Analgesic Efficacy of Testosterone Replacement in Hypogonadal Opioid-treated Chronic Pain Patients: A Pilot Study.

NCT ID: NCT00398034

Last Updated: 2023-10-13

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-10-30
• Study Completion Date: 2007-09-06

Brief Summary

The purpose of this pilot study is to test the effects of testosterone replacement on pain, fatigue, mood, cognition and libido in hypogonadal men on long-term opioid therapy for chronic pain.

Detailed Description

Opioids are increasingly used for the treatment of non-malignant chronic pain with as many as five to ten million patients treated at the time of the most recent estimate in 2002. The side effects of opioids such as fatigue, loss of libido, Impaired cognition and sexual dysfunction have long been recognize and strikingly, resemble symptoms of hypogonadism in men. Many studies have demonstrated a high prevalence of hypogonadism in male subjects who are long-term users of opioids. The aims of this pilot study are, in hypogonadal men being treated with opioids for chronic pain, to: 1) determine the effect of TRT on pain; 2) determine effects of TRT on fatigue; 3) determine the effect of TRT on mood; 4) determine effects of TRT on cognition and 5) characterize the effects of TRT on sexual dysfunction. This study is a randomized, placebo-controlled, 6-week pilot study.

Conditions

Pain; Hypogonadism

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Interventions

Testosterone Gel

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Adult male patients (above 18 years old and below 60 years old)
• Receiving greater than 20 IV morphine equivalents/day with <20% change in dosage in the last month.
• AM total testosterone <300 ng/dL
• Report "worst pain during the past week" grater than 4 on an 11-point numeric scale.

Exclusion Criteria

• Females
• Poorly controlled, symptomatic, active medical or psychiatric problems (e.g., HIV, hepatitis, diabetes, cancer, benign prostatic hypertrophy, substance abuse, major depression)
• Neurological or psychiatric disorder that would compromise the patient's ability to give informed consent or adhere to the requirements of the protocol.
• History of prostate cancer, abnormal findings on digital rectal exam, or PSA greater than 4.0 ng/m
• History of polycythemia
• Renal or hepatic dysfunction
• Hematocrit >55%
• Known history of hypersensitivity to transdermal testosterone gel.
• Abnormalities during digital rectal exam.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Solvay Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

James J. Peters Veterans Affairs Medical Center

FED

Sponsor Role: lead

Responsible Party

Chris Cardozo

Staff Physician

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Christopher P Cardozo, M.D.

Role: PRINCIPAL_INVESTIGATOR

James J. Peters VAMC

References

American Pain Society, Guidelines for the Management of Acute and Cancer Pain. 4 ed. 1999, Glenview, IL: American Pain Society.

Reference Type: BACKGROUND

Portenoy RK. Opioid therapy for chronic nonmalignant pain: a review of the critical issues. J Pain Symptom Manage. 1996 Apr;11(4):203-17. doi: 10.1016/0885-3924(95)00187-5.

Reference Type: BACKGROUND

PMID: 8869456 (View on PubMed)

Rigoni, G. Drug Utilization for Immediate- and Modified Release Opioids in the U.S. in FDA Anesthesia, Life Support, and Addiction Drug Products Advisory Committee. 2003. Gaithersburg, Maryland.

Reference Type: BACKGROUND

Bair MJ, Robinson RL, Katon W, Kroenke K. Depression and pain comorbidity: a literature review. Arch Intern Med. 2003 Nov 10;163(20):2433-45. doi: 10.1001/archinte.163.20.2433.

Reference Type: BACKGROUND

PMID: 14609780 (View on PubMed)

Passchier J, Rupreht J, Koenders ME, Olree M, Luitwieler RL, Bonke B. Patient-controlled analgesia (PCA) leads to more postoperative pain relief, but also to more fatigue and less vigour. Acta Anaesthesiol Scand. 1993 Oct;37(7):659-63. doi: 10.1111/j.1399-6576.1993.tb03784.x.

Reference Type: BACKGROUND

PMID: 8249554 (View on PubMed)

Jarvik LF, Simpson JH, Guthrie D, Liston EH. Morphine, experimental pain, and psychological reactions. Psychopharmacology (Berl). 1981;75(2):124-31. doi: 10.1007/BF00432173.

