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DOI: 10.1055/s-0030-1254099
© Georg Thieme Verlag KG Stuttgart · New York
Chronic Use of Opioids and the Endocrine System
Publikationsverlauf
received 24.01.2010
accepted 21.04.2010
Publikationsdatum:
19. Mai 2010 (online)

Abstract
Opioids are widely used for the management of acute and chronic pain. They are also abused for recreational purposes. Long term use may lead to abnormalities in the endocrine system. The axis mainly affected is the gonadal axis leading to hypogonadism. However adrenal insufficiency and growth hormone deficiency can also occur with evidence that other hormones are affected to a lesser extent. No large randomised controlled trials have been performed; however, evidence from several small studies on heroin addicts and chronic pain patients support the above. Hence it is important to consider hormonal abnormalities in patients on long term opioids and if suspected appropriate assessment would be warranted.
Key words
opioids - chronic pain - hypogonadism
References
- 1
Baraka A.
Historical aspects of opium.
MEJ Anaesthesiol.
2000;
15
423-436
Reference Ris Wihthout Link
- 2
Grossman A.
Brain opiates and neuroendocrine function.
Clin Endocrinol Metab.
1983;
12
725-746
Reference Ris Wihthout Link
- 3
Waldhoer M, Bartlett SE, Whistler JL.
Opioid receptors.
Annu Rev Biochem.
2004;
73
953-990
Reference Ris Wihthout Link
- 4
Silberstein SD, McCrory DC.
Opioids.
Cephalalgia.
2000;
20
854-864
Reference Ris Wihthout Link
- 5
Genazzani AR, Genazzani AD, Volpogni C, Pianazzi F, Li GA, Surico N, Petraglia F.
Opioid control of gonadotrophin secretion in humans.
Hum Reprod.
1993;
8
(S 02)
151-153
Reference Ris Wihthout Link
- 6
Howlett TA, Rees LH.
Endogenous opioid peptides and hypothalamo-pituitary function.
Annu Rev Physiol.
1986;
48
527-536
Reference Ris Wihthout Link
- 7
Mendelson JH, Mello NK, Teoh SK, Lloyd-Jones JG, Clifford JM.
Naloxone suppresses buprenorphine stimulation of plasma prolactin.
J Clin Psychopharmacol.
1989;
9
105-109
Reference Ris Wihthout Link
- 8
Cetel NS, Quigley ME, Yen SS.
Naloxone-induced prolactin secretion in women: evidence against a direct prolactin
stimulatory effect of endogenous opioids.
J Clin Endocrinol Metab.
1985;
60
191-196
Reference Ris Wihthout Link
- 9
Steardo L, Monteleone P, Tamminga CA, Canonico PL, Denman D, Scapagnini U, Chase TN.
Differential responses in prolactin levels induced by naloxone in humans.
Psychoneuroendocrinology.
1985;
10
203-209
Reference Ris Wihthout Link
- 10
Baranowska B, Dorobek W, Misiorowski W, Jeske W, Abdel-Fattah MH.
The effect of naloxone on ATCH and beta-endorphin in patients with Cushing's disease.
Acta Endocrinol (Copenh).
1985;
110
170-175
Reference Ris Wihthout Link
- 11
Leslie RD, Prescott RW, Kendall-Taylor P, Cook D, Weightman D, Ratcliffe J, Ingram MC.
Opiate receptor blockade and diurnal pituitary and adrenal hormone levels.
Horm Metab Res.
1985;
17
86-89
Reference Ris Wihthout Link
- 12
Fontana F, Bernardi P, Pich EM, Boschi S, De Iasio R, Spampinato S, Grossi G.
Opioid peptide modulation of circulatory and endocrine response to mental stress in
humans.
Peptides.
1997;
18
169-175
Reference Ris Wihthout Link
- 13
Morris M, Salmon P, Steinberg H, Sykes EA, Bouloux P, Newbould E, McLoughlin L, Besser GM, Grossman A.
Endogenous opioids modulate the cardiovascular response to mental stress.
Psychoneuroendocrinology.
1990;
15
185-192
Reference Ris Wihthout Link
- 14
Brown CH, Scott V, Ludwig M, Leng G, Bourque CW.
