Objectives: Drug addiction becomes one of the grave problems worldwide, which has much health adverse effects. There are many reports relating Sexual dysfunction to heroin addiction that also affecting sex hormones. The aim of this study was to investigate the association of sexual dysfunction, expression of sex hormones related genes and sex hormones disturbance with illicit heroin addiction in patients presented to psychiatric outpatient clinic, Zagazig University Hospitals, Egypt. Methods: Semi-structured questionnaire and International index of erectile function scale were used for assessment of erectile and sexual dysfunction of 180 adult males (90 heroin addicts and 90 controls). Then the heroin addiction group was subdivided into (Initiation of heroin withdrawal group and 6-months follow up group, 45 individuals in each subgroup. Blood samples were collected for detection of sex hormones (Testosterone, FSH and LH) by Electrochmeiluminescence analyzer, genes expression of (Cytochrome 19 (CYP19), Follicle Stimulating Hormone related gene (FSH-B), Luteinizing Hormone related gene (LH-B) by Quantitative Real-time polymerase chain reaction(RT-PCR). Results: heroin addicts suffered from a matter of sexual dysfunction as (decrease erectile function, orgasm, sexual desire and intercourse satisfaction), reduction of serum sex hormones and up regulation of CYP19 gene, down regulation of FSH-B and LH-B genes. Conclusion: This study suggested that there is a correlation between heroin addiction and sexual dysfunction with reduction of sex hormones secondary to affection of sex hormone related genes that showed improvement in the group of heroin discontinuation for 6 months