Stone · Drug safety 2002 · narrative review · n=?

Nonsteroidal anti-inflammatory drugs and reversible female infertility: is there a link?

Cited 71 times in the scientific literature.

Level 5 - mechanism / opinion, no new human data

Narrative review synthesizing animal mechanism studies and three clinical case series/studies

PubMed 12113640 · doi:10.2165/00002018-200225080-00001 · record verified 2026-08-26

What was done

This narrative review synthesized evidence on the relationship between nonsteroidal anti-inflammatory drug (NSAID) use and reversible female infertility. The authors evaluated the biological mechanism of cyclo-oxygenase-2 (COX-2) inhibition in ovarian follicular development, evidence from animal models (including COX-2-deficient mice and indomethacin-treated rabbits), and findings from three clinical studies in women.

What was found

The abstract reports no numerical metrics or statistical effect sizes. Mechanistically, COX-2 is active during ovarian follicular development; its inhibition leads to luteinised unruptured follicle (LUF) syndrome, where clinical signs of ovulation occur without follicular rupture or ovum release. Animal models showed that COX-2 knockout mice experienced severely impaired ovulation despite normal follicular growth, and indomethacin blocked prostaglandin-induced ovulation in rabbits. Three human studies demonstrated that NSAID administration induced delayed follicular rupture or LUF syndrome in previously ovulating women.

Why it matters

It highlights a potentially overlooked, reversible cause of female infertility related to common NSAID use, suggesting clinicians consider stopping NSAIDs before or during formal fertility workups.

Limits

The abstract reports no quantitative data, confidence intervals, dosages, specific drug classes, or patient sample sizes. Evidence in humans is drawn from only three clinical studies/case series, and systematic review methods were not employed.

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