Somatodendritic dynorphin release: orchestrating activity patterns of vasopressin
neurons.
Biochem Soc Trans.
2007;
35
1236-1242
Reference Ris Wihthout Link
- 15
Delitala G, Tomasi PA, Palermo M, Ross RJ, Grossman A, Besser GM.
Opioids stimulate growth hormone (GH) release in man independently of GH-releasing
hormone.
J Clin Endocrinol Metab.
1989;
69
356-358
Reference Ris Wihthout Link
- 16
Bang-Ping J.
Sexual dysfunction in men who abuse illicit drugs: a preliminary report.
J Sex Med.
2009;
6
1072-1080
Reference Ris Wihthout Link
- 17
Bliesener N, Albrecht S, Schwager A, Weckbecker K, Lichtermann D, Klingmüller D.
Plasma testosterone and sexual function in men receiving buprenorphine maintenance
for opioid dependence.
J Clin Endocrinol Metab.
2005;
90
203-206
Reference Ris Wihthout Link
- 18
Bai J, Greenwald E, Caterini H, Kaminetzky HA.
Drug-related menstrual aberrations.
Obstet Gynecol.
1974;
44
713-719
Reference Ris Wihthout Link
- 19
Facchinetti F, Volpe A, Farci G, Petraglia F, Porro CA, Barbieri G, Cioni A, Balestrieri A, Genazzani AR.
Hypothalamus-pituitary-adrenal axis of heroin addicts.
Drug Alcohol Depend.
1985;
15
361-366
Reference Ris Wihthout Link
- 20
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
Reference Ris Wihthout Link
- 21
Wang C, Chan V, Yeung RT.
The effect of heroin addiction on pituitary-testicular function.
Clin Endocrinol (Oxf).
1978;
9
455-461
Reference Ris Wihthout Link
- 22
Ragni G, De Lauretis L, Bestetti O, Sghedoni D, Gambaro V.
Gonadal function in male heroin and methadone addicts.
Int J Androl.
1988;
11
93-100
Reference Ris Wihthout Link
- 23
Moshtaghi-Kashanian GR, Esmaeeli F, Dabiri S.
Enhanced prolactin levels in opium smokers.
Addict Biol.
2005;
10
345-349
Reference Ris Wihthout Link
- 24
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;
15
19-29
Reference Ris Wihthout Link
- 25
Lafisca S, Bolelli G, Franceschetti F, Danieli A, Tagliaro F, Marigo M, Flamigni C.
Free and bound testosterone in male heroin addicts.
Arch Toxicol Suppl.
1985;
8
394-397
Reference Ris Wihthout Link
- 26
Celani MF, Carani C, Montanini V, Baraghini GF, Zini D, Simoni M, Ferretti C, Marrama P.
Further studies on the effects of heroin addiction on the hypothalamic-pituitary-gonadal
function in man.
Pharmacol Res Commun.
1984;
16
1193-1203
Reference Ris Wihthout Link
- 27
Daniell HW.
Hypogonadism in men consuming sustained-action oral opioids.
J Pain.
2002;
3
377-384
Reference Ris Wihthout Link
- 28
Daniell HW.
Opioid endocrinopathy in women consuming prescribed sustained-action opioids for control
of nonmalignant pain.
J Pain.
2008;
9
28-36
Reference Ris Wihthout Link
- 29
Daniell HW.
DHEAS deficiency during consumption of sustained-action prescribed opioids: evidence
for opioid-induced inhibition of adrenal androgen production.
J Pain.
2006;
7
901-907
Reference Ris Wihthout Link
- 30
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;
85
2215-2222
Reference Ris Wihthout Link
- 31
Rajagopal A, Vassilopoulou-Sellin R, Palmer JL, Kaur G, Bruera E.
Symptomatic hypogonadism in male survivors of cancer with chronic exposure to opioids.
Cancer.
2004;
100
851-858
Reference Ris Wihthout Link
- 32
Roberts LJ, Finch PM, Pullan PT, Bhagat CI, Price LM.
Sex hormone suppression by intrathecal opioids: a prospective study.
