The Impact Of Substance Use Disorders On Sex Hormone Levels: A Systematic Review Of Human Studies
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Keywords
Substance use disorder, sex hormones, testosterone, estrogen, opioids, alcohol, cannabis, endocrine dysfunction, hypogonadism.
Abstract
Background: Substance use disorders (SUDs) are chronic, relapsing conditions that affect multiple physiological systems, including the neuroendocrine axis. Emerging evidence suggests that alcohol, opioids, cannabis, stimulants, and other psychoactive substances can significantly alter sex hormone levels, contributing to reproductive dysfunction, sexual behavior changes, and systemic metabolic disturbances. Objective: This systematic review aimed to evaluate the impact of various substance use disorders on circulating levels of key sex hormones—testosterone, estrogen, progesterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH)—in human populations. Methods: A systematic search was conducted across PubMed, Scopus, Web of Science, and PsycINFO databases from inception to September 2025. Eligible studies included human clinical or observational research examining hormonal changes associated with substance use or withdrawal. Data extraction focused on hormone level alterations, sample characteristics, duration and type of substance use, and potential confounders such as age, sex, and comorbidities. The methodological quality of included studies was assessed using the Newcastle–Ottawa Scale for observational designs and the Cochrane Risk of Bias tool for clinical trials. Results: A total of 62 studies involving 8,400 participants met inclusion criteria. Chronic alcohol consumption was consistently associated with decreased testosterone and elevated estrogen levels in men, along with menstrual irregularities in women. Opioid dependence led to significant suppression of gonadotropin-releasing hormone (GnRH), LH, and FSH, resulting in secondary hypogonadism. Cannabis use showed dose-dependent effects, with reductions in testosterone and altered estradiol levels, though findings varied by duration and frequency of use. Stimulant use (e.g., cocaine, methamphetamine) produced inconsistent hormonal effects but frequently disrupted menstrual cycles and libido. Recovery or abstinence periods were linked to partial normalization of hormone levels. Conclusion: Substance use disorders exert substantial, substance-specific effects on sex hormone regulation, often leading to hypogonadism and reproductive dysfunction. These endocrine disruptions may exacerbate the physical and psychological complications of addiction. Clinicians should consider hormonal assessment as part of comprehensive care for individuals with SUDs. Further longitudinal studies are needed to clarify the reversibility of these effects and to establish standardized endocrine monitoring protocols in addiction treatment settings.
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References
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