Mechanism of Action: NSAIDs in Controlling Abnormal Uterine Bleeding
NSAIDs reduce abnormal uterine bleeding by 25-50% through inhibition of prostaglandin synthesis in the endometrium, which decreases both menstrual blood flow and associated dysmenorrhea. 1, 2, 3
How NSAIDs Work at the Molecular Level
NSAIDs control AUB through a specific endometrial mechanism:
Prostaglandin inhibition: NSAIDs block cyclooxygenase enzymes, reducing prostaglandin E2 and F2-alpha production in the endometrium, which are elevated in women with heavy menstrual bleeding 4, 3
Vasoconstriction effect: Decreased prostaglandin levels lead to increased endometrial vasoconstriction and reduced blood flow during menstruation 3
Hemostatic improvement: The altered prostaglandin balance favors platelet aggregation and local hemostasis within the endometrial vasculature 4
Clinical Efficacy Data
The reduction in menstrual blood loss is clinically significant but modest:
- Expected reduction: 30-50% decrease in menstrual blood volume compared to placebo 5, 4
- Pain control: Simultaneous improvement in dysmenorrhea through the same prostaglandin-blocking mechanism 2, 3
- Comparative effectiveness: NSAIDs are less effective than tranexamic acid (40-60% reduction), levonorgestrel IUD (65-85% reduction), or combined oral contraceptives (40-50% reduction) 5, 4, 3
Position in Treatment Algorithm
NSAIDs are recommended as first-line therapy for AUB, particularly when hormonal contraception is contraindicated or the patient desires immediate fertility. 1, 5
- Optimal candidates: Women with ovulatory dysfunctional uterine bleeding who need non-hormonal management 5, 6
- Treatment duration: Short-term use for 5-7 days during menstruation is typically sufficient 2
- Preferred agents: Mefenamic acid, flufenamic acid, and indomethacin have demonstrated efficacy, with naproxen and ibuprofen preferred for patients with cardiovascular risk factors 2
Critical Safety Considerations and Contraindications
NSAIDs should generally be avoided in women with spontaneous coronary artery dissection (SCAD) or significant cardiovascular disease due to their association with myocardial infarction and thrombosis. 7
- Cardiovascular caution: Use with extreme caution in patients with known cardiovascular disease, as NSAIDs carry thrombotic risk 7, 2
- Gastrointestinal risk: Avoid in patients with peptic ulcer disease history, advanced age (>60 years), or concurrent corticosteroid therapy 2
- Antiplatelet interaction: In women on dual antiplatelet therapy (such as post-SCAD patients), NSAIDs are contraindicated as they compound bleeding risk while paradoxically increasing thrombotic risk 7
When NSAIDs Are Insufficient
If NSAIDs fail to adequately control bleeding after 3 menstrual cycles:
- Next step: Progress to tranexamic acid (non-hormonal alternative with superior efficacy) or levonorgestrel IUD if contraception is acceptable 1, 5
- Combination therapy: NSAIDs may be combined with other agents, though this approach requires careful monitoring 6
- Surgical consideration: For refractory cases in women not desiring future fertility, endometrial ablation techniques provide superior long-term efficacy compared to continued medical management 5