Marijuana smoking and markers of testicular function among men from a fertility centre.

study questionIs marijuana smoking associated with semen quality, sperm DNA integrity or serum concentrations of reproductive hormones among subfertile men? SUMMARY ANSWER: Men who had ever smoked marijuana had higher sperm concentration and count and lower serum FSH concentrations than men who had never smoked marijuana; no differences were observed between current and past marijuana smokers. WHAT IS KNOWN ALREADY: Studies of marijuana abuse in humans and animal models of exposure to marijuana suggest that marijuana smoking adversely impacts spermatogenesis. Data is less clear for moderate consumption levels and multiple studies have found higher serum testosterone concentrations among marijuana consumers. STUDY DESIGN, SIZE, DURATION: This longitudinal study included 662 subfertile men enroled at the Massachusetts General Hospital Fertility Center between 2000 and 2017. The men provided a total of 1143 semen samples; 317 men also provided blood samples in which we measured reproductive hormones. PARTICIPANTS/MATERIALS, SETTING,

methodsUse of marijuana and other drugs was self-reported at baseline. Standard protocols were followed for measuring semen quality, sex hormones and DNA integrity. We used linear mixed effect models with a random intercept to evaluate the associations of self-reported marijuana smoking at enrolment with semen parameters from subsequently collected samples, and linear regression models for sperm DNA integrity and serum reproductive hormones, while adjusting for confounders including smoking and cocaine use. MAIN RESULTS AND THE ROLE OF CHANCE: Men who had ever smoked marijuana (N = 365) had significantly higher sperm concentration (62.7 (95% confidence interval: 56.0, 70.3) million/mL) than men who had never smoked marijuana (N = 297) (45.4 (38.6, 53.3) million/mL) after adjusting for potential confounders (P = 0.0003). There were no significant differences in sperm concentration between current (N = 74) (59.5 (47.3, 74.8) million/mL) and past marijuana smokers (N = 291) (63.5 (56.1, 72.0) million/mL; P = 0.60). A similar pattern was observed for total sperm count. Furthermore, the adjusted prevalence of sperm concentration and total sperm motility below WHO reference values among marijuana smokers was less than half that of never marijuana smokers. Marijuana smokers had significantly lower follicle stimulating hormone (FSH) concentrations than never marijuana smokers (-16% (-27%, -4%)) and there were no significant differences between current and past marijuana smokers (P = 0.53). Marijuana smoking was not associated with other semen parameters, with markers of sperm DNA integrity or with reproductive hormones other than FSH. Chance findings cannot be excluded due to the multiple comparisons. LIMITATIONS, REASONS FOR CAUTION: Our results may not be generalisable to men from the general population. Marijuana smoking was self-reported and there may be misclassification of the exposure. WIDER IMPLICATIONS OF THE

findingsThese findings are not consistent with a deleterious effect of marijuana on testicular function. Whether these findings are reflective of the previously described role of the endocannabinoid system in spermatogenesis or a spurious association requires confirmation in further studies. STUDY FUNDING/COMPETING INTEREST(S): The project was funded by grants R01ES009718 and P30ES000002 from the National Institute of Environmental Health Sciences (NIEHS). None of the authors has any conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.