Sex Hormones and Incident Heart Failure in Men and Postmenopausal Women: The Atherosclerosis Risk in Communities Study

J Clin Endocrinol Metab. 2020 Oct 1;105(10):e3798-e3807. doi: 10.1210/clinem/dgaa500.


Context: Sex differences exist in heart failure (HF) phenotypes, but there is limited research on the role of sex hormones in HF and its subtypes.

Objective: To examine the associations of total testosterone, dehydroepiandrosterone sulfate (DHEA-S), and sex hormone-binding globulin (SHBG) with incident HF, HF with preserved ejection fraction (HFpEF), and HF with reduced ejection fraction (HFrEF).

Design: Atherosclerosis Risk in Communities (ARIC) study (prospective cohort study). Median follow-up is 19.2 years.

Setting: General community.

Participants: 4107 men and 4839 postmenopausal women, with mean age of 63.2 (standard deviation [SD] 5.7) and 62.8 (5.5) years, respectively.

Exposure: Plasma sex hormone levels were measured at visit 4 (1996-1998).

Main outcome measures: Incident HF events were identified through hospital discharge codes and death certificates.

Results: The Hazard Ratios for HF associated with 1 SD decrease in log-transformed total testosterone, DHEA-S, and SHBG were 1.10 (95% confidence interval 1.03, 1.17), 1.07 (1.00, 1.15), and 1.04 (0.96, 1.11) in men, and 1.05 (0.99, 1.13), 1.17 (1.09, 1.24), and 0.93 (0.85, 1.01) in women, respectively. The associations between sex hormones with subtypes of HF had similar patterns but were attenuated and became statistically insignificant.

Conclusion: In this prospective cohort, lower levels of endogenous testosterone and DHEA-S in men and DHEA-S in postmenopausal women were associated with the development of HF. Similar directions of association in both sexes and both HF subtypes suggest that sex hormones play a role in the development of HF through common pathways regardless of sex.

Keywords: DHEA-S; HFpEF; HFrEF; SHBG; heart failure; sex hormone; testosterone.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Atherosclerosis / blood
  • Atherosclerosis / complications
  • Atherosclerosis / epidemiology*
  • Dehydroepiandrosterone Sulfate / blood*
  • Female
  • Follow-Up Studies
  • Heart Failure / blood
  • Heart Failure / epidemiology*
  • Heart Failure / etiology
  • Heart Failure / physiopathology
  • Humans
  • Male
  • Middle Aged
  • Postmenopause / blood
  • Prospective Studies
  • Sex Factors
  • Sex Hormone-Binding Globulin / analysis*
  • Stroke Volume / physiology
  • Testosterone / blood*


  • Sex Hormone-Binding Globulin
  • Testosterone
  • Dehydroepiandrosterone Sulfate