🌸 Primary Dysmenorrhea Prostaglandin Mechanism Simulator

Endometrial Shedding Triggers Prostaglandin Release

Falling progesterone triggers endometrial breakdown and prostaglandin release.

• Day 1: Cycle day of onset (menstruation starts)
• ~90%: Progesterone drop (luteal phase ends)
• 2–5 mm: Endometrium shed (functional layer)
• 50–90%: Women affected (some menstrual pain)

Progesterone withdrawal

Corpus luteum regresses, progesterone falls sharply.

Endometrial breakdown

Lysosomal enzymes degrade endometrial tissue rapidly.

Prostaglandin trigger

Damaged cells free arachidonic acid for synthesis.

Primary dysmenorrhea affects up to 90% of menstruating women.

COX Enzymes Convert Arachidonic Acid Into PGF2α

COX-1 and COX-2 rapidly synthesize PGF2α from membrane lipids.

• ~10×: COX-2 upregulation (secretory endometrium)
• First 48h: PGF2α peak (of menstruation)
• 3: Synthesis steps (PLA2, COX, PGF synthase)
• 3–10×: Menstrual PGF2α (higher than luteal phase)

Arachidonic acid release

Phospholipase A2 frees membrane arachidonic acid.

COX conversion

COX-1/COX-2 oxidize arachidonic acid into PGH2.

PGF2α synthase

PGH2 is converted into potent PGF2α.

Dysmenorrheic women show 3–10× higher endometrial PGF2α.

High PGF2α Drives Painful Uterine Contractions

Excess PGF2α overstimulates the myometrium, forcing strong contractions.

• ≤400 mmHg: Intrauterine pressure (vs 50–80 normal)
• >5/10min: Contraction frequency (hypercontractile pattern)
• Reduced: Uterine blood flow (ischemia occurs)
• Hours before: Pain onset (bleeding starts)

Myometrial overstimulation

PGF2α binds FP receptors, triggers calcium influx.

Ischemic pain

Sustained contractions restrict uterine blood flow.

Sensitized nerves

Ischemia and prostaglandins activate pain fibers.

Contractions can exceed 400 mmHg, cutting uterine blood supply.

Ibuprofen And Naproxen Block COX Enzyme Activity

NSAIDs competitively inhibit COX, cutting new PGF2α production.

• ~2 h: Ibuprofen half-life (dosed every 4–6h)
• 12–17 h: Naproxen half-life (longer acting)
• 30–60 min: Inhibition onset (after oral dose)
• 1–2 h: Peak plasma level (post-dose)

Competitive inhibition

NSAIDs block the COX enzyme active site.

Dose dependence

Higher doses inhibit a larger share of COX.

Pharmacokinetics

Absorption, peak, and elimination shape the effect.

Early dosing before pain peaks blocks more prostaglandin synthesis.

Suppressed PGF2α Relaxes The Uterus And Cuts Pain

Lower PGF2α reduces contraction strength and reported pain scores.

• ≤80%: Pain reduction (with adequate NSAID dosing)
• ~2–3: Number needed to treat (for pain relief)
• Within hours: Contraction normalizes (of effective dosing)
• 80–90%: Treatment success (of primary dysmenorrhea)

Contraction relaxation

Less PGF2α means weaker, less frequent contractions.

Blood flow restored

Reduced ischemia lowers pain-fiber signaling.

Clinical response

Most patients respond well to adequate dosing.

NSAIDs outperform placebo for menstrual pain in most women.