The sorption of Hydrophobic Organic Compound (HOC) onto microplastics is relatively well reported in the literature, while their desorption remains poorly investigated, and especially in biological fluids. The present study investigated the sorption and desorption of progesterone on polyethylene (PE), polypropylene (PP) and polystyrene (PS) microplastics. The sorption experiments showed that the equilibrium was reached in a few hours for all plastics. A sorption efficiency of 357.1 µg/g was found for PE and PS and 322.6µg/g for PP. Sorption experiments indicated that adsorption would happen certainly via surface sorption and potentially pore-filling mechanism. The desorption was carried out in Simulated Gastric Fluid (SGF) and Simulated Intestinal Fluid (SIF), whose formulations were more complex than similar models reported so far. It has been found that the desorption was higher in SIF compared to SGF, surely due to micelle formation in SIF promoting the pollutant solubilization. Sorption of pepsin onto microplastics has also been revealed, suggesting a competition between pollutant and pepsin for sorption sites and a potent reduction of pollutant solubilization. This study indicates that microplastics ingestion could be considered as as additional route of exposure of pollutants and therefore emphasizes pollutants bioavailability for aquatic organisms.