Volume 5, Issue 2 (7-2007)                   IJRM 2007, 5(2): 35-38 | Back to browse issues page

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Hejazian S H, Dashti M H, Rafati A. The effect of opium on serum LH, FSH and testosterone concentration in addicted men. IJRM 2007; 5 (2) :35-38
URL: http://ijrm.ir/article-1-58-en.html
1- Department of physiology, Shahid Sadoughi University of Medical Sciences, Yazd, Iran , hejaziansh@yahoo.com
2- Department of physiology, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
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Addiction is a problem which is increasingly developed among the various populations throughout the world (1,2). In western societies the major source of drug abuse is heroine (3,4). Therefore most of the research on addiction is focused on the effects of this agent on body systems (1,4) but in Iran opium is the most popular drug among addicted subjects (5-7). Various factors including social, economical and cultural  factors are involved in addiction to opium and other morphine  containing substances. In  the case of gender D,souza  et al (2002) tested the overall hypothesis that circulating gonadal steroids are responsible for the gender differences in morphine induced behavior (8). They reported that morphine causes a greater expression of C-fos in the striatum of males than that of females. They concluded that there is a significant sex differences in response to morphine. Also it has been mentioned that there is a relationship between the morphine consumption and steroid hormones. Yan and Hou (2004) found that chronic morphine administration resulted in a marked decrease in the brain concentration of steroids in Rat (9). In the other hand, Peters and Wood (2005) reported that the depressant effect of high dose of steroid hormones on autonomic nervous system is partly mediated by an opioidergic mechanism (10). This evidence suggested that there is a significant interaction between morphine and steroid hormones in those who are exposed to the opioid agents. This may be directly through its action on gonads or via hypothalamic-hypophysiol-gonadal axis. The gonadotropines (LH, FSH) are pulstily released from hypothalamus and acts via hypotalamo-hypophysio-gonadal axis which stimulate gonadal endocrine function and gametogenesis in males. This activity leads to proper spermatogenesis and male sexual responses (11). Suppression of this axis will lead to reduction of sperm count, semen quality, impairment of erection and finally infertility (12).  Now a days opioids are increasingly consumed as drug of abuse (1,13,14). Despite many researches on the effects of morphine on different body systems, the effects of long term opium consumption on endocrine system especially on sex hormones are not well studied, therefore we studied the effects of opium addiction on testosterone and gonadotropines in addicted men.
Material and methods
     In this study, 46 opioied addicted 23-48 years old men who had a history of 1-15 years of opium consumption, were randomly selected from Kerman Rehabilitation Center as the test group. At the same time 46 non addicted men with the same including and excluding criteria such as age range, cigarette smoking, social and cultural conditions were selected as the control group. Blood samples were collected from all subjects and serum specimens collected from these samples were frizzed at –20oC. After collection of all specimens, serum levels of free testosterone, LH and FSH were measured by radioimmunoassay (RIA) technique by a LKB gamma counter.
Statistical Analysis
     Data were expressed as mean±SEM for serum levels of testosterone, LH and FSH. Data were statistically analyzed by using student’s t-test and ANOVA using SPSS software. P values less than 0.05 were considered to be significance. 
     Considering the duration of addiction to opium indicates that the most frequent duration (32.6%) was 10-12 years among this population (table I). According to age, subjects in control group (35.05±7.33 years) were matched with test group (36.2±6.95 years). Mean values for serum levels of testosterone, LH and FSH from all subjects in control and test groups are shown in Table II. Our data indicate that testosterone, LH and FSH hormones were significantly declined in test group as compared with control group (p<0.01, p<0.01 and p<0.05 respectively). The minimum value for serum testosterone was measured in subjects who had a history of 13-15 years of addiction (9.8±3.3 mmol/L) which was significantly (p<0.01) less than subjects who had the least duration of addiction (23.2±3.8 mmol/L). Similarly, along with the increase in duration of addiction serum level of LH was significantly reduced (4.9 mIU/ml for 13-15 years addicted subjects vs. 5.9 mIU/ml for one year addicted subjects, p<0.01). Also the results obtained from the regression test indicate that there is a positive correlation between duration of addiction and the decline in the serum levels of testosterone and LH in test group but there was no correlation between the reduction in FSH level and the duration of addiction (3.5 mIU/ml for 13-15 years addicted subjects vs. 4.8 mIU/ml for one year addicted subjects (Table III).

