Effect of methylphenidate on the onset of puberty and reproductive organ development in rats

Methylphenidate (MPH) is the first-line therapy for attention deficit hyperactivity disorder (ADHD) in children and adolescents. The aim of this study was to investigate the effects chronic MPH administration on reproductive parameters in both male and female pre-pubertal rats and reversibility of these effects. Sprague-Dawley rats were administered with 5 mg/kg MPH or saline orally from postnatal day (PND) 21 to PND60 and from PND21 to PND90. In addition, recovery groups from both sexes, in which MPH administration was stopped from PND60 to PND90 were included. Puberty onset, serum luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone and estradiol levels were determined. Histopathology of male and female reproductive organs was examined. Puberty onset was significantly early in the males (p<0.01), but late in females (p<0.05). In males, serum LH and FSH levels were similar. Testosterone levels tended to decrease in MPH-treated animals. Morphology of testes, epididymis and vas deferens was disrupted in MPH-treated animals, while it was improved in the recovery group. In females, estradiol levels decreased in MPH-treated group compared to controls, and elevated LH levels were detected in recovery group. Similar to the males, disruption in the reproductive organ histology was seen with morphological deterioration in basement membrane of the ovaries of MPH-treated groups. These adverse effects of MPH were recovered after drug cessation for 30 days. The present results demonstrate that MPH could affect the reproductive functions in both male and female rats. However, our findings also suggest that those effects are transient.