Oral Opioids for Chronic Non-cancer Pain: Higher Prevalence of Hypogonadism in Men than in Women

Abstract

The effect of chronic oral opioids on hypothalamus-pituitary-gonadal axis in women, and on bone mineral density (BMD) in men and women is not known. The objective of this cross-sectional study was to determine the effect of long-term oral opioids on gonadal status and BMD in male and female patients with chronic non-cancer pain (CNCP). We included 26 community-dwelling CNCP patients, 12 men and 14 premenopausal women, treated with oral opioids for at least one year. We obtained Visual Analogue Scale for pain score, BMD and plasma LH and FSH in all patients; menstrual history and estradiol in women; free androgen index and total and free testosterone in men. Men were older then women (p<0.05) and had used opioids for a longer period (7.2±3.8 and 4.1±1.8 years, respectively; p<0.05), but there was no difference in opioid dose or pain score between sexes. The prevalence of hypogonadism was high in men (75%), while only 21% of the women reported oligo- or amenorrhea indicating hypogonadism (P<0.01, between sexes). Osteopenia was found in 50% of men and 21% of women (p=NS). We conclude that in CNCP patients receiving chronic opioid therapy there is a much higher prevalence of hypogonadism in men then in women. This needs to be considered clinical practice.

Key words

opioids - hypogonadism - chronic pain - osteopenia/osteoporosis

References

• 1 Abs R, Verhelst J, Maeyaert J, Buyten JP Van, Opsomer F, Adriaensen H, Verlooy J, Havenbergh T Van, Smet M, Acker K Van. Endocrine consequences of long-term intrathecal administration of opioids.  J Clin Endocrinol Metab. 2000;  85 2215-2222
• 2 Adams ML, Sewing B, Forman JB, Meyer ER, Cicero TJ. Opioid-induced suppression of rat testicular function.  J Pharmacol Exp Ther. 1993;  266 323-328
• 3 Azizi F, Vagenakis AG, Longcope C, Ingbar SH, Braverman LE. Decreased serum testosterone concentration in male heroin and methadone addicts.  Steroids. 1973;  22 467-472
• 4 Bliesener N, Albrecht S, Schwager A, Weckbecker K, Lichtermann D, Klingmuller D. Plasma testosterone and sexual function in men receiving buprenorphine maintenance for opioid dependence.  J Clin Endocrinol Metab. 2005;  90 203-206
• 5 Block RI, Farinpour R, Schlechte JA. Effects of chronic marijuana use on testosterone, luteinizing hormone, follicle stimulating hormone, prolactin and cortisol in men and women.  Drug Alcohol Depend. 1991;  28 121-128
• 6 Daniell HW. Hypogonadism in men consuming sustained-action oral opioids.  J Pain. 2002;  3 377-384
• 7 Daniell HW, Lentz R, Mazer NA. Open-label pilot study of testosterone patch therapy in men with opioid-induced androgen deficiency.  J Pain. 2006;  7 200-210
• 8 Ensrud KE, Blackwell T, Mangione CM, Bowman PJ, Bauer DC, Schwartz A, Hanlon JT, Nevitt MC, Whooley MA. Central nervous system active medications and risk for fractures in older women.  Arch Intern Med. 2003;  163 949-957
• 9 Finch PM, Roberts LJ, Price L, Hadlow NC, Pullan PT. Hypogonadism in patients treated with intrathecal morphine.  Clin J Pain. 2000;  16 251-254
• 10 Friedrich G, Nepita W, Andre T. Serum testosterone concentrations in cannabis and opiate users.  Beitr Gerichtl Med. 1990;  48 57-66
• 11 Giri M, Kaufman JM. Opioidergic modulation of in vitro pulsatile gonadotropin-releasing hormone release from the isolated medial basal hypothalamus of the male guinea pig.  Endocrinology. 1994;  135 2137-2143
• 12 Hummer M, Malik P, Gasser RW, Hofer A, Kemmler G, Moncayo Naveda RC, Rettenbacher MA, Fleischhacker WW. Osteoporosis in patients with schizophrenia.  Am J Psychiatry. 2005;  162 162-167
• 13 Kim TW, Alford DP, Malabanan A, Holick MF, Samet JH. Low bone density in patients receiving methadone maintenance treatment.  Drug Alcohol Depend. 2006;  85 258-262
• 14 Kinjo M, Setoguchi S, Schneeweiss S, Solomon DH. Bone mineral density in subjects using central nervous system-active medications.  Am J Med. 2005;  118 1414
• 15 Licata A. Osteoporosis in men: suspect secondary disease first.  Cleve Clin J Med. 2003;  70 247-254
• 16 MacQuay H. Opioids in pain management.  Lancet. 1999;  353 2229-2232
• 17 Morley JE, Patrick P, Perry III HM. Evaluation of assays available to measure free testosterone.  Metabolism. 2002;  51 554-559
• 18 Mussolino ME, Jonas BS, Looker AC. Depression and bone mineral density in young adults: results from NHANES III.  Psychosom Med. 2004;  66 533-537
• 19 O’Loughlin JL, Robitaille Y, Boivin JF, Suissa S. Incidence of and risk factors for falls and injurious falls among the community-dwelling elderly.  Am J Epidemiol. 1993;  137 342-354
• 20 Portenoy RK, Foley KM. Chronic use of opioid analgesics in non-malignant pain: report of 38 cases.  Pain. 1986;  25 171-186
• 21 Vermeulen A. Hormonal cut-offs of partial androgen deficiency: a survey of androgen assays.  J Endocrinol Invest. 2005;  28 28-31
• 22 Vestergaard P, Rejnmark L, Mosekilde L. Fracture risk associated with the use of morphine and opiates.  J Intern Med. 2006;  260 76-87
• 23 Watanabe K, Motoya E, Matsuzawa N, Funahashi T, Kimura T, Matsunaga T, Arizono K, Yamamoto I. Marijuana extracts possess the effects like the endocrine disrupting chemicals.  Toxicology. 2005;  206 471-478

1 Both Authors contributed equally to this publication

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