L
PL
Tsai
Jesse M
JM
Tao
Eunice Yun
EY
Smith-DiJulio
Kathleen
K
Woods
Nancy F
NF
D000328:Adult; D000367:Age Factors; D000483:Alleles; D001141:Aromatase / Q000235:genetics; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D065633:Cytochrome P-450 CYP1B1; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008572:Menarche / Q000235:genetics* / Q000378:metabolism; D008593:Menopause / Q000235:genetics* / Q000378:metabolism; D008597:Menstrual Cycle / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011960:Receptors, Estrogen / Q000235:genetics* / Q000378:metabolism; D018709:Statistics, Nonparametric; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics
D011960:Receptors, Estrogen; D003577:Cytochrome P-450 Enzyme System; D001141:Aromatase; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1; D013254:Steroid 17-alpha-Hydroxylase