Ibuprofen

[Michael Scally MD]

[OA] Kristensen DM, Desdoits-Lethimonier C, Mackey AL, et al. Ibuprofen alters human testicular physiology to produce a state of compensated hypogonadism. Proceedings of the National Academy of Sciences 2018. Ibuprofen alters human testicular physiology to produce a state of compensated hypogonadism

Concern has been raised over increased male reproductive disorders in the Western world, and the disruption of male endocrinology has been suggested to play a central role. Several studies have shown that mild analgesics exposure during fetal life is associated with antiandrogenic effects and congenital malformations, but the effects on the adult man remain largely unknown.

Through a clinical trial with young men exposed to ibuprofen, we show that the analgesic resulted in the clinical condition named “compensated hypogonadism," a condition prevalent among elderly men and associated with reproductive and physical disorders. In the men, luteinizing hormone (LH) and ibuprofen plasma levels were positively correlated, and the testosterone/LH ratio decreased.

Using adult testis explants exposed or not exposed to ibuprofen, we demonstrate that the endocrine capabilities from testicular Leydig and Sertoli cells, including testosterone production, were suppressed through transcriptional repression. This effect was also observed in a human steroidogenic cell line. Our data demonstrate that ibuprofen alters the endocrine system via selective transcriptional repression in the human testes, thereby inducing compensated hypogonadism.

 

[Johnny442]

So what does this mean for someone like myself that suffers from an inflammatory disease and has to take anti inflammatories daily? I’m already on trt, by the way.

 

[Oregongearhead]

So what does this mean for someone like myself that suffers from an inflammatory disease and has to take anti inflammatories daily? I’m already on trt, by the way.

...And those of us on low dose (81mg) aspirin ? Same effect ?

 

[thrombus]

I wonder how much Ibuprofen is required to lower testosterone levels enough to qualify for TRT.

 

[Michael Scally MD]

Nangia AK, Jensen D. Ibuprofen and hypogonadism — bench to bedside to misinterpreted hype? Nature Reviews Urology 2018. http://dx.doi.org/10.1038/nrurol.2018.26

A recent study suggests modulation of luteinizing hormone signalling within the hypothalamic–pituitary–gonadal axis and downstream transcriptional effects caused by sustained ibuprofen use. However, this study cannot be used to draw any clinical conclusions regarding effects of ibuprofen on male androgenic or reproductive health. Thus, the andrological effects of its use remain unclear and would benefit from further investigation.

…

Although the merit of this and any work should be judged solely on the scientific evidence presented with critical peer review, the consequence of media coverage of this study and claims about the potential long-term significance of the findings to the nonmedical and even medical community at large are hard to ignore.

The effect created from the self-perpetuating and sensational social and mainstream media coverage and fervour over this study, without careful review of the evidence it contained, has possibly led to the misrepresentation of the findings and the incorrect suggestion that ibuprofen affects male reproductive health and lowers testosterone levels.

As such, the authors have provided some evidence to this effect and have highlighted the issue, but might have inadvertently provided fuel to the media fire with their statement. Whether the short term or chronic, sustained use of ibuprofen is detrimental to reproductive health at this time is unclear.

Determination of the male androgenic and reproductive health effects of this very commonly used class of medication still requires further robust clinical investigation before making such bold significance statements that can be generalized and quoted out of context from the evidence.

 

[Michael Scally MD]

Analgesic and Anti-Inflammatory Drugs in Sports: Implications for Exercise Performance and Training Adaptations

Over-the-counter analgesics, such as anti-inflammatory drugs (NSAIDs) and paracetamol, are widely consumed by athletes worldwide to increase pain tolerance, or dampen pain and reduce inflammation from injuries. Given that these drugs also can modulate tissue protein turnover, it is important to scrutinize the implications of acute and chronic use of these drugs in relation to exercise performance and the development of long-term training adaptations.

In this review we aim to provide an overview of the studies investigating the effects of analgesic drugs on exercise performance and training adaptations relevant for athletic development. There is emerging evidence that paracetamol might acutely improve important endurance parameters as well as aspects of neuromuscular performance, possibly through increased pain tolerance. Both NSAIDs and paracetamol have been demonstrated to inhibit cyclooxygenase (COX) activity, which might explain the reduced anabolic response to acute exercise bouts.

Consistent with this, NSAIDs have been reported to interfere with muscle hypertrophy and strength gains in response to chronic resistance training in young individuals. Although it remains to be established whether any of these observations also translate into detriments in sport-specific performance or reduced training adaptations in elite athletes, the extensive use of these drugs certainly raises practical, ethical and important safety concerns that need to be adressed.

Overall, we encourage greater awareness among athletes, coaches and support staff on the potential adverse effects of these drugs. A risk-benefit analysis and professional guidance is strongly advised before the athlete considers analgesic medicine for training or competition.

Lundberg TR, Howatson G. Analgesic and anti-inflammatory drugs in sports: implications for exercise performance and training adaptations. Scandinavian journal of medicine & science in sports 2018;0. https://doi.org/10.1111/sms.13275

 

[Sparkyp]

great. i'm prescribed 600mg 3X a day with colchicine for my pericarditis. last time the ibuprofen knocked this flare up out in a couple weeks.

 

[Michael Scally MD]

Effect of Ibuprofen on Semen Quality

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.

Banihani SA. Effect of ibuprofen on semen quality. Andrologia 2019. https://doi.org/10.1111/and.13228

 

[Michael Scally MD]

[OA] Clarifying the Link Between Ibuprofen and Hypogonadism

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.

Jégou B, Kristensen DM. Clarifying the link between ibuprofen and hypogonadism. Nat Rev Urol. 2019;16(3):201. Clarifying the link between ibuprofen and hypogonadism

 

[Villain]

So what does this mean for someone like myself that suffers from an inflammatory disease and has to take anti inflammatories daily? I’m already on trt, by the way.

Have you considered natural anti-inflammatories like ginger and turmeric?