Reference Type: BACKGROUND

PMID: 6798601 (View on PubMed)

Cicero TJ, Bell RD, Wiest WG, Allison JH, Polakoski K, Robins E. Function of the male sex organs in heroin and methadone users. N Engl J Med. 1975 Apr 24;292(17):882-7. doi: 10.1056/NEJM197504242921703.

Reference Type: BACKGROUND

PMID: 1117911 (View on PubMed)

Crowley TJ, Simpson R. Methadone dose and human sexual behavior. Int J Addict. 1978 Feb;13(2):285-95. doi: 10.3109/10826087809039281.

Reference Type: BACKGROUND

PMID: 640760 (View on PubMed)

Cushman P Jr. Sexual behavior in heroin addiction and methadone maintenance. Correlation with plasma luteinizing hormone. N Y State J Med. 1972 Jun 1;72(11):1261-5. No abstract available.

Reference Type: BACKGROUND

PMID: 4503902 (View on PubMed)

Mintz J, O'Hare K, O'Brien CP, Goldschmidt J. Sexual problems of heroin addicts. Arch Gen Psychiatry. 1974 Nov;31(5):700-3. doi: 10.1001/archpsyc.1974.01760170088014. No abstract available.

Reference Type: BACKGROUND

PMID: 4474860 (View on PubMed)

Smith DE, Moser C, Wesson DR, Apter M, Buxton ME, Davison JV, Orgel M, Buffum J. A clinical guide to the diagnosis and treatment of heroin-related sexual dysfunction. J Psychoactive Drugs. 1982 Jan-Jun;14(1-2):91-9. doi: 10.1080/02791072.1982.10471916.

Reference Type: BACKGROUND

PMID: 7119946 (View on PubMed)

Azizi F, Vagenakis AG, Longcope C, Ingbar SH, Braverman LE. Decreased serum testosterone concentration in male heroin and methadone addicts. Steroids. 1973 Oct;22(4):467-72. doi: 10.1016/0039-128x(73)90002-0. No abstract available.

Reference Type: BACKGROUND

PMID: 4747447 (View on PubMed)

Bolelli G, Lafisca S, Flamigni C, Lodi S, Franceschetti F, Filicori M, Mosca R. Heroin addiction: relationship between the plasma levels of testosterone, dihydrotestosterone, androstenedione, LH, FSH, and the plasma concentration of heroin. Toxicology. 1979 Dec;15(1):19-29. doi: 10.1016/0300-483x(79)90016-7.

Reference Type: BACKGROUND

PMID: 120622 (View on PubMed)

Cushman P Jr. Plasma testosterone in narcotic addiction. Am J Med. 1973 Oct;55(3):452-8. doi: 10.1016/0002-9343(73)90202-7. No abstract available.

Reference Type: BACKGROUND

PMID: 4743346 (View on PubMed)

Mendelson JH, Mendelson JE, Patch VD. Plasma testosterone levels in heroin addiction and during methadone maintenance. J Pharmacol Exp Ther. 1975 Jan;192(1):211-17.

Reference Type: BACKGROUND

PMID: 1123724 (View on PubMed)

Rasheed A, Tareen IA. Effects of heroin on thyroid function, cortisol and testosterone level in addicts. Pol J Pharmacol. 1995 Sep-Oct;47(5):441-4.

Reference Type: BACKGROUND

PMID: 8868137 (View on PubMed)

Afrasiabi MA, Flomm M, Friedlander H, Valenta LJ. Endocrine studies in heroin addicts. Psychoneuroendocrinology. 1979;4(2):145-53. doi: 10.1016/0306-4530(79)90028-3. No abstract available.

Reference Type: BACKGROUND

PMID: 230529 (View on PubMed)

Brambilla F, Sacchetti E, Brunetta M. Pituitary-gonadal function in heroin addicts. Neuropsychobiology. 1977;3(2-3):160-6. doi: 10.1159/000117601.

Reference Type: BACKGROUND

PMID: 331136 (View on PubMed)

Mendelson JH, Mello NK. Plasma testosterone levels during chronic heroin use and protracted abstinence: study of Hong Kong addicts. NIDA Res Monogr. 1978;(19):142-8. No abstract available.

Reference Type: BACKGROUND

PMID: 106283 (View on PubMed)

Ragni G, De Lauretis L, Bestetti O, Sghedoni D, Gambaro V. Gonadal function in male heroin and methadone addicts. Int J Androl. 1988 Apr;11(2):93-100. doi: 10.1111/j.1365-2605.1988.tb00984.x.

