Metabolomic Effects of Hormone Therapy and Associations With Coronary Heart Disease Among Postmenopausal Women.
Aged
Animals
Clinical Trials as Topic
Coronary Disease
/ epidemiology
Estrogens, Conjugated (USP)
/ adverse effects
Female
Hormone Replacement Therapy
/ adverse effects
Horses
Humans
Incidence
Medroxyprogesterone Acetate
/ adverse effects
Metabolome
Metabolomics
Placebos
Postmenopause
/ drug effects
Risk Factors
Triglycerides
/ metabolism
Women's Health
cardiovascular disease
estrogens
heart disease
medroxyprogesterone acetate
metabolome
women
Journal
Circulation. Genomic and precision medicine
ISSN: 2574-8300
Titre abrégé: Circ Genom Precis Med
Pays: United States
ID NLM: 101714113
Informations de publication
Date de publication:
12 2020
12 2020
Historique:
pubmed:
4
11
2020
medline:
27
10
2021
entrez:
3
11
2020
Statut:
ppublish
Résumé
In the WHI-HT trials (Women's Health Initiative Hormone Therapy), treatment with oral conjugated equine estrogens and medroxyprogesterone acetate (CEE+MPA) resulted in increased risk of coronary heart disease (CHD), whereas oral conjugated equine estrogens (CEE) did not. Four hundred eighty-one metabolites were measured at baseline and at 1-year in 503 and 431 participants in the WHI CEE and CEE+MPA trials, respectively. The effects of randomized HT on the metabolite profiles at 1-year was evaluated in linear models adjusting for baseline metabolite levels, age, body mass index, race, incident CHD, prevalent hypertension, and diabetes. Metabolites with discordant effects by HT type were evaluated for association with incident CHD in 944 participants (472 CHD cases) in the WHI-OS (Women's Health Initiative Observational Study), with replication in an independent cohort of 980 men and women at high risk for cardiovascular disease. HT effects on the metabolome were profound; 62% of metabolites significantly changed with randomized CEE and 52% with CEE+MPA (false discovery rate-adjusted Randomized treatment with oral HT resulted in large metabolome shifts that generally favored CEE alone over CEE+MPA in term of CHD risk. Discordant metabolite effects between HT regimens may partially mediate the differences in CHD risk between the 2 WHI-HT trials.
Sections du résumé
BACKGROUND
In the WHI-HT trials (Women's Health Initiative Hormone Therapy), treatment with oral conjugated equine estrogens and medroxyprogesterone acetate (CEE+MPA) resulted in increased risk of coronary heart disease (CHD), whereas oral conjugated equine estrogens (CEE) did not.
METHODS
Four hundred eighty-one metabolites were measured at baseline and at 1-year in 503 and 431 participants in the WHI CEE and CEE+MPA trials, respectively. The effects of randomized HT on the metabolite profiles at 1-year was evaluated in linear models adjusting for baseline metabolite levels, age, body mass index, race, incident CHD, prevalent hypertension, and diabetes. Metabolites with discordant effects by HT type were evaluated for association with incident CHD in 944 participants (472 CHD cases) in the WHI-OS (Women's Health Initiative Observational Study), with replication in an independent cohort of 980 men and women at high risk for cardiovascular disease.
RESULTS
HT effects on the metabolome were profound; 62% of metabolites significantly changed with randomized CEE and 52% with CEE+MPA (false discovery rate-adjusted
CONCLUSIONS
Randomized treatment with oral HT resulted in large metabolome shifts that generally favored CEE alone over CEE+MPA in term of CHD risk. Discordant metabolite effects between HT regimens may partially mediate the differences in CHD risk between the 2 WHI-HT trials.
Identifiants
pubmed: 33141616
doi: 10.1161/CIRCGEN.119.002977
pmc: PMC8824616
mid: NIHMS1757273
doi:
Substances chimiques
Estrogens, Conjugated (USP)
0
Placebos
0
Triglycerides
0
Medroxyprogesterone Acetate
C2QI4IOI2G
Types de publication
Journal Article
Observational Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e002977Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK102896
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201600002C
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201600018C
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201300008C
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL118264
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK046200
Pays : United States
Organisme : NHLBI NIH HHS
ID : K01 HL135342
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201600003C
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201600004C
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201600001C
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL122241
Pays : United States
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