, Volume 58, Issue 1, pp 91–96 | Cite as

Sex hormones and the risk of atrial fibrillation: The Multi-Ethnic Study of Atherosclerosis (MESA)

  • Wesley T. O’NealEmail author
  • Saman Nazarian
  • Alvaro Alonso
  • Susan R. Heckbert
  • Viola Vaccarino
  • Elsayed Z. Soliman
Original Article



Atrial fibrillation is more prevalent in men than women. Due to these sex differences in atrial fibrillation susceptibility, we examined whether sex hormones have differing associations with atrial fibrillation risk in men and women.


This analysis included 4883 (mean age = 63 ± 10 years; 39% women; 64% non-white) participants from the Multi-Ethnic Study of Atherosclerosis. Sex hormones (total testosterone, bioavailable testosterone, estradiol, and sex hormone binding globulin) were measured at baseline (2000-2002) for all male and all postmenopausal female participants. Atrial fibrillation was ascertained by hospital discharge records, Medicare claims data, and study electrocardiograms through December 31, 2012.


Over a median follow-up of 10.9 years, a total of 613 (13%) atrial fibrillation cases were detected. A higher incidence rate of atrial fibrillation was observed for males (n = 385, age-standardized incidence rate per 1000 person-years = 12.3, 95%CI = 11.1, 13.6) than females (n = 228, age-standardized incidence rate per 1000 person-years = 9.0, 95%CI = 7.9, 10.3). In men, higher bioavailable testosterone levels were associated with increased atrial fibrillation risk (HR = 1.32, 95%CI = 1.01, 1.74; p = 0.044; comparing 3rd to 1st tertile), while an association in the opposite direction was observed for women (HR = 0.81, 95%CI = 0.58, 1.13; p = 0.22; comparing 3rd to 1st tertile). Other hormones were not associated with atrial fibrillation in men or women.


Higher levels of endogenous bioavailable testosterone contribute to atrial fibrillation development in men. The combination of endogenous bioavailable testosterone and other risk factors potentially are important for atrial fibrillation development in men.


Sex hormones Atrial fibrillation Epidemiology Risk 



The authors thank the other investigators, the staff, and the participants of the MESA study for their valuable contributions. A full list of participating MESA investigators and institutions can be found at


This research was supported by contracts N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, and N01-HC-95169 from the National Heart, Lung, and Blood Institute. This research was supported by grants UL1-TR-000040 and UL1-TR-001079 from the National Center for Research Resources, 16EIA26410001 from the American Heart Association, and R01-HL-127659 from the National Heart, Lung, and Blood Institute. W.T.O. is supported by the National Heart, Lung, And Blood Institute of the National Institutes of Health under Award Number F32-HL-134290. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Compliance with ethical standards

Conflict of interest

Dr. Nazarian is principal investigator for research funds awarded to Johns Hopkins University from Biosense Webster Inc and is also a consultant to Biosense Webster, St Jude Medical, CardioSolv, and Spectranetics. The other authors declare that they have no competing interests.

Ethical approval

All procedures in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Supplementary material

12020_2017_1385_MOESM1_ESM.docx (14 kb)
Supplementary Information


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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  1. 1.Department of Medicine, Division of CardiologyEmory University School of MedicineAtlantaUSA
  2. 2.Department of Medicine, Division of CardiologyUniversity of Pennsylvania School of MedicinePhiladelphiaUSA
  3. 3.Department of Epidemiology, Rollins School of Public HealthEmory UniversityAtlantaUSA
  4. 4.Cardiovascular Health Research UnitUniversity of WashingtonSeattleUSA
  5. 5.Department of EpidemiologyUniversity of WashingtonSeattleUSA
  6. 6.Department of Internal Medicine, Section on CardiologyWake Forest School of MedicineWinston-SalemUSA
  7. 7.Epidemiological Cardiology Research Center (EPICARE), Department of Epidemiology and PreventionWake Forest School of MedicineWinston-SalemUSA

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