Reference Type: BACKGROUND

PMID: 3372047 (View on PubMed)

Cushman P Jr, Kreek MJ. Methadone-maintained patients. Effect of methadone on plasma testosterone, FSH, LH, and prolactin. N Y State J Med. 1974 Oct;74(11):1970-3.

Reference Type: BACKGROUND

PMID: 4528642 (View on PubMed)

Daniell HW. Narcotic-induced hypogonadism during therapy for heroin addiction. J Addict Dis. 2002;21(4):47-53. doi: 10.1300/J069v21n04_05.

Reference Type: BACKGROUND

PMID: 12296501 (View on PubMed)

Lafisca S, Bolelli G, Franceschetti F, Filicori M, Flamigni C, Marigo M. Hormone levels in methadone-treated drug addicts. Drug Alcohol Depend. 1981 Nov;8(3):229-34. doi: 10.1016/0376-8716(81)90066-1.

Reference Type: BACKGROUND

PMID: 6459917 (View on PubMed)

Kley HK, Oellerich M, Wiegelmann W, Herrmann J, Rudorff KH, Nieschlag E, Kruskemper HL. The effect of methadone on hypophyseal and peripheral glandular hormones during withdrawal. Horm Metab Res. 1977 Nov;9(6):484-8. doi: 10.1055/s-0028-1093505. No abstract available.

Reference Type: BACKGROUND

PMID: 412765 (View on PubMed)

Woody G, McLellan AT, O'Brien C, Persky H, Stevens G, Arndt I, Carroff S. Hormone secretion in methadone-dependent and abstinent patients. NIDA Res Monogr. 1988;81:216-23. No abstract available.

Reference Type: BACKGROUND

PMID: 3136363 (View on PubMed)

Daniell HW. Hypogonadism in men consuming sustained-action oral opioids. J Pain. 2002 Oct;3(5):377-84. doi: 10.1054/jpai.2002.126790.

Reference Type: BACKGROUND

PMID: 14622741 (View on PubMed)

Rajagopal A, Vassilopoulou-Sellin R, Palmer JL, Kaur G, Bruera E. Hypogonadism and sexual dysfunction in male cancer survivors receiving chronic opioid therapy. J Pain Symptom Manage. 2003 Nov;26(5):1055-61. doi: 10.1016/s0885-3924(03)00331-2.

Reference Type: BACKGROUND

PMID: 14585556 (View on PubMed)

Abs R, Verhelst J, Maeyaert J, Van Buyten JP, Opsomer F, Adriaensen H, Verlooy J, Van Havenbergh T, Smet M, Van Acker K. Endocrine consequences of long-term intrathecal administration of opioids. J Clin Endocrinol Metab. 2000 Jun;85(6):2215-22. doi: 10.1210/jcem.85.6.6615.

Reference Type: BACKGROUND

PMID: 10852454 (View on PubMed)

Finch PM, Roberts LJ, Price L, Hadlow NC, Pullan PT. Hypogonadism in patients treated with intrathecal morphine. Clin J Pain. 2000 Sep;16(3):251-4. doi: 10.1097/00002508-200009000-00011.

Reference Type: BACKGROUND

PMID: 11014399 (View on PubMed)

Paice JA, Penn RD, Ryan WG. Altered sexual function and decreased testosterone in patients receiving intraspinal opioids. J Pain Symptom Manage. 1994 Feb;9(2):126-31. doi: 10.1016/0885-3924(94)90166-x.

Reference Type: BACKGROUND

PMID: 7517429 (View on PubMed)

Roberts LJ, Finch PM, Pullan PT, Bhagat CI, Price LM. Sex hormone suppression by intrathecal opioids: a prospective study. Clin J Pain. 2002 May-Jun;18(3):144-8. doi: 10.1097/00002508-200205000-00002.

Reference Type: BACKGROUND

PMID: 12048415 (View on PubMed)

Mendelson JH, Inturrisi CE, Renault P, Senay EC. Effects of acetylmethadol on plasma testosterone. Clin Pharmacol Ther. 1976 Mar;19(3):371-4. doi: 10.1002/cpt1976193371.

