Long-Term Ibuprofen Use Linked to Increased Risk of Male Infertility, Study Finds

Taiwan: A nationwide retrospective cohort study has highlighted a potential link between ibuprofen use and male infertility, raising important public health considerations. The findings, published in the European Journal of Obstetrics & Gynecology and Reproductive Biology, suggest that prolonged exposure to this widely used nonsteroidal anti-inflammatory drug (NSAID) may have implications for reproductive health, particularly in men of reproductive age.

“Ibuprofen use for more than 60 days was linked to a notably higher incidence of male infertility compared to acetaminophen,” the researchers wrote. 

Ibuprofen is commonly used to relieve pain, inflammation, and fever. While it is generally regarded as safe for short-term use, concerns have been raised regarding its potential impact on hormonal balance and reproductive function. Earlier research suggests that nonsteroidal anti-inflammatory drugs, including ibuprofen, may influence the male reproductive system in different ways. Considering this, Dah-Ching Ding, Department of Obstetrics and Gynecology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Foundation, Hualien, Taiwan, and colleagues sought to assess the effect of ibuprofen on male infertility in Taiwan.

For this purpose, the researchers conducted a nationwide retrospective cohort study utilizing the Taiwan National Health Insurance Database from January 1, 2000, to December 31, 2021. They focused on males aged 20–59 years who had used either ibuprofen or acetaminophen between 2000 and 2020. The primary outcome assessed was the incidence of male infertility. The researchers employed Cox regression analysis to estimate cumulative incidences and hazard ratios (HRs) with 95% confidence intervals (CIs). The Kaplan–Meier method was used to depict cumulative incidence curves. The study included 11,194 participants in both the ibuprofen and acetaminophen groups.

The study led to the following findings:

  • After propensity score matching, both groups were comparable in terms of age, medication year, and disease prevalence.
  • Using ibuprofen for more than 60 days per year was associated with a higher hazard ratio (HR: 2.01) for male infertility compared to acetaminophen use for the same duration.
  • The cumulative incidence analysis indicated a significant association between ibuprofen use for more than 60 days per year and an increased risk of male infertility compared to acetaminophen.

The researchers note that given the widespread use of ibuprofen, these findings have significant public health implications. If future prospective studies confirm this association, it could influence medical recommendations and encourage more cautious use of the drug, especially among men trying to conceive. Healthcare providers may need to discuss potential reproductive risks with patients who use ibuprofen frequently, particularly for chronic pain management.

“The link between ibuprofen use and male infertility could have important public health consequences. If future studies confirm these findings, they may influence medical guidance and shape conversations about medication use, especially for those of reproductive age,” the researchers concluded.

Reference:

Huang, W., Wang, J., & Ding, D. (2025). Ibuprofen use and male infertility: Insights from a nationwide retrospective cohort study. European Journal of Obstetrics & Gynecology and Reproductive Biology, 307, 128-133. https://doi.org/10.1016/j.ejogrb.2025.02.001

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