Influence of SULT1A1 genetic variation on age at menopause, estrogen levels, and response to hormone therapy in recently postmenopausal white women

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Abstract

Objective: Onset and symptoms of menopause, and response to hormone therapy (HT) show large interindividual variability. SULT1A1 encodes for a highly expressed enzyme that metabolizes estrogens. We evaluated the relationship between genetic variation in SULT1A1, menopause age, symptoms, and response to HT. Methods: Women enrolled in the Kronos Early Estrogen Prevention Study at Mayo Clinic were randomized to 48 months of treatment with oral conjugated equine estrogen (n=34), transdermal 17β-estradiol (E2) (n=33), or placebo (n=35). Linear regression models and ANOVA were used to test for association of SULT1A1 copy number, rs3760091, rs750155, and rs9282861 (SULT1A1-2), with age at menopause and symptoms, levels of estrogens (estrone [E1], estrone sulfate [E1S], E2, and estradiol sulfate [E2S]), before and after HT. Results: SULT1A1 gene copy number affected the minor allele frequency for each single nucleotide polymorphisms tested. Before administration of exogenous hormones, increasing number of G alleles at rs9282861 was associated with earlier age at menopause (P=0.014), lower frequency of night sweats (P=0.009), and less severe insomnia (P=0.046). After 48 months of treatment, SULT1A1 genotype was not associated with the presence of menopausal symptoms. In women randomized to oral conjugated equine estrogen, increasing number of the A allele at rs750155 was associated with lower E1S and E2S (P=0.004 and 0.017), whereas increasing number of the C allele at rs3760091 was associated with lower E2S/ E2 (P=0.044). Conclusions: Interindividual variability in onset of menopause and symptoms before initiation of HT is explained in part by genetic variation in SULT1A1 and may represent a step toward individualizing HT treatment decisions.

Original languageEnglish (US)
Pages (from-to)863-869
Number of pages7
JournalMenopause
Volume23
Issue number8
DOIs
StatePublished - Jul 26 2016

Fingerprint

Menopause
Estrogens
Hormones
Conjugated (USP) Estrogens
Alleles
Therapeutics
Linear Models
Gene Dosage
Sweat
Estrone
Sleep Initiation and Maintenance Disorders
Gene Frequency
Single Nucleotide Polymorphism
Estradiol
Analysis of Variance
Genotype
Placebos
Enzymes
estradiol sulfate

Keywords

  • 17β-estradiol
  • Conjugated equine estrogens
  • Kronos Early Estrogen Prevention Study

ASJC Scopus subject areas

  • Obstetrics and Gynecology

Cite this

@article{efb84e8ed87f464eba6e381c23f051d2,
title = "Influence of SULT1A1 genetic variation on age at menopause, estrogen levels, and response to hormone therapy in recently postmenopausal white women",
abstract = "Objective: Onset and symptoms of menopause, and response to hormone therapy (HT) show large interindividual variability. SULT1A1 encodes for a highly expressed enzyme that metabolizes estrogens. We evaluated the relationship between genetic variation in SULT1A1, menopause age, symptoms, and response to HT. Methods: Women enrolled in the Kronos Early Estrogen Prevention Study at Mayo Clinic were randomized to 48 months of treatment with oral conjugated equine estrogen (n=34), transdermal 17β-estradiol (E2) (n=33), or placebo (n=35). Linear regression models and ANOVA were used to test for association of SULT1A1 copy number, rs3760091, rs750155, and rs9282861 (SULT1A1-2), with age at menopause and symptoms, levels of estrogens (estrone [E1], estrone sulfate [E1S], E2, and estradiol sulfate [E2S]), before and after HT. Results: SULT1A1 gene copy number affected the minor allele frequency for each single nucleotide polymorphisms tested. Before administration of exogenous hormones, increasing number of G alleles at rs9282861 was associated with earlier age at menopause (P=0.014), lower frequency of night sweats (P=0.009), and less severe insomnia (P=0.046). After 48 months of treatment, SULT1A1 genotype was not associated with the presence of menopausal symptoms. In women randomized to oral conjugated equine estrogen, increasing number of the A allele at rs750155 was associated with lower E1S and E2S (P=0.004 and 0.017), whereas increasing number of the C allele at rs3760091 was associated with lower E2S/ E2 (P=0.044). Conclusions: Interindividual variability in onset of menopause and symptoms before initiation of HT is explained in part by genetic variation in SULT1A1 and may represent a step toward individualizing HT treatment decisions.",
keywords = "17β-estradiol, Conjugated equine estrogens, Kronos Early Estrogen Prevention Study",
author = "Ann Moyer and {De Andrade}, Mariza and Weinshilboum, {Richard M} and Miller, {Virginia M}",
year = "2016",
month = "7",
day = "26",
doi = "10.1097/GME.0000000000000648",
language = "English (US)",
volume = "23",
pages = "863--869",
journal = "Menopause",
issn = "1072-3714",
publisher = "Lippincott Williams and Wilkins",
number = "8",