Reference Type: BACKGROUND

PMID: 1261171 (View on PubMed)

Mendelson JH, Ellingboe J, Judson BA, Goldstein A. Plasma testosterone and luteinizing hormone levels during levo-alpha-acetylmethadol maintenance and withdrawal. Clin Pharmacol Ther. 1984 Apr;35(4):545-7. doi: 10.1038/clpt.1984.75.

Reference Type: BACKGROUND

PMID: 6705455 (View on PubMed)

Yilmaz B, Konar V, Kutlu S, Sandal S, Canpolat S, Gezen MR, Kelestimur H. Influence of chronic morphine exposure on serum LH, FSH, testosterone levels, and body and testicular weights in the developing male rat. Arch Androl. 1999 Nov-Dec;43(3):189-96. doi: 10.1080/014850199262481.

Reference Type: BACKGROUND

PMID: 10624501 (View on PubMed)

Adams ML, Sewing B, Forman JB, Meyer ER, Cicero TJ. Opioid-induced suppression of rat testicular function. J Pharmacol Exp Ther. 1993 Jul;266(1):323-8.

Reference Type: BACKGROUND

PMID: 8392556 (View on PubMed)

Khan C, Malik SA, Iqbal MA. Testosterone suppression by heroin. J Pak Med Assoc. 1990 Jul;40(7):172-3. No abstract available.

Reference Type: BACKGROUND

PMID: 2125664 (View on PubMed)

Malik SA, Khan C, Jabbar A, Iqbal A. Heroin addiction and sex hormones in males. J Pak Med Assoc. 1992 Sep;42(9):210-2.

Reference Type: BACKGROUND

PMID: 1433805 (View on PubMed)

Cicero TJ, Wilcox CE, Bell RD, Meyer ER. Acute reductions in serum testosterone levels by narcotics in the male rat: stereospecificity, blockade by naloxone and tolerance. J Pharmacol Exp Ther. 1976 Aug;198(2):340-6.

Reference Type: BACKGROUND

PMID: 948030 (View on PubMed)

Cicero TJ, Badger TM. A comparative analysis of the effects of narcotics, alcohol and the barbiturates on the hypothalamic-pituitary-gonadal axis. Adv Exp Med Biol. 1977;85B:95-115. doi: 10.1007/978-1-4615-9038-5_8.

Reference Type: BACKGROUND

PMID: 596294 (View on PubMed)

Cicero TJ, Meyer ER, Wiest WG, Olney JW, Bell RD. Effects of chronic morphine administration on the reproductive system of the male rat. J Pharmacol Exp Ther. 1975 Mar;192(3):542-8.

Reference Type: BACKGROUND

PMID: 1168254 (View on PubMed)

Cicero TJ, Bell RD, Meyer ER, Schweitzer J. Narcotics and the hypothalamic-pituitary-gonadal axix: acute effects on luteinizing hormone, testosterone and androgen-dependent systems. J Pharmacol Exp Ther. 1977 Apr;201(1):76-83.

Reference Type: BACKGROUND

PMID: 850146 (View on PubMed)

Cicero TJ, Badger TM, Wilcox CE, Bell RD, Meyer ER. Morphine decreases luteinizing hormone by an action on the hypothalamic-pituitary axis. J Pharmacol Exp Ther. 1977 Dec;203(3):548-55. No abstract available.

Reference Type: BACKGROUND

PMID: 336869 (View on PubMed)

Murphy MR. Methadone reduces sexual performances and sexual motivation in the male Syrian golden hamster. Pharmacol Biochem Behav. 1981 Apr;14(4):561-7. doi: 10.1016/0091-3057(81)90317-8.

Reference Type: BACKGROUND

PMID: 7232476 (View on PubMed)

Mendelson JH, Ellingboe J, Kuehnle J, Mello NK. Heroin and naltrexone effects on pituitary-gonadal hormones in man: tolerance and supersensitivity. NIDA Res Monogr. 1979;27:302-8. No abstract available.

Reference Type: BACKGROUND

PMID: 121347 (View on PubMed)

Mendelson JH, Ellingboe J, Keuhnle JC, Mello NK. Effects of naltrexone on mood and neuroendocrine function in normal adult males. Psychoneuroendocrinology. 1978 Oct;3(3-4):231-6. doi: 10.1016/0306-4530(78)90013-6. No abstract available.

