Effect of Medications for Gastric Acid-Related Symptoms on Total Motile Sperm Count and Concentration: A Case–Control Study in Men of Subfertile Couples from the Netherlands

INTRODUCTION: Gastric acid-related symptoms are highly prevalent in the general population (21–40%), and more than 11% of individuals use medication for the treatment of these symptoms. The uptake of micronutrients is dependent on the gastrointestinal potential of hydrogen (pH). OBJECTIVE: We hypothesized that medication affecting gastrointestinal pH reduces the availability of B vitamins, thereby deranging one-carbon metabolism and detrimentally affecting spermatogenesis. METHODS: This explorative nested case–control study in men of subfertile couples investigated associations between medication used for gastric acid-related symptoms and semen parameters. We included 40 men using medication for gastric acid-related symptoms and 843 men not using medication. Semen analyses were performed between 70 days before and 21 days after the visit. RESULTS: The use of medication was associated with a twofold higher risk of a low total motile sperm count [TMSC <1 × 10(6), odds ratio (OR) 2.090, p = 0.049] and negatively with sperm concentration (β −0.320, p = 0.028). Red blood cell folate was positively associated with TMSC (β 0.257, p = 0.026), sperm count (β 1.679, p = 0.013) and ejaculate volume (β 0.120, p = 0.023), and total homocysteine (tHcy) was negatively associated with sperm count (β −0.077, p = 0.021). CONCLUSION: Here we delineate associations between the use of medication for gastric acid-related symptoms and poor semen quality in men of subfertile couples. The use of medication for gastric acid-related symptoms is associated with a twofold higher risk of a low TMSC and a decreased sperm concentration. Although these findings warrant further research on causality, the associations between folate, tHcy and semen quality emphasize the importance of preconception counselling in male subfertility. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s40264-016-0488-8) contains supplementary material, which is available to authorized users.