Effect of ibuprofen on semen quality

[madman]

Abstract
Ibuprofen is a widely used analgesic/antipyretic medication belongs to the nonsteroidal anti‐inflammatory class. Even though the influence of ibuprofen on semen quality has been investigated in various occasions, the comprehensive understanding and discussion of its impact on semen quality is still yet to be determined. In this work, we systematically review and reveal the effect of ibuprofen on semen quality, and thus on fertilising capability. To achieve this goal, we searched the main research databases (Scopus and PubMed) from 1 June 1986 through 13 October 2018 for English language articles and abstracts using the keywords “ibuprofen” versus “semen” and “sperm”. In addition, related published articles or abstracts were also discussed if relevant. Altogether, the main stream of research, from both in vitro and in vivo studies, presents an adverse effect of ibuprofen on different sperm parameters such as motility, viability, count and DNA integrity; however, such effect is not yet confirmed in humans. Mechanisms by which ibuprofen affects semen quality may be by reducing testosterone and prostaglandin synthesis, chelating zinc ions and inhibiting nitric oxide synthesis. However, further research studies, mainly clinical, are still of great importance to confirm the effects of ibuprofen on semen quality.






3.6 | Conclusions and future perspectives


In conclusion, the main stream of research studies (mainly in vivo system studies) demonstrates the presence of adverse effects of the use of ibuprofen, at different doses, on almost all sperm parameters such as motility, viability, count, morphology and DNA integrity. However, such effects are not yet established in humans due to the lack of research studies and research consensus. The adverse effects of ibuprofen on sperm parameters may be due to reduction in testosterone and prostaglandin synthesis, zinc‐chelating activity of ibuprofen and inhibition of nitric oxide production.

While, collectively, further research studies, mainly clinical, are still of great importance to disclose the effects of ibuprofen on semen quality and sperm physiology, and hence on the ability of fertilisation. Our laboratory is now designing a long‐term human research study to explore the effect of ibuprofen on sperm parameters, mainly sperm DNA damage

 

[Nelson Vergel]

In a 2018 study in the Proceedings of the National Academy of Sciences of the USA1, we concluded that ibuprofen alters pituitary–testis endocrine balance via selective transcriptional repression in the testis, resulting in compensated hypogonadism. This paper was discussed in a commentary by Nangia and Jensen (Ibuprofen and hypogonadism — bench to bedside to misinterpreted hype? Nat. Rev. Urol. 15, 268–269 (2018))2. Our study involved a clinical trial performed in men aged 18–35 years and exposure of adult human testes explants and a human steroidogenic cell line to ibuprofen, which is frequently used as an analgesic and often used prophylactically at high doses by athletes3,4.

In their commentary, Nangia and Jensen2 claim that the original paper argues that the class of medication to which ibuprofen belongs is the specific cause of the reduction of overall male reproductive health and male reproductive deterioration. However, this statement is contradicted by the actual content of the paper, which emphasizes that establishing the possible effect of ibuprofen on sperm production and fertility would require the design of specific experiments. Contextualization of our findings by mentioning the general concern about declining male reproductive health should not be confused with our speculations regarding the significance of our data.


The authors also asserted that our data were difficult to interpret because they were part of a larger study5. However, our data showed a consistent increase in plasma luteinizing hormone (LH) in the ibuprofen-treated group (+23% and P ≤ 0.05 after 14 days of ibuprofen; +33% and P ≤ 0.01 after 44 days of ibuprofen) compared with placebo1.
We are disappointed that Nangia and Jensen suggested that we “inadvertently provided fuel to the media fire”, thereby contributing to “misinterpreted hype”. A press release was issued by the original journal and media interest was likely fuelled by the widespread use of ibuprofen and analgesics in general. Although we requested access to media content before publication to verify their accuracy, the headlines were sometimes flashy clickbait, designed to drive traffic as is often the case in such circumstances. Other media representatives, who did not attempt to contact us, made false statements, and our study was sometimes distorted by the internet and social media.

Mild analgesics have an important medical role. However, the time has come to accept that their widespread and increasing use is not without consequences, some of which have already been identified, for example, for ibuprofen use during pregnancy or in adulthood3,6. Whether ibuprofen can have direct effects on the sperm count in young men still needs to be determined, and whether ibuprofen or other analgesics might also induce a shift from compensated hypogonadism to primary hypogonadism in ageing men7 requires particular vigilance.

Clarifying the link between ibuprofen and hypogonadism