Reference Type: BACKGROUND

PMID: 219434 (View on PubMed)

Catlin DH, Poland RE, Gorelick DA, Gerner RH, Hui KK, Rubin RT, Li CH. Intravenous infusion of beta-endorphin increases serum prolactin, but not growth hormone or cortisol, in depressed subjects and withdrawing methadone addicts. J Clin Endocrinol Metab. 1980 Jun;50(6):1021-5. doi: 10.1210/jcem-50-6-1021.

Reference Type: BACKGROUND

PMID: 7372783 (View on PubMed)

Grossman A. Brain opiates and neuroendocrine function. Clin Endocrinol Metab. 1983 Nov;12(3):725-46. doi: 10.1016/s0300-595x(83)80062-0.

Reference Type: BACKGROUND

PMID: 6323067 (View on PubMed)

Mendelson JH, Meyer RE, Ellingboe J, Mirin SM, McDougle M. Effects of heroin and methadone on plasma cortisol and testosterone. J Pharmacol Exp Ther. 1975 Nov;195(2):296-302.

Reference Type: BACKGROUND

PMID: 1185598 (View on PubMed)

Mirin SM, Meyer RE, Mendelson JH, Ellingboe J. Opiate use and sexual function. Am J Psychiatry. 1980 Aug;137(8):909-15. doi: 10.1176/ajp.137.8.909.

Reference Type: BACKGROUND

PMID: 6774622 (View on PubMed)

Morley JE. The endocrinology of the opiates and opioid peptides. Metabolism. 1981 Feb;30(2):195-209. doi: 10.1016/0026-0495(81)90172-4.

Reference Type: BACKGROUND

PMID: 6258010 (View on PubMed)

Oyama T, Toyota M, Shinozaki Y, Kudo T. Effects of morphine and ketamine anaesthesia and surgery on plasma concentrations of luteinizing hormone, testosterone and cortisol in man. Br J Anaesth. 1977 Oct;49(10):983-90. doi: 10.1093/bja/49.10.983.

Reference Type: BACKGROUND

PMID: 921876 (View on PubMed)

Su CF, Liu MY, Lin MT. Intraventricular morphine produces pain relief, hypothermia, hyperglycaemia and increased prolactin and growth hormone levels in patients with cancer pain. J Neurol. 1987 Dec;235(2):105-8. doi: 10.1007/BF00718020.

Reference Type: BACKGROUND

PMID: 3430186 (View on PubMed)

von Graffenried B, del Pozo E, Roubicek J, Krebs E, Poldinger W, Burmeister P, Kerp L. Effects of the synthetic enkephalin analogue FK 33-824 in man. Nature. 1978 Apr 20;272(5655):729-30. doi: 10.1038/272729a0. No abstract available.

Reference Type: BACKGROUND

PMID: 643067 (View on PubMed)

Cicero TJ. Effects of exogenous and endogenous opiates on the hypothalamic--pituitary--gonadal axis in the male. Fed Proc. 1980 Jun;39(8):2551-4.

Reference Type: BACKGROUND

PMID: 6247215 (View on PubMed)

Purohit V, Singh HH, Ahluwalia BS. Failure of methadone-treated human testes to respond to the stimulatory effect of human chorionic gonadotrophin on testosterone biosynthesis in vitro. J Endocrinol. 1978 Aug;78(2):299-300. doi: 10.1677/joe.0.0780299. No abstract available.

Reference Type: BACKGROUND

PMID: 702024 (View on PubMed)

Ragni G, De Lauretis L, Gambaro V, Di Pietro R, Bestetti O, Recalcati F, Papetti C. Semen evaluation in heroin and methadone addicts. Acta Eur Fertil. 1985 Jul-Aug;16(4):245-9.

Reference Type: BACKGROUND

PMID: 4072581 (View on PubMed)

Couzinet B, Schaison G. The control of gonadotrophin secretion by ovarian steroids. Hum Reprod. 1993 Nov;8 Suppl 2:97-101. doi: 10.1093/humrep/8.suppl_2.97.

Reference Type: BACKGROUND

PMID: 8276977 (View on PubMed)

Martini L, Motta M, Piva F, Zanisi M. LHRF, LHRH, GnRH: what controls the secretion of this hormone? Mol Psychiatry. 1997 Sep;2(5):373-6. doi: 10.1038/sj.mp.4000311.