     Changes in the sexual activity are commonly found in addicted subjects. The effects of drug abuse on sexual functions and sex hormones are one of the major scopes of investigations throughout the world. Since heroin and cocaine consumption is the most popular drug of abuse in western countries the majority of studies have focused on heroin and cocaine addicted subjects (3,4,15). In the case of cocaine many studies have mentioned a significant correlation between cocaine abuse and the reduction in hypothalamo-pituitary gonadal function (16,17). Festa et al (2003) reported that administration of cocaine in Fischer rats affects the endocrine response in both male and female rats and leads to a significant decrease in testosterone level (15). In Contrast, Mendelson (2003) found that despite a significant increase in LH release by intravenous administration of Cocaine there was no change in the testosterone level in men (17). Azizi et al (1973) in a clinical trial study found that there is a decreased in serum levels of testosterone in male heroin and methadone addicts (1). Also Finch et al (2000) suggested that intrathecal opioid therapy in both men and pre menopausal and postmenopausal women led to hypogonadism with low level of serum testosterone or estrogen coupled with low level of gonadotropines (18). Celani et al (1984) in a study on the effect of heroin addiction on the hypothalmo–pituitary gonadal function in men indicated that mean basal values of LH biological activity, and  immunoreactive LH in heroein addicts were similar to those obtained in the control group but serum levels of free testosterone were significantly reduced in heroine addicts (4).
     Our findings indicate that in the case of chronic opium consumption there is a significant decrease in serum levels of LH, FSH and testosterone and this reduction was positively co-related with the duration of opium consumption. These findings are in accordance with the Estienne et al  (2002) findings (19).They suggest that opioid peptides suppress LH secretion and stimulate GH release in sexually mature Boars. Since Moshtaghi et al (2005) indicated that there is a positive co-relation between the dose of opium and the plasma prolactin level (as an inhibitor of GnRH) in opium dependents (20), thus the suppression of gonadotropine secretion by adenohypophysis may be due to suppression of GnRH release from the hypothalamus. However there are some reports suggesting the direct effects of opium on pituitary gonadotropine releasing cells via kappa (21) and mu (22) opioid receptors. Since there are some report’ suggesting that opium, heroin and methadone could not decreased testosterone level (1,23), the decrease in plasma testosterone level in the present study may be secondary to the suppression of LH and FSH release in opium addicted subjects.
Type of Study: Original Article |

1. Azizi F, Vagenakis AG, Longcope C, Ingbar SH, Braverman LE. Decreased serum testosterone concentration in male heroin and methadone addicts. Steroid 1973; 22: 467-472. [DOI:10.1016/0039-128X(73)90002-0]
2. Blank M, Fabrri A. Inhibition of LH release by morphine and endogenous Opiates in cultured pituitary cells. Endocrinology 1986; 118: 2097-2101. [DOI:10.1210/endo-118-5-2097]
3. Mendelson JH, Meyar RF, Ellingboe J, Mirin SM, McDougle M. Effects of Heroin and Methadone of plasma cortisol and testostrone. J Pharmacol Exp ther 1975; 195: 296-302.
4. Celani MF, Carani C, Montanini V, Baraghini GF, Zini D, Simoni M, et al. Further studies on the effects of heroin addiction on the hypothalamic-pituitary-gonadal function in man. Pharmacol Res Commun 1984; 16: 1193. [DOI:10.1016/S0031-6989(84)80084-3]
5. Ahmadi J, Ghandizadeh A. Current substance use among Iranian medical students. Indian J of Psychiatry 2001; 43: 157-161.
