Background and aims: Tramadol and methadone are synthetic opioid drugs that are widely used in various fields of medicine. This review article was performed to investigate the hormone disturbance of long-term tramadol and methadone use in women. Methods: Keywords were determined using the MeSH browser and then searched in ISI, Scopus, EMBASE, and PubMed databases on 25.5.2022. The articles with non-English language, articles whose full text was not retrieved, and studies that were irrelevant to the aim of this study were excluded from the investigation. Results: Methadone and tramadol affected a sexual hormone in women through an impact on the hypothalamic-pituitary-gonadal axis. They could reduce the levels of follicle stimulating hormone and luteinizing hormone, increase prolactin production, and finally, reduce gonadal steroids. Opioids also could influence thyroid and adrenal glands and subsequently increase thyroid-stimulating hormone, and reduce dehydroepiandrosterone. Eventually, this mechanism caused a disturbance in sexual hormone disturbance in women. Conclusion: Overall, long-term methadone and tramadol consumption as opioid substances could cause sexual hormone disturbance in women.