on May 16, 2002
Published online before print May 16, 2002, doi: 10.1161/01.ATV.0000022167.80130.A6
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Submitted on February 25, 2002
Accepted on April 19, 2002
Prospective Study of Effect of Androgens on Serum Inflammatory Markers in Men
Martin K.C. Ng ;
From the Department of Cardiology (M.K.C.N., D.S.C.), Royal Prince Alfred Hospital and Heart Research Institute; the Department of Andrology (P.Y.L., L.P.L., D.J.H.), Concord Hospital; ANZAC Research Institute (P.Y.L., D.J.H.); the Department of Clinical Immunology (A.J.W.), Royal Prince Alfred Hospital; the Heart Research Institute (S.N.); and the University of Sydney (D.J.H.), Sydney, Australia.
* To whom correspondence should be addressed. E-mail: davidc{at}card.rpa.cs.nsw.gov.au.
Objective—Because male sex is an independent risk factor for the severity of atherosclerosis, it is possible that androgens may be proatherogenic. There is evidence that sex hormones, particularly estrogens, regulate (or modulate) inflammation, a process integral to atherogenesis. Because levels of serum inflammatory markers predict cardiovascular outcomes, we prospectively assessed the effects of androgen therapy on these markers in older men.
Methods and Results—Levels of high-sensitivity C-reactive
protein (CRP), soluble intracellular adhesion molecule-1 (sICAM-1), and
soluble vascular cell adhesion molecule-1 (sVCAM-1) were measured from
sera collected at baseline and at the end of 2 randomized double-blind
placebo-controlled trials evaluating the effects of 3 months of
androgen treatment with either dihydrotestosterone (DHT) or recombinant
human chorionic gonadotropin (rhCG) in healthy men aged 
60
years with partial androgen deficiency (serum testosterone
levels <15 nmol/L). For the DHT study (70 mg transdermally daily), 33
men completed 3 months of treatment (16 men were treated with DHT, and
there were 17 controls). For the rhCG (250 µg twice weekly) study, 20
men were treated with rhCG, and there were 20 controls. In both
studies, groups were well matched for age and vascular risk factors.
Androgen levels (DHT and testosterone) were consistently
maintained at eugonadal levels throughout the trials, with estradiol
markedly increased by rhCG but not DHT. Baseline CRP levels were 0.74
to 1.49 mg/L, sVCAM-1 levels were 847 to 950 ng/mL, and sICAM-1 levels
were 256 to 292 ng/mL in all groups. Neither DHT nor rhCG resulted in
significant changes in CRP, sVCAM-1, or sICAM-1 compared with placebo
(P>0.3 in both
studies).
Conclusions—Exogenous androgen therapy with or without increased estradiol levels does not alter serum inflammatory markers in older men; this finding is in contrast to the effects of estrogens on inflammatory markers that have been found in postmenopausal women. These data provide a measure of reassurance concerning potential adverse cardiovascular effects of androgen therapy in older men.
Key words: inflammation • testosterone • estrogen • atherosclerosis
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