Ibuprofen use may compromise reproductive health in men

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Increased ibuprofen administration elevates LH and decreases testosterone to LH and inhibin B to FSH ratios in young adult men.
Increased ibuprofen administration elevates LH and decreases testosterone to LH and inhibin B to FSH ratios in young adult men.

Ibuprofen induces compensated hypogonadism, compromising the endocrine system through selective transcriptional repression in testes, according to a small study published in Proceedings of the National Academy of Sciences.

David Møbjerg Kristensen, PhD, of the Department of Neurology at the University of Copenhagen, and associates conducted a series of trials comparing the effects of ibuprofen with pituitary-gonadal feedback.

Thirty-one white males (aged 18 to 35) in an in vivo, double-blinded, placebo-controlled trial were randomly administered either ibuprofen or a placebo for 2 weeks before and 30 days following one exercise session. Average plasma ibuprofen concentrations varied between 25 and 35 μg/mL with the highest measured concentration at 100 μg/mL (600-mg administration).

In a separate, ex vivo observation, testes from prostate cancer patients, who had not experienced any antihormonal treatment, were used to assess the effects of ibuprofen on testis physiology.

Using in vitro testing, the investigators analyzed the effects of ibuprofen on adult testis explants from donors, which were in sync to concentrations administered during in vivo testing. Some explants were exposed to ibuprofen to illustrate the endocrine proficiencies of Leydig and Sertoli cells, measured through inhibin B and anti-Müllerian hormone (AMH) secretions.          

Total testosterone and its immediate downstream metabolic product, 17β-estradiol, levels were analyzed using sex-hormone binding globulin (SHBG).

The researchers found that neither free testosterone nor SHBG levels were influenced by ibuprofen immediately, but testosterone concentration was significantly inhibited by ibuprofen based on dosage. After 24 and 48 hours, there was a -40% amplification (β=-0.405 at 24 h and β=-0.664 at 48 h). All steroids from pregnenolone to testosterone and 17β-estradiol were inhibited.

Negative effects of ibuprofen on Sertoli cells indicated an inverse relation between increased ibuprofen doses and inhibin B after 24 h (β=-0.467), resulting in AMH inhibition (in vivo and ex vivo) and the reduced ratio of inhibin B to follicle stimulating hormone (FSH). Ibuprofen concentrations of 10-7 M to 10-4 M significantly reduced inhibin B production (β=-0.739), and, though not significant, AMH production was also reduced (β=-04.51). Changes in FSH concentration were negligible, but a positive relationship was observed between ibuprofen and luteinizing hormone (LH). LH concentrations increased by 23% at day 14 and by 33% at day 44, decreasing the ratio of testosterone to LH.

“Ibuprofen displayed broad transcription-repression abilities involving steroidogenesis, peptide hormones, and prostaglandin synthesis,” stated the authors. “Men with compensated hypogonadism may eventually progress to overt primary hypogonadism, which is characterized by low circulating testosterone and prevalent symptoms including reduced libido, reduced muscle mass and strength, and depressed mood and fatigue.”

Reference

  1. Kristensen DM, Desdoits-Lethimonier C, Mackey A, et al. Ibuprofin alters human testicular physiology to produce a state of compensated hypogonadism. PNAS. 2018 Jan 8.  doi: 10.1073/pnas.1715035115
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