Lansoprazole is a new proton-pump inhibitor that has been proven safe and effective in the treatment of gastroesophageal reflux disease (GERD) and peptic ulcer disease. In rats, the drug inhibited testosterone synthesis and was associated with Leydig cell tumours. To determine the effect of a high therapeutic dose of lansoprazole (60mg day) on male hormone levels and gonadal function, a randomised double-blind parallel study was conducted. 32 healthy volunteers participated for 8 weeks. Endocrine profiles included serum testosterone, luteinising hormone (LH), follicle-stimulating hormone (FSH), sex hormone-binding globulin (SHBG), dehydroepiandrosterone sulfate (DHEA-S), prolactin, estradiol, cortisol and thyroid function. As further evaluation of an effect on hormones, testes were monitored for changes in size and breasts for gynaecomastia. Sexual function parameters were assessed by semen analyses and a sexual function questionnaire. Testosterone levels tended to increase slightly in the lansoprazole group and decrease slightly in the placebo group. While the difference between groups was statistically significant, the magnitude of changes was small and not clinically significant. Overall, there were no clinically significant changes in hormone levels. All testicular and breast measurements remained within normal range. Similarly, no clinically significant differences between treatment groups occurred in either semen analysis or sexual-function parameters.