International Journal of

     Introduction
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.      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 –20^oC. 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. 
 
Results
 
     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).



 
Conclusion
 
     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.