الفهرس 
IntroductionOnly 14 pages are availabe for public view
Abstract
S
ubstance use and dependence cause a significant burden to individuals and societies throughout the world. Opioid dependency has increased in prevalence over the last few decades, particularly in the Middle East, including Egypt.
A 2007 National Survey report stated that 8.5% of Egyptians - or six million people - are addicted to drugs and that the majority of them are between 15 and 25 years old.
While 2014 National Survey report stated that 0.2% the Egyptian population above the age of 15. A proportion of 19.3% were experimental users, 6.7% were regular on substance use, while 6.4% were fulfilling the criteria of dependence.
Among a range of potential side effects of opiates misuse, SD is common and clinically significant. Psychoactive substances are believed in many cultures to be of aphrodisiac function; but in reality they have deleterious effects on all the aspects of sexual and hormonal functions. Whether withdrawal from the substances could restore erectile function remains unknown.
Compared with the general population, studies with regular heroin users, revealed decreased libido reported in the majority of addicts, erectile dysfunction in 39∼48% and delayed ejaculation in over 50% of the addicts.
Current knowledge is briefly reviewed about the role of the opioid system in the regulation of reproductive physiology, at multiple levels; at the levels of the central nervous system, at the testes level and at sperm level.
Evidence suggests that opioids – both endogenous and exogenous – can bind to opioid receptors primarily in the hypothalamus, but potentially also in the pituitary and the testes, to modulate gonadal function. Decreased release, or interference with the normal pulsatility of release of GNRH at the level of the hypothalamus, has been documented, with consequent decreased release of LH and FSH from the pituitary. Direct effects of opioids on the testes, including decreased secretion of testosterone and testicular interstitial fluid, have been documented as well.
The relationship between psychoactive substances and sexual behavior are complex. Caution should be taken when interpreting research on the effects of drugs on sexual function, as psychological, physiological, environmental, or cultural factors may be associated with use of a particular substance, and may have independent or intervening effects.
Moreover, although tramadol was thought to have low abuse potentials worldwide, its abuse has become a serious problem in many countries, particularly in the Middle East. Tramadol HCl dependency is at the top of all substances abused after cannabis in Egypt, at frequency of 49%, followed by polysubstances at 43%.
Despite the high prevalence of SD in addicted opiate users, only a few studies on SD with these patients have been undertaken in Egypt. As a result, the importance of SD in this vulnerable group has been underestimated. And to the best of our knowledge, none of previous studies was conducted on atypical opioids such as tramadol.
Therefore, we attempted to investigate the sexual functioning of males using tramadol and its relationship to levels of free testosterone, LH, and FSH sex hormones and to compare them with heroin addicts and healthy controls. This is one of the rare studies discussing this important problem in Egypt.
We hyposethized, that there is a significant prevalence of sexual dysfunction and decrease in testosterone level, LH & FSH in opiate abusers (tramadol HCL and heroin).
Aim of the work:
To verify the hypothesis, and to evaluate the following points if the hypothesis is verified:
1- To evaluate the risk of sexual dysfunction in patients with opiates abuse disorder.
2- To evaluate the correlation of opiates abuse disorders and decrease in testosterone, LH & FSH levels.
3- To compare and detect if there a difference in sexual dysfunction, free testosterone level, LH & FSH between tramadol HCL dependence and heroin dependence
4- To assess the characteristics of opiate abuse in patients with sexual dysfunction
The study comprises 60 male patients with opioid dependency (30 heroin and 30 tramadol HCL use disorders patients) and 30 healthy controls, presenting to the both OPCs and inpatient addiction unit of Ain Shams University psychiatry department, Cairo, Egypt, from January 2015 until January 2016.
Subjects involved in the study were assessed using:
1- Structured clinical interview for DSM-IV Axis I Disorder (SCID-I) (Arabic version).
2- Addiction Severity Index (5thed.) for addicts only (Arabic version ).
3- International Index of Erectile Function (IIEF) a multidimensional scale (Arabic version)
4- Free testosterone, FSH and LH levels will be measured in blood samples (morning samples) of patients and will be measured by using ELISA.
The main findings of this study were:
Regarding the hormonal profile of opiate dependents, in comparison with healthy controls, both heroin and tramadol use disorders decreased LH and free testosterone level significantly compared to healthy controls. Patients using heroin had significantly lower levels than those using tramadol, indicating that heroin suppressant effect on these hormones was more, which could be explained by lower affinity of tramadol HCl to opioid receptors, which could affect how opioids influence testosterone levels.
It is noteworthy, that despite the presence of hypotestosteronemia, serum levels of LH did not increase; a pattern compatible with an inhibiting influence on GnRH production by opioids, which can result in a hypogonadotropic hypogonadism state.
However, their effect on FSH was conflicting, where heroin use patients had lower levels than that of controls and tramadol use patients had surprisingly higher levels than healthy controls. This agrees with, several data demonstrating that FSH levels are not influenced by opioid administration significantly.
Regarding Sexual dysfunctions across the two groups of opiate dependents, in comparison with healthy controls, the finding of high prevalence of SD in opioid use disorder patients (both groups) compared to healthy controls, suggests that active use of opioids is associated with significant SD.
The above findings also suggest that opioids cause generalized sexual dysfunction, rather than affecting specific domains, with the most effect being in erectile dysfunction.
In addition, the current results propose that heroin use effect on sexual dysfunction involving its multiple domains is more profound than that of tramadol HCL use disorder. Yet, both cause deterioration of sexual functioning in comparison to healthy controls.
Regarding sex hormone levels and their correlation to sexual dysfunction, in agreement with other studies demonstrating that, endocrinal causes to be responsible only for a small number of cases of SD in the general, the present study found No significant correlation between the hormonal profile and the sexual functions of both subjects.
Concerning the association of patients and SUD characteristics and sexual function in opioids illicit use patients:
Regarding heroin use disorder patients, a significant negative correlation between SD was observed with the age of the patients and the age of onset of heroin use.
In addition, there is a significant negative correlation between the free testosterone level and the duration of substance use in heroin addicts. However, no significant correlation was found between duration of use of heroin and sexual functioning.
Regarding tramadol HCL use disorder patients, there no significant correlation was found between the age of patients and sexual functions, nor with the age of onset of problematic tramadol HCL use.
Moreover, no significant correlation was found between the duration of the use of tramadol HCL with the sexual functions. Yet, a highly significant negative correlation between the free testosterone level and the duration of use was found.
Regarding both heroin and tramadol use disorder groups, no significant correlation between the daily dose and the sex hormone levels or sexual functions scores were observed in this study.
In conclusion, the widespread belief by our culture about tramadol’s value in improving sexual and physical function was proved wrong. These findings are of ultimate importance considering the fact that people use opioids to enhance their sexual performance in our country. There is a need to increase the awareness of clinicians about this association as many times SD in patients with substance abuse lead to poor treatment compliance and relapse.