The relationship between sex hormones, sex hormone binding globulin and peripheral artery disease in older persons

Atherosclerosis. 2012 Dec;225(2):469-74. doi: 10.1016/j.atherosclerosis.2012.09.014. Epub 2012 Oct 3.


Objective: The prevalence of peripheral artery disease (PAD) increases with aging and is higher in persons with metabolic syndrome and diabetes. PAD is associated with adverse outcomes, including frailty and disability. The protective effect of testosterone and sex hormone binding globulin (SHBG) for diabetes in men suggests that the biological activity of sex hormones may affect PAD, especially in older populations.

Methods: Nine hundred and twenty-one elderly subjects with data on SHBG, testosterone (T), estradiol (E2) were selected from InCHIANTI study. PAD was defined as an Ankle-Brachial Index (ABI) < 0.90. Logistic regression models adjusted for age (Model 1), age, BMI, insulin, interleukin-6, physical activity, smoking, chronic diseases including metabolic syndrome (Model 2), and a final model including also sex hormones (Model 3) were performed to test the relationship between SHBG, sex hormones and PAD.

Results: The mean age (±SD) of the 419 men and 502 women was 75.0 ± 6.8 years. Sixty two participants (41 men, 21 women) had ABI < 0.90. Men with PAD had SHBG levels lower than men without PAD (p = 0.03). SHBG was negatively and independently associated with PAD in men (p = 0.028) but not in women. The relationship was however attenuated after adjusting for sex hormones (p = 0.07). The E2 was not significantly associated with PAD in both men and women. In women, but not in men, T was positively associated with PAD, even after adjusting for multiple confounders, including E2 (p = 0.01).

Conclusions: Low SHBG and high T levels are significantly and independently associated with the presence of PAD in older men and women, respectively.

Publication types

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

MeSH terms

  • Age Factors
  • Aged
  • Aged, 80 and over
  • Aging / blood
  • Ankle Brachial Index
  • Biomarkers / blood
  • Chi-Square Distribution
  • Comorbidity
  • Cross-Sectional Studies
  • Down-Regulation
  • Estradiol / blood*
  • Female
  • Humans
  • Italy / epidemiology
  • Logistic Models
  • Male
  • Peripheral Arterial Disease / blood*
  • Peripheral Arterial Disease / diagnosis
  • Peripheral Arterial Disease / epidemiology
  • Risk Factors
  • Sex Factors
  • Sex Hormone-Binding Globulin / analysis*
  • Testosterone / blood*
  • Up-Regulation


  • Biomarkers
  • Sex Hormone-Binding Globulin
  • Testosterone
  • Estradiol