(801) Exploring the Association Between Cannabis Use and Testicular Dysfunction: A Systematic Review and Meta-Analysis

Introduction Cannabis is the most widely used psychoactive substance globally, its main compound, tetrahydrocannabinol (THC), acts on the endocannabinoid system (ECS), which regulates key reproductive processes such as spermatogenesis, sperm motility, and fertilization. Given the increasing prevalence of cannabis use and the heterogeneity of current evidence, a systematic review and meta-analysis are needed to clarify its potential impact on male reproductive parameters. Objective Evaluate the association between cannabis use and male reproductive function, specifically spermatic parameters and serum hormone levels. Methods PubMed, Embase, and Cochrane Library databases were systematically searched using MeSH/Emtree terms and free-text keywords related to cannabis, THC, fertility, semen, and hormones. When studies reported medians or confidence intervals only, data were converted to means and standard deviations using formulas by Luo et al., Wan et al., and Maldonado-Fernandez. A random-effects model was employed to compute mean differences. Heterogeneity was evaluated using the I2 and Q statistics, and publication bias was assessed through funnel plots and Egger’s test. Sensitivity analyses were performed by excluding high-risk or outlier studies. All statistical analyses were conducted using R software version 4.4.1. Results were reported according to the PRISMA statement guidelines. This study was registered in PROSPERO (CRD420251132635). Results Total of 18 studies comprising 5,766 patients and 6,231 samples for sperm outcome with age 28.8 ± 7.3 years and 21,066 patients with age 36.5 ± 9.9 years for hormonal results were included in this analysis. All cannabis users in the studies reported smoking greater than 1 joint per week in the previous months. Pooled analysis showed significant reduction in morphology among cannabis users (MD = –1.02; CI 95%: –1.93 to –0.10; p < 0.05), favoring non-users. When restricted to studies strictly following WHO criteria remained, this finding was still the only notable one. No differences were observed for sperm concentration (MD = -0.91; CI 95%: -6.12 to 4.30; p = 0.73), ejaculation volume (MD = -0.23; 95% CI: -0.50 to 0.05; p = 0.1034), total sperm count (MD = -13.01; CI 95%: -34.64 to 8.61; p = 0.23), progressive motility (MD = 0.41; CI 95% -1.37 to 2.18; p = 0.65) or motility (MD = -1.99; CI 95%: -5.49 to 1.52; p = 0.26). Among hormonal parameters, testosterone (MD = 0.84; CI 95%: -0.61 to 2.30; p = 0.25), FSH (MD = -0.38; CI 95%: -1.59 to 0.82; p = 0.53) and LH (MD = -0.01; CI 95%: -0.27 to 0.26; p = 0.94) levels were comparable between groups, while SHBG was significantly higher among cannabis users, favoring the THC group (MD = 3.90; 95% CI: 1.67 to 6.13; p < 0.05). Initial heterogeneity for morphology (I2 = 65%) dropped to 0% after excluding the outlier study (Amor et al., 2025), with results remaining significant (MD = –0.68; 95% CI: –0.99 to –0.37; p < 0.05). Conclusions Cannabis use was associated with lower normal sperm morphology, even after sensitivity and heterogeneity analyses, while no significant differences were observed for other seminal parameters. Regarding hormonal outcomes, cannabis users presented higher SHBG levels compared to non-users. Disclosure No