Clin J Pain.
2002;
18
144-148
Reference Ris Wihthout Link
- 33
Behar M, Magora F, Olshwang D, Davidson JT.
Epidural morphine in treatment of pain.
Lancet.
1979;
1
(8115)
527-529
Reference Ris Wihthout Link
- 34
Doleys DM, Dinoff BL, Page L, Tutak U, Willis KD, Coleton M.
Sexual dysfunction and other side effects of intraspinal opiate use in the management
of chronic non-cancer pain.
AJPM.
1998;
8
5-11
Reference Ris Wihthout Link
- 35
Paice JA, Penn RD, Ryan WG.
Altered sexual function and decreased testosterone in patients receiving intraspinal
opioids.
J Pain Symptom Manage.
1994;
9
126-131
Reference Ris Wihthout Link
- 36
Finch PM, Roberts LJ, Price L, Hadlow NC, Pullan PT.
Hypogonadism in patients treated with intrathecal morphine.
Clin J Pain.
2000;
16
251-254
Reference Ris Wihthout Link
- 37
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
Reference Ris Wihthout Link
- 38
Dackis CA, Gurpegui M, Pottash AL, Gold MS.
Methadone induced hypoadrenalism.
Lancet.
1982;
2
(8308)
1167
Reference Ris Wihthout Link
- 39
Pullan PT, Watson FE, Seow SS, Rappeport W.
Methadone-induced hypoadrenalism.
Lancet.
1983;
1
(8326)
714
Reference Ris Wihthout Link
- 40
Camí J, Gilabert M, San L, de la Torre R.
Hypercortisolism after opioid discontinuation in rapid detoxification of heroin addicts.
Br J Addict.
1992;
87
1145-1151
Reference Ris Wihthout Link
- 41
Merza Z, Edwards N, Walters SJ, Newell-Price J, Ross RJ.
Patients with chronic pain and abnormal pituitary function require investigation.
Lancet.
2003;
361
(9376)
2203-2204
Reference Ris Wihthout Link
- 42
Oltmanns KM, Fehm HL, Peters A.
Chronic fentanyl application induces adrenocortical insufficiency.
J Intern Med.
2005;
257
478-480
Reference Ris Wihthout Link
- 43
Mussig K, Knaus-Dittmann D, Schmidt H, Morike K, Haring HU.
Secondary adrenal failure and secondary amenorrhoea following hydromorphone treatment.
Clin Endocrinol (Oxf).
2007;
66
604-605
Reference Ris Wihthout Link
- 44
Hall GM, Lacoumenta S, Hart GR, Burrin JM.
Site of action of fentanyl in inhibiting the pituitary-adrenal response to surgery
in man.
Br J Anaesth.
1990;
65
251-253
Reference Ris Wihthout Link
- 45
Lacoumenta S, Yeo TH, Burrin JM, Bloom SR, Paterson JL, Hall GM.
Fentanyl and the beta-endorphin, ACTH and glucoregulatory hormonal response to surgery.
Br J Anaesth.
1987;
59
713-720
Reference Ris Wihthout Link
- 46
English TN, Ruxton D, Eastman CJ.
Abnormalities in thyroid function associated with chronic therapy with methadone.
Clin Chem.
1988;
34
2202-2204
Reference Ris Wihthout Link
- 47
Chan V, Wang C, Yeung RT.
Effects of heroin addiction on thyrotrophin, thyroid hormones and porlactin secretion
in men.
Clin Endocrinol (Oxf).
1979;
10
557-565
Reference Ris Wihthout Link
- 48
Webster JB, Coupal JJ, Cushman Jr P.
Increased serum thyroxine levels in euthyroid narcotic addicts.
J Clin Endocrinol Metab.
1973;
37
928-934
Reference Ris Wihthout Link
- 49
Brambilla F, Nobile P, Zanoboni A, Zanoboni-Muciaccia W, Meroni PL.
Effects of chronic heroin addiction on pituitary-thyroid function in man.
J Endocrinol Invest.
1980;
3
251-255
Reference Ris Wihthout Link
- 50
Spagnolli W, De Venuto G, Mattarei M, Dal Ri P, Miori R.
