Researchers at the University of Hong Kong (HKU) conducted a study evaluating whether the anti-inflammatory medicine piroxicam could boost the effectiveness of the emergency contraceptive levonorgestrel. Their findings indicate a substantial gain in protection, with efficacy rising from 63% to 95% when piroxicam was used in combination with levonorgestrel. The study was published in the Lancet, a leading medical journal known for large, peer‑reviewed trials and rigorous methodology.
The clinical trial enrolled 836 women who used the emergency contraceptive pill within 72 hours after unprotected intercourse. Participants were randomly assigned to two groups: in one group, they received levonorgestrel plus a placebo; in the other group, they received levonorgestrel together with 40 mg of piroxicam, a nonsteroidal anti-inflammatory drug commonly prescribed for arthritis symptoms. This randomization ensured that any observed differences could be attributed to the addition of piroxicam rather than other factors.
Pregnancies occurred in 1 of 418 women in the piroxicam group and in 7 of the 418 women who received levonorgestrel with the placebo. Across the entire trial, there were no recorded serious adverse effects linked to the treatment regimens, suggesting the combination was well tolerated within the study’s framework and time frame.
The researchers calculated a baseline pregnancy risk of about 4.5% for women who would become pregnant after unprotected intercourse without any emergency contraception. They estimated that adding piroxicam to levonorgestrel could prevent 18 of 19 potential pregnancies (roughly 95% efficacy in this context), whereas levonorgestrel alone would prevent about 12 of 19 pregnancies (approximately 63% efficacy). These figures reflect a relative improvement attributed to the potential interaction between the two drugs and provide a quantitative measure of the additive effect observed in this trial.
Levorgestrel functions by blocking or delaying the release of luteinizing hormone, a key signal for ovulation. By disrupting this hormonal cascade, ovulation is postponed, limiting the likelihood of fertilization. Piroxicam, on the other hand, may influence prostaglandins—lipid compounds involved in multiple reproductive processes including ovulation, fertilization, and embryo implantation. The researchers propose that piroxicam might enhance contraception both before ovulation, by dampening the ovulatory signal, and after ovulation, by hindering embryo implantation, thereby offering a dual mechanism of action when used with levonorgestrel. These hypotheses were explained by study co‑author Christina Gemtsell‑Danielsson, a professor associated with the Karolinska Institute in Sweden, highlighting the potential biological pathways behind the observed efficacy improvement.
As with all clinical work, the authors noted limitations. The participant pool skewed toward women of Asian descent and with body weights under 70 kilograms, which may limit generalizability to broader populations. Additional trials have documented that body weight and body mass index can influence the effectiveness of levonorgestrel when used as an emergency measure, indicating that results may vary across different demographic and physiological profiles.
One of the study’s investigators, Dr. Raymond Lee, a researcher from HKU, commented that incorporating 40 mg of piroxicam with levonorgestrel could meaningfully enhance the protective effect of emergency contraception while maintaining a favorable safety profile. He emphasized that any consideration of this combination should be grounded in a careful assessment of individual risk and regional clinical guidelines, and that further studies would be valuable to confirm these findings in diverse populations and real‑world settings.
The broader takeaway from this research is a potential shift in how emergency contraception might be optimized in the future. If subsequent studies corroborate these results, clinicians could explore adjunctive strategies that maximize efficacy without introducing significant safety concerns. However, until such data are available across different populations and dosing scenarios, the decision to adopt piroxicam as an accompanying agent with levonorgestrel would need thoughtful evaluation by healthcare providers, taking into account individual health status, weight considerations, and potential drug interactions.