Re: Low serum testosterone in men is inversely associated with non-fasting serum triglycerides: The Tromsø study

Journal of the American College of Cardiology
Volume 50, Issue 11, 11 September 2007, Pages 1070-1076

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†
†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
The Wallenberg Laboratory for Cardiovascular Research, Göteborg
University, Göteborg, Sweden
Department of Medical Sciences, University of Uppsala, Uppsala,
Sweden.
§Clinical and Molecular Osteoporosis Research Unit, Department of
Clinical Sciences, Lund University, Department of Orthopaedics, Malmö
University Hospital, Malmö, Sweden

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.

This work was financially supported by grants from the Swedish Heart
and Lung Foundation, the Swedish Research Council, the Novo Nordisk
Foundation, the Tore Nilson Foundation, the Emelle Foundation, the
Göteborg Medical Society, the ALF/LUA research grant in Göteborg, and
the Swedish Medical Society.
Reprint requests and correspondence: Dr. Åsa Tivesten, Wallenberg
Laboratory for Cardiovascular Research, Bruna Stråket 16, Sahlgrenska
University Hospital, S-413 45 Göteborg, Sweden.



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