Use of paracetamol (acetaminophen) as a non-prescription analgesic and semen quality in young men - a cross-sectional study.

BACKGROUND Paracetamol (acetaminophen) is a frequently used non-prescription analgesic with suggested endocrine disrupting properties. Epidemiological evidence on the effect of paracetamol on male fecundity is sparse. OBJECTIVES To investigate if use of paracetamol as an oral non-prescription mild analgesic was associated with semen quality in young men. MATERIALS AND METHODS This cross-sectional study was based on data from the Fetal Programming of Semen Quality (FEPOS; 2017-2019) cohort of 1,058 young men (18-21 years) included in the Danish National Birth Cohort. Participants completed a comprehensive online questionnaire on health behavior including analgesic use and provided a semen sample. Negative binomial regression models were used to estimate the percentage differences (adjusted mean ratios (aMR)) in semen quality characteristics according to paracetamol use (no; yes) and frequency of use (Almost never; <1/month; ≥1/month; ≥1/week). RESULTS In total, 28% of the 913 participants with available data reported use of paracetamol within the last six months. We found a slightly higher total sperm count (aMR 1.13 95% CI (0.99;1.30)) in users compared to non-users but other semen characteristics were unaffected. The frequency of use was suggestive of lower total sperm count and morphologically normal sperm cells primarily among users ≥1/week, however, CIs were wide. DISCUSSION We were unable to account for the underlying reason for paracetamol use, which may induce confounding by indication. Exposure misclassification due to recall is likely but probably non-differential due to the participants' young age and unawareness of semen quality. Due to the rapid plasma half-life of paracetamol and few frequent users, it was not possible to conclude on potential high-dose effects. CONCLUSION Our findings do not suggest any strong detrimental effect of paracetamol use on semen quality within this sample of young Danish men. However, effects of high-dose and frequent use cannot be excluded. This article is protected by copyright. All rights reserved.