Reference Type: BACKGROUND

PMID: 9322226 (View on PubMed)

Yen SS, Quigley ME, Reid RL, Ropert JF, Cetel NS. Neuroendocrinology of opioid peptides and their role in the control of gonadotropin and prolactin secretion. Am J Obstet Gynecol. 1985 Jun 15;152(4):485-93. doi: 10.1016/s0002-9378(85)80162-9.

Reference Type: BACKGROUND

PMID: 2990210 (View on PubMed)

Rasmussen DD, Liu JH, Wolf PL, Yen SS. Endogenous opioid regulation of gonadotropin-releasing hormone release from the human fetal hypothalamus in vitro. J Clin Endocrinol Metab. 1983 Nov;57(5):881-4. doi: 10.1210/jcem-57-5-881.

Reference Type: BACKGROUND

PMID: 6311863 (View on PubMed)

Ebeling PR. Osteoporosis in men. New insights into aetiology, pathogenesis, prevention and management. Drugs Aging. 1998 Dec;13(6):421-34. doi: 10.2165/00002512-199813060-00002.

Reference Type: BACKGROUND

PMID: 9883398 (View on PubMed)

Anderson FH. Osteoporosis in men. Int J Clin Pract. 1998 Apr-May;52(3):176-80.

Reference Type: BACKGROUND

PMID: 9684434 (View on PubMed)

Elhassan AM, Lindgren JU, Hultenby K, Bergstrom J, Adem A. Methionine-enkephalin in bone and joint tissues. J Bone Miner Res. 1998 Jan;13(1):88-95. doi: 10.1359/jbmr.1998.13.1.88.

Reference Type: BACKGROUND

PMID: 9443794 (View on PubMed)

Perez-Castrillon JL, Olmos JM, Gomez JJ, Barrallo A, Riancho JA, Perera L, Valero C, Amado JA, Gonzalez-Macias J. Expression of opioid receptors in osteoblast-like MG-63 cells, and effects of different opioid agonists on alkaline phosphatase and osteocalcin secretion by these cells. Neuroendocrinology. 2000 Sep;72(3):187-94. doi: 10.1159/000054586.

Reference Type: BACKGROUND

PMID: 11025413 (View on PubMed)

Rico H, Costales C, Cabranes JA, Escudero M. Lower serum osteocalcin levels in pregnant drug users and their newborns at the time of delivery. Obstet Gynecol. 1990 Jun;75(6):998-1000.

Reference Type: BACKGROUND

PMID: 2342747 (View on PubMed)

Pedrazzoni M, Vescovi PP, Maninetti L, Michelini M, Zaniboni G, Pioli G, Costi D, Alfano FS, Passeri M. Effects of chronic heroin abuse on bone and mineral metabolism. Acta Endocrinol (Copenh). 1993 Jul;129(1):42-5. doi: 10.1530/acta.0.1290042.

Reference Type: BACKGROUND

PMID: 8351958 (View on PubMed)

Miller K, Corcoran C, Armstrong C, Caramelli K, Anderson E, Cotton D, Basgoz N, Hirschhorn L, Tuomala R, Schoenfeld D, Daugherty C, Mazer N, Grinspoon S. Transdermal testosterone administration in women with acquired immunodeficiency syndrome wasting: a pilot study. J Clin Endocrinol Metab. 1998 Aug;83(8):2717-25. doi: 10.1210/jcem.83.8.5051.

Reference Type: BACKGROUND

PMID: 9709937 (View on PubMed)

Forman LJ, Tingle V, Estilow S, Cater J. The response to analgesia testing is affected by gonadal steroids in the rat. Life Sci. 1989;45(5):447-54. doi: 10.1016/0024-3205(89)90631-0.

Reference Type: BACKGROUND

PMID: 2770410 (View on PubMed)

Frye CA, Seliga AM. Testosterone increases analgesia, anxiolysis, and cognitive performance of male rats. Cogn Affect Behav Neurosci. 2001 Dec;1(4):371-81. doi: 10.3758/cabn.1.4.371.

Reference Type: BACKGROUND

PMID: 12467088 (View on PubMed)

Stoffel EC, Ulibarri CM, Craft RM. Gonadal steroid hormone modulation of nociception, morphine antinociception and reproductive indices in male and female rats. Pain. 2003 Jun;103(3):285-302. doi: 10.1016/s0304-3959(02)00457-8.

Reference Type: BACKGROUND

PMID: 12791435 (View on PubMed)

Other Identifiers

2192-06-049

Identifier Type: -

Identifier Source: org_study_id