Prolactin and thyrotropin pituitary response to thyrotropin releasing hormone in young
female heroin addicts.
Drug Alcohol Depend.
1987;
20
247-254
Reference Ris Wihthout Link
- 51
Shenkman L, Massie B, Mitsuma T, Hollander CS.
Effects of chronic methadone administration on the hypothalamic-pituitary-thyroid
axis.
J Clin Endocrinol Metab.
1972;
35
169-170
Reference Ris Wihthout Link
- 52
Pende A, Musso NR, Montaldi ML, Pastorino G, Arzese M, Devilla L.
Evaluation of the effects induced by four opiate drugs, with different affinities
to opioid receptor subtypes, on anterior pituitary LH, TSH, PRL and GH secretion and
on cortisol secretion in normal men.
Biomed Pharmacother.
1986;
40
178-182
Reference Ris Wihthout Link
- 53
Roti E, Degli Uberti E, Salvadori S, Bianconi M, Emanuele R, Rotola C, Trasforini G, Robuschi G, Tomatis R, Gnudi A, Pansini R, Braverman LE.
Dermorphin, a new opioid peptide, stimulates thyrotropin secretion in normal subjects.
J Endocrinol Invest.
1984;
7
211-214
Reference Ris Wihthout Link
- 54
Delitala G, Grossman A, Besser M.
Differential effects of opioid peptides and alkaloids on anterior pituitary hormone
secretion.
Neuroendocrinology.
1983;
37
275-279
Reference Ris Wihthout Link
- 55
Cushman Jr P.
Growth hormone in narcotic addiction.
J Clin Endocrinol Metab.
1972;
35
352-358
Reference Ris Wihthout Link
- 56
Volpi R, Gerra G, Vourna S, Vescovi PP, Maestri D, Chiodera P, Coiro V.
Failure of the gamma-aminobutyric acid (GABA) derivative, baclofen, to stimulate growth
hormone secretion in heroin addicts.
Life Science.
1992;
51
247-251
Reference Ris Wihthout Link
- 57
Delitala G, Tomasi PA, Palermo M, Ross RJ, Grossman A, Besser GM.
Opioids stimulate growth hormone (GH) release in man independently of GH-releasing
hormone.
J Clin Endocrinol Metab.
1989;
69
356-358
Reference Ris Wihthout Link
- 58
Grossman A, Besser GM, Milles JJ, Baylis PH.
Inhibition of vasopressin release in man by an opiate peptide.
Lancet.
1980;
2
(8204)
1108-1110
Reference Ris Wihthout Link
- 59
Brownell J, del Pozo E, Donatsch P.
Inhibition of vasopressin secretion by a met-enkephalin (FK 33-824) in humans.
Acta Endocrinol (Copenh).
1980;
94
304-308
Reference Ris Wihthout Link
- 60
Zerbe RL, Henry DP, Robertson GL.
A new metenkephalin analogue suppresses plasma vasopressin in man.
Peptides.
1982;
3
199-201
Reference Ris Wihthout Link
- 61
Lindow SW, van der Spuy ZM, Hendricks MS, Nugent FA, Dunne TT.
The effect of morphine and naloxone administration on maternal oxytocin concentration
in late pregnancy.
Clin Endocrinol (Oxf).
1993;
39
671-675
Reference Ris Wihthout Link
- 62
Lindow SW, van der Spuy ZM, Hendricks MS, Rosselli AP, Lombard C, Leng G.
The effect of morphine and naloxone administration on plasma oxytocin concentrations
in the first stage of labour.
Clin Endocrinol (Oxf).
1992;
37
349-353
Reference Ris Wihthout Link
- 63
Lindow SW, Hendricks MS, Nugent FA, Dunne TT, van der Spuy ZM.
Morphine suppresses the oxytocin response in breast-feeding women.
Gynecol Obstet Invest.
1999;
48
33-37
Reference Ris Wihthout Link
- 64
De Leon-Jones FA, Davis JM, Inwang EE, Dekirmenjian H.
Excretion of catecholamine metabolites during methadone maintenance and withdrawal.
Arch Gen Psychiatry.
