Nonsteroidal antiinflammatory drug resistance in dysmenorrhea: epidemiology, causes, and treatment

Am J Obstet Gynecol. 2018 Apr;218(4):390-400. doi: 10.1016/j.ajog.2017.08.108. Epub 2017 Sep 6.


Although nonsteroidal antiinflammatory drugs can alleviate menstrual pain, about 18% of women with dysmenorrhea are unresponsive, leaving them and their physicians to pursue less well-studied strategies. The goal of this review is to provide a background for treating menstrual pain when first-line options fail. Research on menstrual pain and failure of similar drugs in the antiplatelet category suggested potential mechanisms underlying nonsteroidal antiinflammatory drug resistance. Based on these mechanisms, alternative options may be helpful for refractory cases. This review also identifies key pathways in need of further study to optimize menstrual pain treatment.

Keywords: adenomyosis; endometriosis; menstrual pain; nonsteroidal antiinflammatory drugs; oral contraception; primary dysmenorrhea; secondary dysmenorrhea.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Ablation Techniques
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects*
  • Antidiuretic Hormone Receptor Antagonists / therapeutic use
  • Aromatase Inhibitors / therapeutic use
  • Calcium Channel Blockers / therapeutic use
  • Complementary Therapies
  • Contraceptives, Oral, Hormonal / therapeutic use
  • Denervation
  • Drug Resistance*
  • Dysmenorrhea / epidemiology
  • Dysmenorrhea / etiology
  • Dysmenorrhea / therapy*
  • Female
  • Gonadotropin-Releasing Hormone / agonists
  • Humans
  • Medication Adherence
  • Parasympatholytics / therapeutic use
  • Pharmacogenomic Variants
  • Receptors, Oxytocin / antagonists & inhibitors
  • Sildenafil Citrate / therapeutic use
  • Uterus / innervation
  • Vasodilator Agents / therapeutic use


  • Anti-Inflammatory Agents, Non-Steroidal
  • Antidiuretic Hormone Receptor Antagonists
  • Aromatase Inhibitors
  • Calcium Channel Blockers
  • Contraceptives, Oral, Hormonal
  • Parasympatholytics
  • Receptors, Oxytocin
  • Vasodilator Agents
  • Gonadotropin-Releasing Hormone
  • Sildenafil Citrate