Abstract
BACKGROUND: Over the years, several observational studies and case reports have been published hypothesizing a potential association between the use of proton pump inhibitors (PPIs) and sexual dysfunctions in both male and female patients. OBJECTIVES: We aimed to investigate the potential association between PPI use and sexual dysfunction onset using VigiBase, the World Health Organization international pharmacovigilance database. METHODS: All individual case safety reports of sexual dysfunctions containing PPIs (i.e. omeprazole, lansoprazole, rabeprazole, pantoprazole and esomeprazole) as suspected or interacting drugs until 4 September, 2024 were selected from VigiBase using the Standardised MedDRA Query "Sexual dysfunction". A descriptive analysis of the selected individual case safety reports was carried out. Potentially new safety signals were identified through a disproportionality analysis and calculated as a reporting odds ratio (ROR) along with a 95% confidence interval (CI), which were adjusted via Bonferroni correction for multiple testing. To account for age-related effects on sexual functions, a subgroup analysis was carried out by restricting the study population only to patients aged from 18 to 64 years. RESULTS: A total of 420,598 individual case safety reports concerning PPIs were collected in VigiBase during the study period. Of these, 841 containing at least one Preferred Term included in the "Sexual dysfunction" Standardised MedDRA Query reporting information on sex were retrieved. Overall, disproportionate reporting for omeprazole concerning erectile dysfunction (adjusted ROR, 1.76; 95% CI 1.54-2.01) was observed, while two statistically significant adjusted RORs for esomeprazole, i.e. genital discomfort (ROR, 3.66; 95% CI 1.34-10.04) and oestrogen deficiency (ROR, 3.80; 95% CI 1.03-13.99) in female patients were found. The subgroup analysis confirmed the statistically significant disproportionate reporting of erectile dysfunction for omeprazole (adjusted ROR: 1.80; 95% CI 1.49-2.16), and generated new potential safety signals including an omeprazole-induced libido decrease (adjusted ROR, 1.49; 95% CI 1.05-2.12) and esomeprazole-induced hypogonadism (adjusted ROR, 5.22; 95% CI 1.22-22.34) in male individuals, and omeprazole-induced genital discomfort (adjusted ROR, 3.55; 95% CI 1.13-11.09) in female individuals. CONCLUSIONS: Findings of this study suggest the presence of safety signals of PPI-induced sexual dysfunctions, such as erectile dysfunction, genital discomfort and oestrogen deficiency. However, further observational studies are required to validate and further characterise these potential safety signals.