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Influence of substance use on male reproductive health and offspring outcomes

Nature Reviews Urology volume 21, pages 534–564 (2024)Cite this article

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Abstract

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.

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.

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Acknowledgements

J.O.L. is funded by NIH NIDA DP1 DA056793. C.A.E. is funded by NIH OD R01OD028223 and was previously funded by NIH NIEHS K22ES025418.

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  1. These authors contributed equally: Jamie O. Lo, Jason C. Hedges.

Authors and Affiliations

  1. Department of Urology, Oregon Heath & Science University, Portland, OR, USA

    Jamie O. Lo, Jason C. Hedges & Wesley H. Chou

  2. Division of Reproductive & Developmental Sciences, Oregon National Primate Research Center, Oregon Health & Science University, Portland, OR, USA

    Jamie O. Lo, Jason C. Hedges, Olivia L. Hagen & Carol B. Hanna

  3. Department of Obstetrics and Gynecology, Oregon Health & Science University, Portland, OR, USA

    Jamie O. Lo & Jason C. Hedges

  4. Department of Environmental Health Science, University of Georgia College of Public Health, Athens, GA, USA

    Kylie R. Tager, Ian D. Bachli & Charles A. Easley IV

  5. Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC, USA

    Susan K. Murphy

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Contributions

J.O.L., J.C.H., W.H.C., K.R.T., I.D.B. and C.A.E. researched data for the article. All authors contributed substantially to discussion of the content. J.O.L., J.C.H., W.H.C., K.R.T., I.D.B. and C.A.E. wrote the article. All authors reviewed and edited the manuscript before submission.

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Correspondence to Jamie O. Lo.

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Lo, J.O., Hedges, J.C., Chou, W.H. et al. Influence of substance use on male reproductive health and offspring outcomes. Nat Rev Urol 21, 534–564 (2024). https://doi.org/10.1038/s41585-024-00868-w

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