1983;
40
841-847
Reference Ris Wihthout Link
- 65
Hoehe M, Duka T.
Opiates increase plasma catecholamines in humans.
Psychoneuroendocrinology.
1993;
18
141-148
Reference Ris Wihthout Link
- 66
Pérez-Castrillón JL, Olmos JM, Gómez JJ, Barrallo A, Riancho JA, Perera L, Valero C, Amado JA, González-Macías 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;
72
187-194
Reference Ris Wihthout Link
- 67
Rosen H, Krichevsky A, Bar-Shavit Z.
The enkephalinergic osteoblast.
J Bone Miner Res.
1998;
13
1515-1520
Reference Ris Wihthout Link
- 68
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;
75
998-1000
Reference Ris Wihthout Link
- 69
Elhassan AM, Lindgren JU, Hultenby K, Bergstrom J, Adem A.
Methionine-enkephalin in bone and joint tissues.
J Bone Miner Res.
1998;
13
88-95
Reference Ris Wihthout Link
- 70
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
Reference Ris Wihthout Link
- 71
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;
129
42-45
Reference Ris Wihthout Link
- 72
Vestergaard P, Rejnmark L, Mosekilde L.
Fracture risk associated with the use of morphine and opiates.
J Intern Med.
2006;
260
76-87
Reference Ris Wihthout Link
- 73
Brambilla F, Guerrini A, Guastalla A, Beretta P, Maio DD.
Glucose-insulin metabolism in herion addicts.
Neuropsychobiology.
1976;
2
341-349
Reference Ris Wihthout Link
- 74
Reed JL, Ghodse AH.
Oral glucose tolerance and hormonal response in heroin-dependent males.
Br Med J.
1973;
2
(5866)
582-585
Reference Ris Wihthout Link
- 75
Passariello N, Giugliano D, Ceriello A, Chiariello A, Sgambato S, D’Onofrio F.
Impaired insulin response to glucose but not to arginine in heroin addicts.
J Endocrinol Invest.
1986;
9
353-357
Reference Ris Wihthout Link
- 76
Ceriello A, Giugliano D, Dello Russo P, Sgambato S, D’Onofrio F.
Increased glycosylated haemoglobin A1 in opiate addicts: evidence for a hyperglycaemic
effect of morphine.
Diabetologia.
1982;
22
379
Reference Ris Wihthout Link
- 77
Sadava D, Alonso D, Hong H, Pettit-Barrett DP.
Effect of methadone addiction on glucose metabolism in rats.
Gen Pharmacol.
1997;
28
27-29
Reference Ris Wihthout Link
- 78
Beswick T, Best D, Rees S, Coomber R, Gossop M, Strang J.
Multiple drug use: patterns and practices of heroin and crack use in a population
of opiate addicts in treatment.
Drug Alcohol Rev.
2001;
20
201-204
Reference Ris Wihthout Link
- 79
Johnson RE, Chutuape MA, Strain EC, Walsh SL, Stitzer ML, Bigelow GE.
A comparison of levomethadyl acetate, buprenorphine, and methadone for opioid dependence.
N Engl J Med.
2000;
343
1290-1297
Reference Ris Wihthout Link
- 80
Lawlor PG, Turner KS, Hanson J, Bruera ED.
Dose ratio between morphine and methadone in patients with cancer pain: a retrospective
study.
Cancer.
1998;
82
1167-1173
Reference Ris Wihthout Link
- 81
Chrousos GP, Torpy DJ, Gold PW.
Interactions between the hypothalamic-pituitary-adrenal axis and the female reproductive
system: clinical implications.
Ann Intern Med.
1998;
129
229-240
Reference Ris Wihthout Link
- 82
Frisch RE.
The right weight: body fat, menarche and ovulation.
Baillieres Clin Obstet Gynaecol.
1990;
4
419-439
Reference Ris Wihthout Link
Correspondence
Dr. Z. Merza
Diabetes and Endocrinology
Centre
Barnsley Foundation Hospital
Gawber Road
Barnsley S75 2EP
UK
Telefon: +44/1226/435366
Fax: +44/1226/434406
eMail: z.merza@nhs.net
