title: Polymorphisms in the estrogen synthesis and metabolism pathways and symptoms during the menopausal transition: observations from the Seattle Midlife Women's Health Study.
abstract: OBJECTIVE
  The purpose of this study was to determine whether polymorphisms in the estrogen synthesis and metabolism pathways are associated with women's vasomotor symptom experiences during the menopausal transition.
  
  
  METHODS
  In 2002, a subset of women enrolled in the Seattle Midlife Women's Health Study since 1990 (N = 174) provided a buccal smear for genotyping. Women were recruited by complete ascertainment of selected multiethnic neighborhoods in 1990. Participants were midlife women with a mean age of 53 years in 2005, well educated, employed, married, and represented a multiethnic population. Genotyping was done for the following polymorphisms: CYP1A1m2; CYP1B1*2 and CYP1B1*3; CYP17 5'UTR; CYP19 3'UTR; CYP19 (TTTA)n; including CYP19 7r and CYP19 7(r-3); CYP19 8r and CYP19 11r; and ESR1PvuII and ESR1XbaI. Women rated their vasomotor symptom severity in diaries on days 5, 6, and 7 of the menstrual cycle or on a constant date each month for women skipping periods. Menopausal transition stage was determined from daily menstrual calendars. First voided urine specimens provided several times each year were assayed for estrone glucuronide.
  
  
  RESULTS
  Women with the CYP19 11r polymorphism reported more severe and frequent hot flashes during the middle and late menopausal transition stages and postmenopause and higher E1G levels during middle and late stages. None of the other polymorphisms studied were related to hot flashes or to estrone glucuronide levels.
  
  
  CONCLUSIONS
  These findings suggest a possible role for CYP19 polymorphisms in estrogen levels and in vasomotor symptoms during the menopausal transition that warrants further study in larger and more diverse populations of women.
authors.affiliation: Department of Family and Child Nursing, School of Nursing, University of Washington, Seattle, WA 98195-7260, USA. nfwoods@u.washington.edu
authors.forename: Nancy F
authors.initials: NF
authors.lastname: Woods
authors.forename: Ellen Sullivan
authors.initials: ES
authors.lastname: Mitchell
authors.forename: Yun
authors.initials: Y
authors.lastname: Tao
authors.forename: Hannah-Malia A
authors.initials: HM
authors.lastname: Viernes
authors.forename: Patricia L
authors.initials: PL
authors.lastname: Stapleton
authors.forename: Federico M
authors.initials: FM
authors.lastname: Farin
mesh_terms: D000483:Alleles; D001141:Aromatase / Q000235:genetics*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D015992:Body Mass Index; D003404:Creatinine / Q000652:urine; D047628:Estrogen Receptor alpha / Q000235:genetics; D004967:Estrogens / Q000096:biosynthesis / Q000378:metabolism*; D004970:Estrone / Q000031:analogs & derivatives / Q000652:urine; D005260:Female; D005838:Genotype; D019584:Hot Flashes / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008593:Menopause / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D011110:Polymorphism, Genetic; D018709:Statistics, Nonparametric; D014666:Vasomotor System / Q000502:physiology
chemical_list: D047628:Estrogen Receptor alpha; D004967:Estrogens; C015856:estrone-3-glucuronide; D004970:Estrone; D003404:Creatinine; D001141:Aromatase; D001189:Aryl Hydrocarbon Hydroxylases