OESTROGEN METABOLISM PATHWAYS WHAT BLOOD TESTS MISS — AND WHAT THE DUTCH PLUS REVEALS OESTRADIOL (E2) Primary circulating oestrogen Blood test shows level only — not fate CYP1A2/1B1 2-hydroxylation CYP1B1 4-hydroxylation CYP3A4 16-hydroxylation 2-OH PATHWAY ✓ PROTECTIVE · PREFERRED 2-methoxyoestrone (inactive metabolite) Cleared efficiently via methylation Anti-proliferative properties Associated with reduced cancer risk Requires COMT enzyme + B vitamins DIM · Broccoli family vegetables ✓ Eliminated safely via liver → bile → stool 4-OH PATHWAY ⚠ GENOTOXIC POTENTIAL 4-catechol oestrogens (reactive quinones if not cleared) Can form DNA adducts Elevated if COMT variant (MTHFR) Requires glutathione for clearance NAC · Glutathione support · Methylation cofactors (B2, B6, B12, folate) ⚠ Cleared IF methylation sufficient — tested on OAT / DUTCH 16-OH PATHWAY ✗ PROLIFERATIVE · AVOID 16α-hydroxyoestrone (E3-like) (strongly oestrogenic metabolite) Strongly binds oestrogen receptors Drives breast tenderness, weight gain Elevated by obesity, gut dysbiosis I3C · Calcium-D-Glucarate · GI-MAP beta-glucuronidase reduction ✗ Recirculates if not cleared gut bacteria reactivate via ß-glucuronidase WHAT THE DUTCH PLUS MEASURES — AND WHAT IT CHANGES Woman A: Same blood oestrogen. Feels well. Metabolising via 2-OH → safe metabolites → efficient clearance 2:16 ratio: HIGH (protective) · DUTCH Plus confirms Intervention: maintain · continue methylation support Woman B: Same blood oestrogen. Symptomatic. Metabolising via 16-OH → proliferative → gut recirculating 2:16 ratio: LOW · DUTCH Plus + GI-MAP required Intervention: DIM · I3C · gut protocol · methylation support DETECTIVE HEALTH · STEPHEN DUNCAN MSC FDN-P · DUTCH PLUS HORMONE TESTING · DETECTIVE-HEALTH.COM