Ibuprofen Use Linked to Compensated Hypogonadism in Males

Ibuprofen use in young men may result in a state of compensated hypogonadism, a condition associated with impaired fertility and higher risk of cardiovascular events, according to a new study published in Proceedings of the National Academy of Sciences. 

The study – conducted by a team of researchers in Denmark and France – was placebo-controlled and recruited 31 healthy white males between the ages 18 and 35 years. The treatment group received 2 doses of ibuprofen 600mg daily for 2 weeks before and 30 days after a single exercise season.

Results showed that ibuprofen use led to an elevation of luteinizing hormone (LH) and a decreased testosterone/LH ratio, which is routinely used as a marker of testicular Leydig cell function. “The decrease in the free testosterone/LH ratio resulted primarily from the increased LH levels, revealing that testicular responsiveness to gonadotropins likely declined during the ibuprofen exposure,” the authors write. 

For short-term ibuprofen use the effects of compensated hypogonadism are reversible, however the researchers state how it is unknown whether these effects are reversible for long-term ibuprofen use.

The researchers also performed an analysis of adult testis explants to assess the direct effect of ibuprofen on the testis. Inhibition of testosterone levels was found to be significant and dose-dependent after 24 and 48 hours of ibuprofen exposure (in doses which corresponded to the oral doses used in the trial).

The authors of the study point to the wide range of endocrine disorders that may result from fluctuations in or impairment of the pituitary-gonadal axis such as infertility, depression, heart disease, arthritis and diabetes. With regard to long-term ibuprofen use, “It is also of concern that men with compensated hypogonadism may eventually progress to overt primary hypogonadism.” 

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