Associations of cortisol/testosterone and cortisol/sex hormone-binding globulin ratios with atherosclerosis in middle-age women

Ju Mi Lee, Laura A. Colangelo, Joseph E. Schwartz, Yuichiro Yano, David S. Siscovick, Teresa Seeman, Pamela J. Schreiner, Kiang J. Liu, Donald M. Lloyd-Jones, Philip Greenland

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Background and aims: The cortisol/testosterone (C/T) ratio has been hypothesized to be a better predictor of atherosclerosis than cortisol alone. No study has assessed whether the C/T and C/sex hormone-binding globulin (SHBG) ratios are associated with atherosclerosis in a U.S. population sample. Methods: This substudy included 367 women who had both cortisol from year 15 and testosterone and SHBG at year 16 of the Coronary Artery Risk Development in Young Adults study, an ongoing observational cohort in the United States. Of these, intima-media thickness (IMT) was available at follow-up year 20 in 339 (n = 332 with measurement at carotid bulb), and 303 were free of prevalent coronary artery calcium (CAC) at year 15. Area under the curve (AUC) of salivary cortisol was available in 302 individuals. Ratios of AUCs of cortisol to total testosterone, free testosterone, and SHBG were categorized into tertiles. Associations with CAC and IMT were assessed by regression models adjusted for age, race, body mass index, systolic blood pressure, menopause, oral contraceptive use, diabetes, alcohol, and smoking. Results: Only the highest tertile of the AUC/free testosterone ratio was positively associated with carotid bulb IMT (β = 0.088, P = 0.006). This tertile was also positively associated with new onset CAC between year 15 and 25 (OR 3.45, 95% CI 1.18–10.06). Tertiles of cortisol or testosterone alone were not associated with new onset CAC. Conclusion: AUC/Free testosterone ratio may be more associated with atherosclerosis in women than either indicator alone. The ratio may serve as a suitable biomarker of cortisol-linked stress.

Original languageEnglish (US)
Pages (from-to)203-209
Number of pages7
StatePublished - May 2016

Bibliographical note

Funding Information:
The Coronary Artery Risk Development in Young Adults (CARDIA) Study is conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with the University of Alabama at Birmingham ( HHSN268201300025C & HHSN268201300026C ), Northwestern University ( HHSN268201300027C ), University of Minnesota ( HHSN268201300028C ), Kaiser Foundation Research Institute ( HHSN268201300029C ), and Johns Hopkins University School of Medicine ( HHSN268200900041C ). CARDIA is also partially supported by the Intramural Research Program of the National Institute on Aging (NIA) and an intra-agency agreement between the NIA and NHLBI (AG0005). This manuscript has been reviewed by CARDIA for scientific content. The CWS was supported by the National Heart, Lung, and Blood Institute grant R01-HL065611 and contracts N01-HC-48047, N01-HC-48048, N01-HC-48049, and N01-HC-48050.

Funding Information:
JM Lee thanks the All But Dissertation (ABD) trainee program, which is supported by a National Research Foundation of Korea Grant funded by the Korean Government , for covering U.S. boarding costs while this research was carried out.


  • Atherosclerosis
  • Hormones
  • Stress

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