12-phase flow (12)

1. 1FRAME
   Primary (prostaglandin-mediated, no pathology) vs secondary (endometriosis commonest) dysmenorrhoea. Clinical ± imaging diagnosis is acceptable and EMPIRIC medical treatment may begin WITHOUT mandatory laparoscopy (ESHRE 2022 Becker PMID 35350465; ACOG CO 760 PMID 30461694)
   inputs: age, menarche_to_pain_onset_interval
   advance: primary-vs-secondary frame set; empiric-treatment-without-laparoscopy paradigm acknowledged
2. 2ENTRY
   Recurrent menses-locked crampy pelvic pain in a reproductive-age woman or adolescent; recognise the endometriosis-suggestive cluster early to shorten the 6.4-yr diagnostic delay (Brandes 2022 PMID 36514039; Horne BMJ 2022 PMID 36375827)
   inputs: age
   advance: entry trigger present
3. 3CONTEXT
   Menarche-to-onset interval, cyclicity drift, deep dyspareunia, dyschezia/cyclical bladder-bowel symptoms, subfertility, family history, PID/STI, prior cervical procedure (stenosis), IUD type/timing, US-MEC comorbidity inventory, NSAID GI/renal/CV risk (ESHRE 2022; ACOG CO 760; SOGC 437 2023)
   inputs: menarche_to_pain_onset_interval, pain_cyclicity_drift, us_mec_comorbidity_inventory
   advance: primary-vs-secondary phenotype matrix + US-MEC eligibility prelim captured
4. 4RED_FLAGS
   Adolescent never-pain-free cyclical pain + pelvic mass ± primary amenorrhoea → obstructive Müllerian/outflow anomaly (gynae emergency — risk of haematometra/retrograde seeding); acute severe unilateral pain (torsion / ruptured endometrioma → route to gyn.ovarian-torsion.v1); fever + pelvic pain (PID → gyn.pelvic-inflammatory-disease.core.v1); pregnancy-related pain (ectopic) (ACOG CO 760; ESHRE 2022)
   inputs: pregnancy_status
   advance: obstructive anomaly / torsion / PID / ectopic screened and routed if present
5. 5INITIAL_WORKUP
   Targeted history + pelvic/bimanual exam (defer or external-only if virginal adolescent — diagnosis remains clinical), urine/serum β-hCG, STI NAAT if risk, CBC + inflammatory markers if heavy bleeding or PID suspicion; imaging NOT required for a primary-pattern presentation (ACOG CO 760; ESHRE 2022; CDC STI 2021)
   inputs: pregnancy_status, nsaid_gi_renal_cv_risk
   actions: workup.dysmenorrhea, panel.cbc, panel.inflammation
   advance: pregnancy excluded; primary-pattern → empiric treatment; secondary features → branching imaging
6. 6BRANCHING_WORKUP
   Transvaginal ultrasound first-line when secondary suspected / red flag / empiric-trial failure (endometrioma SpPin Se 0.93/Sp 0.96; DIE Se 0.79/Sp 0.94 — Nisenblat 2016 PMID 26919512); MRI for DIE mapping or Müllerian anomaly (DIE Se 0.94; eMRI Se ~92% — Avery 2024 PMID 38110143); gynae/endometriosis-centre ± laparoscopy only if imaging-negative with persistent high suspicion and a fertility/surgical question (ESHRE 2022 — laparoscopy NOT a precondition for empiric medical therapy)
   inputs: transvaginal_ultrasound, pelvic_mri
   actions: workup.dysmenorrhea
   advance: imaging done OR explicitly deferred in favour of empiric trial; surgical-referral decision made
7. 7DIFFERENTIAL
   MECE: primary vs endometriosis vs adenomyosis vs leiomyoma/fibroid vs PID-sequela vs cervical-stenosis vs obstructive Müllerian/outflow anomaly vs ovarian (endometrioma/recurrent cyst) vs IUD-related; non-gyn mimics — IBS, interstitial cystitis/BPS, pelvic-floor myalgia, MSK (ESHRE 2022; SOGC 437 2023; Horne BMJ 2022)
   inputs: pain_cyclicity_drift, deep_dyspareunia
   advance: terminal diagnosis assigned or empiric-treat-and-reassess pathway opened
8. 8RISK_STRATIFICATION
