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| Conference 2003 |  |
THE EFFECTS OF ANDROGENS ON THE VASCULAR SYSTEM Professor Jesper Mehlsen, Medical Director, Department of Clinical Physiology & Nuclear Medicine H:S Frederiksberg Hospital University of Copenhagen, Denmark. The reported frequency of symptomatic peripheral arterial disease is approximately
2% in middle-aged subjects, whereas "silent" ischaemia of the legs seems
to affect ten times as many. Peripheral atherosclerosis often takes on a benign
course with regard to the lower extremities, but the condition is associated with
a substantial increase in overall mortality, and particularly in cardiac and cerebrovascular
events. Testosterone has significant impact on many of the components involved
in the development of atherosclerosis and the covariation between age-related
reductions in testosterone and increments in the prevalence of peripheral vascular
disease may thus be more than a mere coincidence. Testosterone has been shown
to be reduced in men admitted to hospital for stroke or myocardial infarction
and to be significantly lower in men with coronary atherosclerosis when compared
to healthy age matched controls. In the early phase of atherosclerotic
disease, LDL-cholesterol delivers lipids to the arterial intima and especially
the lipoprotein(a) part has been strongly associated with the subsequent vascular
disease. Plasma concentrations of testosterone are inversely correlated to the
level of lipoprotein(a) and the hormone may thus have an anti-atherosclerotic
effect by lowering lipid deposition. The migration of monocytes in to the arterial
intima is an important step in the early phases of atherosclerosis especially
when combined with intra-intimal lipid oxidation. Testosterone seems to have beneficial
effects particularly on the latter process and possibly also on the ensuing auto-immune
response. Plaque rupture appears to be the causative factor in acute ischemic
events through platelet activation and fibrin deposition. Testosterone counteracts
this process by increasing the available amount of plasminogen and by reducing
the fibrinogen levels in plasma. Once atherosclerosis is established, testosterone injections increase
skeletal muscle blood flow in the lower extremities and dilates coronary arteries
– both effects most likely resulting from a direct interaction with the endothelium.
As a possible consequence of this, testosterone has been shown to increase the
ischaemia free period during exercise in men with coronary heart disease and also
to reduce the risk of restenosis after angioplastic interventions in animals. In 1995, an editorial in
Circulation concluded: “Perhaps it is timely for the human pharmacology
of anabolic steroids to emerge from the locker room and be subjected
to the objective scrutiny of clinical research.” On the basis of the literature
published since then there seems to be an even stronger case for continued studies
in to the clinical effects of testosterone in cardiovascular disease. Professor Jesper Mehlsen, MD, PhD. Medical Director, Department of Clinical Physiology & Nuclear Medicine H:S Frederiksberg Hospital University of Copenhagen, Denmark. E-mail: Jesper.Mehlsen@fh.hosp.dk President of the Danish Society of Clinical Physiology and Nuclear Medicine
(1996-99). Member of the board in the Danish Hypertension Society (1994-2000). Vice-president of the Danish Organisation of Laboratory Medicine (1995-98). Vice-president of the Danish Society for the Prevention of Circulatory
Disease (1996-). President of the Association of Chief Physicians at Frederiksberg Hospital
(1999- ). Author/co-author of 143 scientific papers. Presenter of 96 and co-author of 147 oral presentations/posters at International,
Nordic or National Scientific Meetings. Referee at four international scientific journals. Presently member of the International Steering Committee and Danish co-ordinator
for the Anglo-Scandinavian Clinical Outcomes Trial (ASCOT). Supervisor for PhD-students and medical students on scholarships President of the Danish Society of Clinical Physiology and Nuclear Medicine
(1996-99). Member of the board in the Danish Hypertension Society (1994-2000). Vice-president of the Danish Organisation of Laboratory Medicine (1995-98). Vice-president of the Danish Society for the Prevention of Circulatory
Disease (1996-). President of the Association of Chief Physicians at Frederiksberg Hospital (1999- ). | |