The article implies to use sparingly and carefully, I think I’ll just stick with aspirin…
Ibuprofen alters human testicular physiology to produce a state of compensated hypogonadism
Hypo= little or too little
gonadism= state of The Boys
hypogonadism= ~ tiny balls or ineffective naughty bits
Concern has been raised over declining male reproductive health in humans. Our study addresses this issue by extending data showing antiandrogen effects of analgesics and suggests that such compounds may be involved in adult male reproductive problems. Using a unique combination of a randomized, controlled clinical trial and ex vivo and in vitro approaches, we report a univocal depression of important aspects of testicular function, including testosterone production, after use of over-the-counter ibuprofen. The study shows that ibuprofen use results in selective transcriptional repression of endocrine cells in the human testis. 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.
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.
So looks like the ladies need to avoid such NSAIDS during pregnancy or they run a higher risk of Nancy Boys…
Much concern has been raised over declining male reproductive health, and the disruption of male endocrinology has been suggested to play a central role (1, 2). Male reproduction and general health rely on androgens, as well as on other hormones, which are mainly produced by testicular Leydig and Sertoli cells. In addition to the testis, the androgens act in many somatic organs, e.g., producing anabolic effects on muscle mass and influencing cognitive functions (3). Luteinizing hormone (LH) produced by the pituitary is the primary stimulator of testosterone production, and the testosterone/LH ratio is routinely used as a clinical marker of Leydig cell function. When Leydig cell function is compromised, normal or nearly normal testosterone levels can often be sustained by augmented LH levels, as observed in the clinical entity termed “compensated hypogonadism” (4). The essential importance of the pituitary–gonadal axis is emphasized by the recent association of hypogonadism with a wide range of risk factors and all-cause mortality in men (4, 5).
The so-called “over-the-counter” mild analgesics (hereafter simply called “analgesics”), such as acetaminophen/paracetamol, acetylsalicylic acid/aspirin, and ibuprofen, are among the most commonly used pharmaceutical compounds worldwide (6, 7). Increasing evidence from recent years shows that exposure to analgesics can generate negative endocrine and reproductive effects during fetal life (6). Nonetheless, no in-depth studies have analyzed the effect of mild analgesics on the human pituitary–gonadal axis. In this context, ibuprofen is especially interesting because of its increasing use in the general population and in particular by elite athletes (8⇓⇓⇓–12).
Therefore in this study we focused on how ibuprofen, used in the general population for aches, pains, fever, and arthritis and heavily used by athletes (13), affects the pituitary–testis axis. Because of the intrinsic great challenge in identifying endocrine-disrupting effects of chemicals in the adult human, we performed a unique combination of three interconnected approaches: (i) a randomized, controlled clinical trial; (ii) an ex vivo organ model using adult human testis explants; and (iii) a standardized in vitro model system based on a steroidogenic cell line of human origin to complement the ex vivo approach. The complementary results revealed that ibuprofen induces a state of compensated hypogonadism by modifying hormonal profiles through selective repression of gene expression.
Ibuprofen Affects the Hormonal Balance in Adult Men.
We conducted a randomized, controlled clinical trial of ibuprofen administration to identify its possible effects on pituitary–gonadal feedback in young men. During administration, ibuprofen levels in plasma ranged on average from 25 to 35 µg/mL (∼1.2–1.7 × 10−4 M); the highest level measured was 100 µg/mL (4.85 × 10−4 M). The mean of this ibuprofen concentration was in the range measured after administration of 600 mg of ibuprofen to healthy volunteers (14). Samples drawn before administration showed that there were no initial differences between the placebo and ibuprofen groups for hormones or sex hormone-binding globulin (SHBG), a liver protein that specifically binds a substantial part of circulating testosterone (Fig. S1).
We investigated the levels of total testosterone and its direct downstream metabolic product, 17β-estradiol. Administration of ibuprofen did not result in any significant changes in the levels of these two steroid hormones after 14 d or at the last day of administration at 44 d (Fig. 1 A and C). The levels of free testosterone were subsequently analyzed by using the SHBG levels. Neither free testosterone nor SHBG levels were affected by ibuprofen during the administration (Fig. 1 A and C).
Ibuprofen Inhibits Steroidogenesis ex Vivo and in Vitro.
To determine the direct effect of ibuprofen on the testis, we next exposed adult testis explants from donors to doses of 10−9–10−4 M, which corresponded to the oral doses producing mean plasma levels of 1.2–1.7 × 10−4 M used among the men in the trial (see above). We first investigated testosterone production after 24 and 48 h of ibuprofen exposure to assess its effects on Leydig cell steroidogenesis. Inhibition of testosterone levels was significant and dose-dependent (β = −0.405, P = 0.01 at 24 h and β = −0.664, P < 0.0001 at 48 h) (Fig. 2A) and was augmented over time (10−4 M at 24 h and 10−5–10−4 M at 48 h, −40%) (Fig. 2A). Examination of the effect of ibuprofen exposure on both the ∆4 and ∆5 steroid pathways (Fig. 2B) showed that it generally inhibited all steroids from pregnenolone down to testosterone and 17β-estradiol; the production of each steroid measured decreased at doses of 10−5–10−4 M. Under control conditions, production of androstenediol and dehydroepiandrosterone (DHEA) was below the limit of detection except in one experiment with DHEA (Fig. 2B).
And a lot more. In short, this stuff messes up how The Boys work.