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CLINICAL RESEARCH: PERIPHERAL ARTERIAL DISEASE

Low Serum Testosterone and High Serum Estradiol Associate With Lower Extremity Peripheral Arterial Disease in Elderly Men

The MrOS Study in Sweden

Åsa Tivesten, MD, PhD^_*,_*, Dan Mellström, MD, PhD, Hans Jutberger, MD, Björn Fagerberg, MD, PhD^_*, Bodil Lernfelt, MD, PhD, Eric Orwoll, MD, PhD, Magnus K. Karlsson, MD, PhD, Östen Ljunggren, MD, PhD^|| and Claes Ohlsson, MD, PhD

^_* The Wallenberg Laboratory for Cardiovascular Research, Göteborg University, Göteborg, Sweden
Center for Bone Research at the Sahlgrenska Academy, Institute of Medicine, Göteborg University, Göteborg, Sweden
Bone and Mineral Unit, Oregon Health and Sciences University, Portland, Oregon
Clinical and Molecular Osteoporosis Research Unit, Department of Clinical Sciences, Lund University, Department of Orthopaedics, Malmö University Hospital, Malmö, Sweden
^|| Department of Medical Sciences, University of Uppsala, Uppsala, Sweden.

Manuscript received January 25, 2007; revised manuscript received April 3, 2007, accepted April 9, 2007.

^_* Reprint requests and correspondence: Dr. Åsa Tivesten, Wallenberg Laboratory for Cardiovascular Research, Bruna Stråket 16, Sahlgrenska University Hospital, S-413 45 Göteborg, Sweden. (Email: asa.tivesten{at}medic.gu.se).

Objectives: This study sought to determine whether serum levels of testosterone and estradiol associate with lower extremity peripheral arterial disease (PAD) in a large population-based cohort of elderly men.

Background: Few studies have explored the relationship between serum sex steroids and lower extremity PAD in men.

Methods: The Swedish arm of the MrOS (Osteoporotic Fractures in Men) study (n = 3,014; average age 75.4 years) assessed ankle-brachial index (ABI) and defined lower extremity PAD as ABI <0.90. Radioimmunoassay measured serum levels of total testosterone, estradiol, and sex hormone-binding globulin, and we calculated free testosterone and free estradiol levels from the mass action equations.

Results: A linear regression model including age, current smoking, previous smoking, diabetes, hypertension, body mass index, free testosterone, and free estradiol showed that free testosterone independently and positively associates with ABI (p < 0.001), whereas free estradiol independently and negatively associates with ABI (p < 0.001). Logistic regression analyses showed that free testosterone in the lowest quartile (vs. quartiles 2 to 4; odds ratio [OR] 1.65, 95% confidence interval [CI] 1.22 to 2.23, p = 0.001) and free estradiol in the highest quartile (vs. quartiles 1 to 3; OR 1.45, 95% CI 1.09 to 1.94, p = 0.012) independently associate with lower extremity PAD.

Conclusions: This cross-sectional study shows for the first time that low serum testosterone and high serum estradiol levels associate with lower extremity PAD in elderly men. Future prospective and interventional studies are needed to establish possible causal relationships between sex steroids and the development of lower extremity PAD in men.

Abbreviations and Acronyms   ABI = ankle-brachial index   BMI = body mass index   CI = confidence interval   CV = coefficient of variation   IRMA = immunoradiometric assay   OR = odds ratio   PAD = peripheral arterial disease   RIA = radioimmunoassay   SHBG = sex hormone-binding globulin

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