}

TY - JOUR

T1 - Influence of SULT1A1 genetic variation on age at menopause, estrogen levels, and response to hormone therapy in recently postmenopausal white women

AU - Moyer, Ann

AU - De Andrade, Mariza

AU - Weinshilboum, Richard M

AU - Miller, Virginia M

PY - 2016/7/26

Y1 - 2016/7/26

N2 - Objective: Onset and symptoms of menopause, and response to hormone therapy (HT) show large interindividual variability. SULT1A1 encodes for a highly expressed enzyme that metabolizes estrogens. We evaluated the relationship between genetic variation in SULT1A1, menopause age, symptoms, and response to HT. Methods: Women enrolled in the Kronos Early Estrogen Prevention Study at Mayo Clinic were randomized to 48 months of treatment with oral conjugated equine estrogen (n=34), transdermal 17β-estradiol (E2) (n=33), or placebo (n=35). Linear regression models and ANOVA were used to test for association of SULT1A1 copy number, rs3760091, rs750155, and rs9282861 (SULT1A1-2), with age at menopause and symptoms, levels of estrogens (estrone [E1], estrone sulfate [E1S], E2, and estradiol sulfate [E2S]), before and after HT. Results: SULT1A1 gene copy number affected the minor allele frequency for each single nucleotide polymorphisms tested. Before administration of exogenous hormones, increasing number of G alleles at rs9282861 was associated with earlier age at menopause (P=0.014), lower frequency of night sweats (P=0.009), and less severe insomnia (P=0.046). After 48 months of treatment, SULT1A1 genotype was not associated with the presence of menopausal symptoms. In women randomized to oral conjugated equine estrogen, increasing number of the A allele at rs750155 was associated with lower E1S and E2S (P=0.004 and 0.017), whereas increasing number of the C allele at rs3760091 was associated with lower E2S/ E2 (P=0.044). Conclusions: Interindividual variability in onset of menopause and symptoms before initiation of HT is explained in part by genetic variation in SULT1A1 and may represent a step toward individualizing HT treatment decisions.

AB - Objective: Onset and symptoms of menopause, and response to hormone therapy (HT) show large interindividual variability. SULT1A1 encodes for a highly expressed enzyme that metabolizes estrogens. We evaluated the relationship between genetic variation in SULT1A1, menopause age, symptoms, and response to HT. Methods: Women enrolled in the Kronos Early Estrogen Prevention Study at Mayo Clinic were randomized to 48 months of treatment with oral conjugated equine estrogen (n=34), transdermal 17β-estradiol (E2) (n=33), or placebo (n=35). Linear regression models and ANOVA were used to test for association of SULT1A1 copy number, rs3760091, rs750155, and rs9282861 (SULT1A1-2), with age at menopause and symptoms, levels of estrogens (estrone [E1], estrone sulfate [E1S], E2, and estradiol sulfate [E2S]), before and after HT. Results: SULT1A1 gene copy number affected the minor allele frequency for each single nucleotide polymorphisms tested. Before administration of exogenous hormones, increasing number of G alleles at rs9282861 was associated with earlier age at menopause (P=0.014), lower frequency of night sweats (P=0.009), and less severe insomnia (P=0.046). After 48 months of treatment, SULT1A1 genotype was not associated with the presence of menopausal symptoms. In women randomized to oral conjugated equine estrogen, increasing number of the A allele at rs750155 was associated with lower E1S and E2S (P=0.004 and 0.017), whereas increasing number of the C allele at rs3760091 was associated with lower E2S/ E2 (P=0.044). Conclusions: Interindividual variability in onset of menopause and symptoms before initiation of HT is explained in part by genetic variation in SULT1A1 and may represent a step toward individualizing HT treatment decisions.

KW - 17β-estradiol

KW - Conjugated equine estrogens

KW - Kronos Early Estrogen Prevention Study

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