Substance use and male fertility Original paper

Infertility is defined as the inability to become pregnant after 12 months of regular unprotected intercourse. Approximately 20–30% of infertility cases are directly attributed to men, but men contribute to them as a whole at a rate of about 50%.

Male infertility has been rigorously studied over the past few decades, but the research has primarily focused on physiological factors (e.g., genetic/chromosomal outliers). There is a stark lack of evidence on other factors that may contribute to male infertility (e.g., those classified as environmental and behavioral) including addictions (term used by the study authors; aka substance use disorders), which could be placed under both categories.

This systematic review assessed 65 research studies published before May 2021. The studies were categorized according to the type of substance use:

• Opioids/cannabinoids (18 studies)
• Alcohol (7 studies)
• Cocaine (2 studies)
• Anabolic steroids (15 studies)
• Tobacco (10 studies)
• Caffeine (13 studies)

There were a total of 14,695 participants with male infertility and 23,828 control participants. The review also included additional groupings to allow for further analysis (e.g., by country, study type, substance type).

The prevalence of substance use in specific substance categories was highly dependent upon the country/region in which the study was conducted. This may be due to differences in societal and cultural factors in various areas of the world. The authors reported the following summary findings:

• Cannabis use disorder most consistently had negative impacts on sperm morphology (the shape of the sperm head, which affects its ability to fertilize eggs). However, its impact on other semen parameters was negligible.

• Although so-called “harder” drugs like heroin and cocaine may have negative impacts, there is a lack of research on these drugs and their effects on male infertility, perhaps due to their lower use prevalence compared to other “softer” drugs worldwide.

• For alcohol use disorder, the direct effects of alcohol on testosterone levels remain inconclusive. However, evidence suggests that alcohol use disorder generally has negative consequences on male fertility and results in production of semen of poorer quality. Alcohol also lowers follicle-stimulating hormone (FSH) and luteinizing hormone (LH), which significantly contribute to fertility-related processes.

• It is well known that anabolic steroids negatively contribute to male fertility, with all 15 included articles reporting either impaired semen parameters, hormonal changes, or both. These negative effects occur primarily by suppression of FSH and LH in the pituitary gland in the brain.

• The most consistent findings on tobacco’s effects on male fertility are ones specific to lower sperm counts and morphological defects.

• Caffeine has an extremely high use prevalence worldwide. Although some researchers have connected DNA damage (fragmentation) and abnormal sperm morphology to increased intakes of caffeine, these hypotheses are not likely to be true. Instead, adverse lifestyle factors (i.e., age, BMI, ejaculatory frequency, duration of sexual abstinence) in combination with high levels of caffeine intake are much more likely to contribute to factors associated with male infertility.