   Endometriosis-suggestive feature count + family history + onset timing → endometriosis posterior; fertility intent; central-sensitisation / chronic-pelvic-pain overlap; US-MEC eligibility tier driving hormonal selection (ESHRE 2022; ACOG CO 760; calc.us_mec)
   inputs: us_mec_comorbidity_inventory, subfertility
   actions: calc.us_mec
   advance: endometriosis-likelihood tier + fertility tier + US-MEC tier documented; treatment goal set
9. 9TREATMENT
   Ladder. Step 1: NSAID first-line — naproxen 500 mg PO then 250 mg q8h, ibuprofen 400–600 mg q6h, or mefenamic acid 500 mg then 250 mg q6h, start with/just before flow ×3–5 d (Cochrane Marjoribanks 2015 OR 4.37 [95% CI 3.76–5.09]; NSAID>paracetamol OR 1.89); + heat (≈ NSAID-equivalent) and regular exercise (Cochrane SMD −1.86). Step 2 hormonal (US-MEC-gated): combined oral contraceptive — CONTINUOUS regimen preferred over cyclic for endometriosis-suggestive disease (Cochrane Schroll 2023 SMD −0.58 vs placebo; continuous vs cyclic SMD −0.73); LNG-IUS; oral progestin (dienogest 2 mg/d — VAS −27.4 vs −15.1 mm placebo, Δ −12.3 mm P<0.0001, Strowitzki 2010 PMID 20444534), depot or implant progestin. Step 3: if 3–6-mo empiric trial fails → TVUS then MRI + gynae referral. Step 4 refractory endometriosis: GnRH antagonist — relugolix 40 mg + estradiol 1 mg + norethisterone acetate 0.5 mg once daily (built-in add-back; dysmenorrhoea responder Δ ~45–48% vs placebo, SPIRIT 1/2 PMID 35717987; lumbar BMD Δ only −0.70 to −0.78% with add-back) or elagolix 150 mg QD / 200 mg BID (dysmenorrhoea response 46–76% vs ~20% placebo, Elaris EM-I/II PMID 28525302) — add estrogen–progestin add-back + BMD surveillance if no built-in add-back; GnRH agonist leuprolide depot 3.75 mg IM monthly / 11.25 mg q3-monthly + add-back. Step 5: fertility-sparing pathway, chronic-pelvic-pain multimodal (central sensitisation), surgical/endometriosis-centre referral. (ESHRE 2022; ACOG CO 760; SOGC 437 2023)
   inputs: us_mec_comorbidity_inventory, nsaid_gi_renal_cv_risk
   actions: calc.us_mec
   advance: step appropriate to phenotype/US-MEC/fertility started; empiric-trial review point scheduled
10. 10DISPOSITION
    Outpatient for essentially all. Gynaecology / endometriosis-centre referral for refractory disease, DIE, fertility question, suspected Müllerian/outflow anomaly (adolescent — paediatric/adolescent gynae), or surgical candidacy (ESHRE 2022; ACOG CO 760)
    advance: outpatient plan + specialty referral (if indicated) secured
11. 11MONITORING
    Pain diary (NRS/VAS). MANDATORY 3–6-month empiric-trial review point: no clinical improvement → investigate secondary causes + adherence (the ACOG CO 760 T_test threshold; trial failure is itself a positive Bayesian update for endometriosis). Re-screen US-MEC at each hormonal change; GnRH step → add-back adequacy + BMD/DEXA surveillance + vasomotor/lipid review; hormonal-AE review (irregular bleeding RR 2.63, headache RR 1.51, nausea RR 1.64 — Cochrane Schroll 2023 PMID 37523477)
    inputs: empiric_trial_response_at_3_6_months, us_mec_comorbidity_inventory
    actions: calc.us_mec
    advance: trial response adjudicated at 3–6 mo; escalation or continuation decided; AE/BMD surveillance in place
12. 12FOLLOWUP
    Long-term hormonal suppression to menopause or until a fertility window (endometriosis is chronic + potentially progressive — ACOG CO 760); preconception/fertility-sparing planning; chronic-pelvic-pain biopsychosocial multimodal pathway for central-sensitisation overlap (Horne BMJ 2022 PMID 36375827; Mardon BJOG 2022 PMID 34919325); return precautions (new acute severe pain, fever, pregnancy, neurologic/vascular hormonal AE)
    advance: long-term suppression + fertility + chronic-pain plan + return precautions documented