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CLINICAL RESEARCH: ATHEROSCLEROSIS

Increased Carotid Atherosclerosis in Andropausal Middle-Aged Men

Juuso Mäkinen, MD^_*,, Mikko J. Järvisalo, MD, PhD^_*,,,, Pasi Pöllänen, MD, PhD^,||, Antti Perheentupa, MD, PhD^,#, Kerttu Irjala, MD, PhD^¶, Markku Koskenvuo, MD, PhD^_**, Juha Mäkinen, MD, PhD, Ilpo Huhtaniemi, MD, PhD^#, and Olli T. Raitakari, MD, PhD^,,_*

^_* Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland
Department of Clinical Physiology, University of Turku, Turku, Finland
PET Centre, University of Turku, Turku, Finland
Department of Gynecology and Obstetrics, University of Turku, Turku, Finland
^|| Department of Anatomy, University of Turku, Turku, Finland
^¶ Department of Clinical Chemistry, University of Turku, Turku, Finland
^# Department of Physiology, University of Turku, Turku, Finland
^_** Department of Public Health, University of Turku, Turku, Finland
Department of Internal Medicine, Satakunta Central Hospital, Pori, Finland
Institute of Reproductive and Developmental Biology, Hammersmith Campus, Imperial College London, London, United Kingdom

Manuscript received August 26, 2004; revised manuscript received December 22, 2004, accepted January 11, 2005.

^_* Reprint requests and correspondence: Dr. Olli T. Raitakari, Turku PET Centre, Kiinamyllynkatu 4-8, FIN-20500 Turku, Finland (Email: olli.raitakari{at}utu.fi).

OBJECTIVES: This study examined the association between carotid artery intima-media thickness (IMT), serum sex hormone levels, and andropausal symptoms in middle-aged men.

BACKGROUND: Male sex hormones may play a dual role in the pathogenesis of atherosclerosis in men by carrying both proatherogenic and atheroprotective effects.

METHODS: We studied 239 40- to 70-year-old men (mean ± SD: 57 ± 8 years) who participated in the Turku Aging Male Study and underwent serum lipid and sex hormone measurements. Ninety-nine men (age 58 ± 7 years) were considered andropausal (i.e., serum testosterone <9.8 nmol/l or luteinizing hormone [LH] >6.0 U/l and testosterone in the normal range), and in both situations, they had subjective symptoms of andropause (a high symptom score in questionnaire). Three were excluded because of diabetes. The rest of the men (age 57 ± 8 years) served as controls. Carotid IMT was determined using high-resolution B-mode ultrasound, and serum testosterone, estradiol (E₂), LH, and sex hormone-binding globulin were measured using standard immunoassays.

RESULTS: Andropausal men had a higher maximal IMT compared with controls in the common carotid (1.08 ± 0.34 vs. 1.00 ± 0.23, p < 0.05) and in the carotid bulb (1.44 ± 0.48 vs. 1.27 ± 0.35, p = 0.003). Common carotid IMT correlated inversely with serum testosterone (p = 0.003) and directly with LH (p = 0.006) in multivariate models adjusted for age, total cholesterol, body mass index, blood pressure, and smoking.

CONCLUSIONS: Middle-aged men with symptoms of andropause, together with absolute or compensated (as reflected by high normal to elevated LH) testosterone deficiency, show increased carotid IMT. These data suggest that normal testosterone levels may offer protection against the development of atherosclerosis in middle-aged men.

Abbreviations and Acronyms   AMS = Aging Male Symptoms Questionnaire   CHD = coronary heart disease   CV = coefficient of variation   E2 = estradiol   HbA1c = glycated hemoglobin   IMT = intima-media thickness   LDL = low-density lipoprotein   LH = luteinizing hormone   T3Q = Turku 3-Query

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