Low serum testosterone and high serum estradiol associate with lower extremity peripheral arterial disease in elderly men. The MrOS Study in Sweden.
OBJECTIVE
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.
Tivesten
Asa
A
The Wallenberg Laboratory for Cardiovascular Research, Göteborg University, Göteborg, Sweden. asa.tivesten@medic.gu.se
Mellström
Dan
D
Jutberger
Hans
H
Fagerberg
Björn
B
Lernfelt
Bodil
B
Orwoll
Eric
E
Karlsson
Magnus K
MK
Ljunggren
Osten
O
Ohlsson
Claes
C
D000368:Aged; D000369:Aged, 80 and over; D001794:Blood Pressure / Q000502:physiology; D001916:Brachial Artery / Q000503:physiopathology; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D004958:Estradiol / Q000097:blood*; D006801:Humans; D007866:Leg / Q000098:blood supply; D008297:Male; D016491:Peripheral Vascular Diseases / Q000097:blood* / Q000175:diagnosis / Q000503:physiopathology; D012720:Severity of Illness Index; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D013548:Sweden; D013739:Testosterone / Q000097:blood*