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How does testosterone therapy affect cardiovascular risk?
Response by Ridwan Shabsigh, MD, Posted 07/05/07

It has long been suspected that androgens play a role in coronary artery disease (CAD) in men, but until recently, any relationship was anecdotal. New evidence strengthens the link between abnormally low androgen levels and cardiovascular disease (CVD).1-3

Hypogonadism is associated with central obesity, insulin resistance, low levels of high-density lipoprotein (HDL), and high levels of triglycerides (TG), fibrinogen, and plasminogen activator inhibitor-1 (PAI-1).1,4 Two recently published studies found significantly lower testosterone (T) levels in men with documented CAD than in control groups.2,3 Turhan et al showed that a free testosterone (FT) level <17.3 pg/mL was an independent risk factor for premature CAD (P =.026; odds ratio 3.3; 95% confidence interval 1.57-6.87) in men younger than 45 years (mean, 41 years).2 A weak but statistically significant positive correlation (r= 0.26, P =.004) between FT levels and total cholesterol was found, but no significant correlation between FT and low-density lipoprotein, HDL, or TG levels was detected.2 A similar study found an independent correlation between decreasing T levels and increasing severity of CAD (r =-0.52; P <.01).3 Thus, the physiological effects of T support a role for endogenous T in preventing atheroma and CVD.2,3

For men with hypogonadism, T therapy may provide some cardiovascular benefits, including improved insulin sensitivity and reduced serum levels of PAI-1, fibrinogen, body mass index, and visceral fat.1,4 Studies have shown no consistent effect on cholesterol.1,5 A recent randomized, double-blind, placebo-controlled trial of T therapy in 24 men older than 30 years with type 2 diabetes reported reduced central obesity, as measured by waist circumference (P =.03) and waist:hip ratio (P =.01), and improved insulin sensitivity, as measured by the homeostatic model index (HOMA), in the 14 men taking oral hypoglycemic agents (P =.02), which resulted in lower glycosylated hemoglobin (A1C; 3%) levels.6 For the 10 patients taking insulin, 5 patients receiving T therapy reduced daily insulin dosages by 7 ± 1.9 U.

T therapy is generally safe for men with CVD and hypogonadism.1 A meta-analysis of 30 trials (N=1,642, with 808 receiving T therapy) reported small and clinically negligible effects of T therapy on lipid fractions and blood pressure.5 Investigators have concluded that the cardiovascular effects of T therapy may be considered neutral to beneficial.1 Large randomized trials are needed.1,5 Caution should be exercised when prescribing T therapy for patients with congestive heart failure because of the potential for edema and increased hematocrit levels.1,7-9 Using such caution will help ensure safe and efficacious T therapy for men with hypogonadism.

 

References

  1. Shabsigh R, Katz M, Yan G, Makhsida N. Cardiovascular issues in hypogonadism and testosterone therapy. Am J Cardiol. 2005;96(suppl):67M-72M.
  2. Turhan S, Tulunay C, Gülec S, et al. The association between androgen levels and premature coronary artery disease in men. Coron Artery Dis. 2007;18:159-162.
  3. Rosano GMC, Sheiban I, Massaro R, et al. Low testosterone levels are associated with coronary artery disease in male patients with angina. Int J Impot Res. 2007;19:176-182.
  4. Jones RD, Nettleship JE, Kapoor D, Jones HT, Channer KS. Testosterone and atherosclerosis in aging men: purported association and clinical implications. Am J Cardiovasc Drugs. 2005;5:141-154.
  5. Haddad RM, Kennedy CC, Caples SM, et al. Testosterone and cardiovascular risk in men: a systematic review and meta-analysis of randomized placebo-controlled trials. Mayo Clin Proc. 2007;82:29-39.
  6. Kapoor D, Goodwin E, Channer KS, Jones TH. Testosterone replacement therapy improves insulin resistance, glycaemic control, visceral adiposity and hypercholesterolaemia in hypogonadal men with type 2 diabetes. Eur J Endocrinol. 2006;154:899-906.
  7. AndroGel [package insert]. Marietta, Ga: Unimed Pharmaceuticals, Inc.; 2004.
  8. Depo [package insert]. Kalamazoo, Mich: Pharmacia & Upjohn Company; 2002.
  9. Testim [package insert]. Malvern, Pa: Auxilium Pharmaceuticals, Inc.; 2003.

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