Review Androgen deficiency and atherosclerosis: The lipid link Abdulmaged M. Traish a, ⁎, Rami Abdou a , Kyriakos E. Kypreos b a Department of Biochemistry and Urology, Boston University School of Medicine, Boston, MA, USA b Department of Medicine, Pharmacology Unit, University of Patras Medical School, Panepistimioupolis, Rio, TK. 26500, Greece abstract article info Article history: Received 15 May 2009 Received in revised form 15 September 2009 Accepted 28 September 2009 Keywords: Testosterone Atherosclerosis Androgen deficiency Androgen therapy LDL HDL Cardiovascular Disease Dyslipidemia Metabolic syndrome The relationship between androgen deficiency and atherosclerosis is complex, poorly understood, and remains controversial. The aim of this review is to evaluate the data in the literature to determine if androgen deficiency modulates lipid profiles and contributes to atherosclerosis development or progression. Studies in animals and humans suggest that androgen deficiency is associated with increased triglycerides (TGs), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C). Although the effects of androgen deficiency on high-density lipoprotein cholesterol (HDL-C) remains controversial, recent data suggest that androgen therapy is associated with increased levels of HDL-C and may improve reverse cholesterol transport. Animal studies suggested that androgen deprivation adversely affect lipid profiles and this was reversed by androgen treatment. Furthermore, androgen treatment of hypogonadal men significantly improved lipid profiles. Emerging data indicate that androgens play an important role in lipid metabolism. Therefore androgens are critical in the prevention and progression of atherosclerosis. Androgen deficiency contributes to increased TGs, TC, LDL-C and reduced HDL-C while androgen treatment results in a favorable lipid profile, suggesting that androgens may provide a protective effect against the development and/or progression of atherosclerosis. © 2009 Elsevier Inc. All rights reserved. Contents 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 303 2. Dyslipidemia and the lipid and lipoprotein transport system . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 304 3. Epidemiology of androgens and atherosclerosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 304 4. Interrelationship between testosterone and atherosclerosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 306 5. Androgen deprivation therapy and cardiovascular disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 307 6. Androgens and atheroprotective HDL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 308 7. Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 309 Acknowledgement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 310 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 310 1. Introduction Ever since the pioneering work of Charles-Édouard Brown- Séquard in the late 1800s with an elixir of guinea pig and dog testicles, early observation of the ability of “testicular substances” to prolong life continues to be enigmatic more than 200 years later. Since isolation and chemical characterization of androgens in the 1930s, considerable progress has been made in understanding the physio- logical function of androgens in many tissues and organs. However, their role in atherosclerosis and associated complications of vascular disease remains poorly defined. Androgens play important roles in male sexual differentiation and maintenance of libido, in addition to regulating body composition, erythropoesis, and osteoporosis (Sha- hidi, 2001). Androgen deficiency is characterized by symptoms including loss of muscle mass and strength, increased visceral fat mass, reduced libido, erectile dysfunction, loss of sexual hair, increased osteoporosis, lethargy, lack of energy, and changes in mood. Recent reports have suggested that androgens may have a role in vascular health, and androgen deficiency may represent a significant risk factor for cardiovascular disease (Basaria and Dobs, Vascular Pharmacology 51 (2009) 303–313 ⁎ Corresponding author. Laboratories for Sexual Medicine, Institute for Sexual Medicine, Boston University School of Medicine, Center for Advanced Biomedical Research, 700 Albany Street, W607, Boston, MA 02118, USA. Tel.: +1 617 638 4578; fax: +1 617 638 5412. E-mail address: atraish@bu.edu (A.M. Traish). 1537-1891/$ – see front matter © 2009 Elsevier Inc. All rights reserved. doi:10.1016/j.vph.2009.09.003 Contents lists available at ScienceDirect Vascular Pharmacology journal homepage: www.elsevier.com/locate/vph