Presented at the 2012 AAPM Annual Meeting « Back

Hypogonadism in Men Using Daily Opioid Therapy for Chronic Noncancer Pain is Associated with Duration of Action of Opioid

Andrea L. Rubinstein, MD, andrea.l.rubinstein@kp.org¹, Diane M. Carpenter, MPH², Jerome Minkoff, MD¹, (1) Kaiser Permanente, Santa Rosa, California, (2) Oakland, California

Introduction: Since the 1970s opioid use has been linked to hypogonadism in men. To date, no one has evaluated whether the risk of hypogonadism is linked to specific opioids, duration of action, or total daily opioid dose. Methods: Upon the Kaiser Permanente investigational review board we examined 81 men between 18 and 80 between January 2009 and June 2010. All men were on stable dose of an opioid used daily for at least three months and none of them had previous diagnosis of hypogonadism. Total AM testosterone was drawn. Results: Subject characteristics are described in Table 1. Opioid regimens by duration of action and percentage of hypogonadal patients by opioid regimens are described in Table 2. Of men on long-acting opioids, 34/46 (74%) were hypogonadal. Of men on short-acting opioids, 12/43 (34%) were hypogonadal. This difference was statistically significant at p<0.001. The association of duration of action with hypogonadism while controlling for Morphine Sulfate Equivalent (MSE) dosage and BMI was evaluated using logistic regression. The multivariate analysis results are shown in Table 4. When controlling for dosage and BMI, patients on a long-acting opioids had 4.78 times greater odds of becoming hypogonadal than did patients on a short-acting opioids (95% confidence interval 1.51-15.07, p = 0.008). In the multivariate analysis, dose wasn’t significantly associated with hypogonadism. Conclusions: This is the first study to show that daily use of long-acting opioids increases the risk of hypogonadism in men when compared to daily use of short acting opioids. References: 1)Katz N; Mazer NA. The Impact of Opioids on the Endocrine System . Clin J Pain 2009; 25: 170-17. 2)Daniell HW Hypogonadism in men consuming sustained-action oral opioids J Pain 2002; 3 (5) 337-384. 3)Mendelson JH, Mendelson JE, Patch VD Plasma testosterone levels in heroin addiction and during methadone maintenance. J Pharmacol Exp Ther 1975; 192 (1): 211-17. 4)Cicero TJ, Bell RD, Wiest WG;, et.al. Function of male sex organs in heroin and methadone users NEJM 1975; 292 (17): 882-887 5)Aloisi AM, Aurilio C, Bachiocco V et al. Endocrine consequences of opioid therapy. Psychoneuroendocrinology 2009; 34 Suppl 1: S162-8. 6)Pereira J, Lawlor P, Vigano A et. al. Equianalgesic dose ratios for opioids. a critical review and proposals for long-term dosing. J Pain Symptom Manage 2001; 22 (2): 672-87. 7)Bhasin S, Cunningham GR, Hayes FJ et. al Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2010; 95(6): 2536-59. 8)Azizi F, Vagenakis AG, Longcope C, et. al. Decreased serum testosterone concentration in male heroin and methadone addicts. Steroids 1973; 22 (4): 467-72.

Funding: Funding for this study was provided by the Kaiser Permanente Northern California Community Benefits Program.