Can NSAIDs Use Reduce Testosterone?

Welcome to Chi-research. A weekly publication by ProCredits reviewing current research associated with the Chiropractic profession. In this week’s edition, we are reviewing a 2018 article looking at the effects of NSAIDs on testosterone production and testicular physiology.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

Nonsteroidal anti-inflammatory drugs or NSAIDs, which include aspirin, ibuprofen, and naproxen just to name a few, are among the most used drugs worldwide with effective therapeutic properties. It is estimated that more than thirty million people use NSAIDs every day, and they account for 60% of the US over-the-counter analgesic market. However, it is well known that they are associated with gastrointestinal adverse events, kidney impairment, accelerated articular cartilage degeneration, and, according to a 2018 study[1], are found to induce a state of “compensated hypogonadism” in males.

This is a condition where men have normal levels of testosterone but higher levels of luteinizing hormone (LH). To put it simply, normally when the body wants to produce testosterone, LH is released from the pituitary gland and stimulates the Leydig cells of the testes to produce testosterone. However, this study found that when consuming NSAIDs, the testes do not respond to LH the same way and more LH is needed to be released for the testes to produce the same amount of testosterone.

This may be a long-term problem because “conditional hypogonadism” will lead to “real hypogonadism” in which the testes will not keep up with the high levels of LH over time and will then produce less testosterone. Plus, since LH also stimulates the Sertoli cells, which are critical to sperm production, it was found that regular use of NSAIDs causes diminished sperm production leading to infertility.

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. Birthing statistics show that the US birth rate has fallen over 30% from 1991 to 2021 correlating with increased NSAID use.

Also, it has been well known through several studies that mild analgesic exposure during fetal life is associated with antiandrogenic effects and congenital malformations, but the effects on the adult man remained largely unknown until this study. In fact, the researchers stated that the striking dual effect of ibuprofen on Leydig and Sertoli cells suggests that ibuprofen, of all the chemical classes considered, has “the broadest endocrine-disturbing properties identified so far in men.”

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[1] Kristensen DM, et al. Ibuprofen alters human testicular physiology to produce a state of compensated hypogonadism. Proc Natl Acad Sci USA. 2018 Jan 23;115.