Influence of substance use on male reproductive health and offspring outcomes

• Published in: Nature reviews. Urology Vol. 21; no. 9; pp. 534 - 564
• Main Authors: Lo, Jamie O., Hedges, Jason C., Chou, Wesley H., Tager, Kylie R., Bachli, Ian D., Hagen, Olivia L., Murphy, Susan K., Hanna, Carol B., Easley, Charles A.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-09-2024; Nature Publishing Group
• Subjects: 692/308/409; 692/4025/2021; 692/499; COVID-19 - epidemiology; Drug use; Female; Humans; Infertility, Male - epidemiology; Infertility, Male - etiology; Male; Medicine; Medicine & Public Health; Narcotics; Pregnancy; Prenatal Exposure Delayed Effects; Public health; Reproductive Health; Review Article; Substance-Related Disorders - epidemiology; Urology; Central America
• ISSN: 1759-4812; 1759-4820; 1759-4820
• DOI: 10.1038/s41585-024-00868-w

The prevalence of substance use globally is rising and is highest among men of reproductive age. In Africa, and South and Central America, cannabis use disorder is most prevalent and in Eastern and South-Eastern Europe, Central America, Canada and the USA, opioid use disorder predominates. Substance use might be contributing to the ongoing global decline in male fertility, and emerging evidence has linked paternal substance use with short-term and long-term adverse effects on offspring development and outcomes. This trend is concerning given that substance use is increasing, including during the COVID-19 pandemic. Preclinical studies have shown that male preconception substance use can influence offspring brain development and neurobehaviour through epigenetic mechanisms. Additionally, human studies investigating paternal health behaviours during the prenatal period suggest that paternal tobacco, opioid, cannabis and alcohol use is associated with reduced offspring mental health, in particular hyperactivity and attention-deficit hyperactivity disorder. The potential effects of paternal substance use are areas in which to focus public health efforts and health-care provider counselling of couples or individuals interested in conceiving.
Paternal substance use is associated with adverse effects on male reproductive health and offspring health outcomes. Comprehensive counselling by health-care providers and improved public health measures, especially targeting reproductive-age men, are needed.
Key points
Alcohol consumption, especially chronic and heavy intake, alters the hypothalamic–pituitary–gonadal axis, male reproductive hormones, semen parameters, testicular damage and results in decreased sexual function.
Cannabis use adversely affects male fertility, resulting in substantial testicular atrophy, altered reproductive hormones, and changes in semen parameters.
Opioid abuse can negatively affect male reproductive hormones and spermatogenesis, and is associated with an increased risk of reduced testicular volume and erectile dysfunction.
Nicotine smoke is linked to impaired semen parameters and erectile dysfunction, and seems to follow a dose-dependent pattern.
Preconception paternal alcohol intake is associated with adverse short-term and long-term offspring outcomes, including birth defects, growth abnormalities, neurodevelopmental disorders and addiction vulnerability.
Preconception paternal cannabis use has been linked to increased rates of pregnancy loss, decreased infant birthweight and offspring behavioural problems, including poor attention.