6. Azarakhash MD. Brief overview of the status of drug abuse in Iran. Arch Iranian Med 2002; 5: 184-190.
7. Rajabizade G, Remezani M, Shakibi M. Prevalence of opium addiction in Iranian drivers. J Med Sci 2004; 4: 210-213. [DOI:10.3923/jms.2004.210.213]
8. D'souza DN, Harlan RE, Garcia MM. Sexually dimorphic effects of morphine and MK-801 sex steroid dependent and independent mechanism. J Appl Physiol 2002; 92: 493-503. [DOI:10.1152/japplphysiol.00565.2001]
9. Yan CZ, Hou YN. Effect of morphine dependence and withdrawal on levels of neurosteroids in rat brain. Acta Pharmacol Sin 2004; 25: 1285-1291.
10. Peters KD, Wood RI. Androgen dependence in hamsters, tolerance, and potential opioidergic mechanism. Neuroscience 2005; 130: 971-981. [DOI:10.1016/j.neuroscience.2004.09.063]
11. Ganong WF. Review of medical physiology. 21th ed, Stamford: Appleton & Lange, 2003: 393-414.
12. Antony SF. Hormone's principles of internal medicine. 16th ed, 2005; 1: 1648-1812. [DOI:10.4183/aeb.2005.499]
13. Hollister LE: Drugs of abuse, in katzung BG: Basic & clinical pharmacology, 6th ed, Norwalk, Appleton & Lagne, 1995; 478-491.
14. Jaffe JH. Drug addiction and drug abuse. In Goodman Gilman A, Rall TW (eds) Goodman & Gilmans the pharmacological basis of therapeutics. 8th ed. New York, pergamon press, 1991; 532-535.
15. Festa ED, Jenab S, Chin J, Gazi FM, Wu HB, Russo SJ, Quinones-Jenab V. Frequency of cocaine administration affects behavioral and endocrine responses in male and femalefischerrats. Cell Mol Biol (Noisy-le- grand). 2003; 49: 1275-1280.
16. Mendelson JH, Mello NK, Sholar MB, Siegel AJ, Mutshler N, Halpern J. Temporal conductance of cocaine effects on mood statium and neuroendocrine hormone. Spsynchoendocrinalogy 2002; 71-82. [DOI:10.1016/S0306-4530(01)00036-1]
17. Mendelson JH, Sholar MB, Mutschler NH, Jaszyna-Gasior M, Goletiani NV, Siegel AJ, Mello NK. Effects of Intravenous Concaine and Cigarette smoking on luteinizing Hormone, testosterone, and prolactin in men. J Pharmacol Exp Ther 2003; 307: 339-348. [DOI:10.1124/jpet.103.052928]
18. Finch PM, Robers L, Price L, Hadlow NC, Pullan PT. Hypogonadism in patients treated with intrathecal morphine. Clin J Pain 2000; 16: 251-254. [DOI:10.1097/00002508-200009000-00011]
19. Estienne MJ, Harper AF, Knight JW, Rampacek GB, Barb CR. Circulating concentration of LH, testosterone and GH after naloxane treatment in sexually mature boars. Reprod Biol 2002; 2: 133-142.
20. Moshtaghi-Kashanian GR, Esmaeeli F, Dabiri S. Enhanced prolactin levels in opium smokers. Addict Biol 2005; 10: 345-349. [DOI:10.1080/13556210500351263]
21. Zhang Q, Gallo RV. Presence of kappa opioid tone at the onset of the ovulatory LH surge in proesterous Rat. Brain res 2003; 980: 135-139. [DOI:10.1016/S0006-8993(03)02965-2]
22. Sokolowska-Mikolajczyk M, Socha M, Mikolajczyk T, Chyb J, Szymacha J, Epler P. Differential effects of morphine and naltrexone on the in vitro LH secretion from male and female carp pituitary gland. Comp Biochem Physiol C Toxicol Pharmacol 2005; 141: 325-331. [DOI:10.1016/j.cbpc.2005.09.001]
23. Bliensener N, Albrecht S, Schwager A, Weckbecker K, Lichtermann D, Klingmuller D. Plasma testosterone and sexual function in men receiving buprenorphine maintain for opioid dependence. J Clin Endocrinol metab 2005; 90: 203-206. [DOI:10.1210/jc.2004-0929]

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