Ibuprofen is considered one of the safest over-the-counter pain relievers. But the effects of the drug may be causing a testosterone problem called “compensated hypogonadism” that causes reproductive and general health problems, according to a new study in the Proceedings of the National Academy of Sciences.

“The study shows that ibuprofen use results in selective transcriptional repression of endocrine cells in the human testis,” write the European scientists. “This repression results in the elevation of the stimulatory pituitary hormones, resulting in a state of compensated hypogonadism, a disorder associated with adverse reproductive and physical health disorders.”

The experiments involved a randomized, controlled trial, an ex vivo observation of the drugs’ effects on testicles, and an in vitro look at a human cell line.

The 31 young men, aged 18 to 35, were split into groups for the double-blinded trial.  Seventeen received a placebo and 14 were administered ibuprofen both two weeks before and 30 days after a single exercise session, according to the study.

The results were clear, they report.

“We found an 18 percent decrease in the ibuprofen group compared with the placebo group after 14 days and a 23 percent decrease after 44 days,” they write.

The adult testis explants were taken from donors who had prostate cancer, they write. The in vitro models were measured using human adrenocortical carcinoma cell lines, they add. Together, the laboratory work showed that the ibuprofen was impacting an RNA pathway.

“Measuring the mRNA expression of genes involved in steroidogenesis in vitro showed that ibuprofen had a profound inhibitory effect on the expression of these genes, consistent with that seen above in our ex vivo organ model,” they write. “Taken together, these data examining effects on the endocrine cells confirm that ibuprofen-induced changes in the transcriptional machinery were the likely reason for the inhibition of steroidogenesis.”

Previous research has indicated that ibuprofen can cause birth defects. However, a study in November by Ohio State University scientists indicated that the drug may actually block some damage from fetal alcohol exposure.