{"id":"08393e48-469f-5478-9ecb-9ef7be01e4ea","stable_key":"182336c6-ed36-5ec6-8a09-25c31096262e:dim-estrogen-ratio","predicate":"increases","statement":"BR-DIM increased the urinary 2/16-alpha-hydroxyestrone ratio relative to placebo.","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"c1c85b5b-882a-5da1-9d8b-812ca151dfa9","mechanism_event_label":"A ratio changed; calling one estrogen universally good and another bad would go beyond the trial.","subject":{"id":"6009bdd4-f1b5-5867-b5c3-cdf7c9645cd0","slug":"dim","display_name":"3,3'-Diindolylmethane / DIM","entity_type_key":"small_molecule"},"object":{"id":"3973614c-dc93-5138-b444-175dd134b878","slug":"urinary-2-to-16-hydroxyestrone-ratio","display_name":"Urinary 2-hydroxyestrone to 16-alpha-hydroxyestrone ratio","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"c1c85b5b-882a-5da1-9d8b-812ca151dfa9","stable_key":"182336c6-ed36-5ec6-8a09-25c31096262e:dim-estrogen-ratio-event","event_type":"observed_intervention","label":"A ratio changed; calling one estrogen universally good and another bad would go beyond the trial.","description":"BR-DIM increased the urinary 2/16-alpha-hydroxyestrone ratio relative to placebo.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"33177d0a-6824-516a-b6dc-026c4d7b551e","slug":"2-hydroxyestrone","display_name":"2-Hydroxyestrone","entity_type_key":"small_molecule"},"role":"numerator","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"3dda3ddd-c4b5-55e2-8174-1b1dd8e55683","slug":"16-alpha-hydroxyestrone","display_name":"16-alpha-Hydroxyestrone","entity_type_key":"small_molecule"},"role":"denominator","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"6009bdd4-f1b5-5867-b5c3-cdf7c9645cd0","slug":"dim","display_name":"3,3'-Diindolylmethane / DIM","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"3973614c-dc93-5138-b444-175dd134b878","slug":"urinary-2-to-16-hydroxyestrone-ratio","display_name":"Urinary 2-hydroxyestrone to 16-alpha-hydroxyestrone ratio","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/dim-research/28560655.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"f4d3745a4c2211551e755b314eced209ac88e072b9e02cd97cbaa5eed8303f28\", \"start_char\": 0, \"end_char\": 1823, \"text_sha256\": \"f4d3745a4c2211551e755b314eced209ac88e072b9e02cd97cbaa5eed8303f28\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Randomized double-blind placebo-controlled trial","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"BR-DIM 150 mg twice daily for 12 months","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Biomarker and pharmacokinetic endpoints, not recurrence or survival. The causal enzyme mechanism and effect on tamoxifen clinical benefit were not determined.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"dim","display_name":"3,3'-Diindolylmethane / DIM","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"130 women prescribed tamoxifen; 98 completed","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"A ratio changed; calling one estrogen universally good and another bad would go beyond the trial.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[dim-p28560655] A randomized, placebo-controlled trial of diindolylmethane for breast cancer biomarker modulation in patients taking tamoxifen. (2017). https://pubmed.ncbi.nlm.nih.gov/28560655/ DOI: 10.1007/s10549-017-4292-7","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Estrogen biomarkers and tamoxifen metabolites","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"3111e8da-cba4-5268-864b-8166f5b27b5b","evidence_kind":"source_excerpt","locator":"Lines 1091-1102","start_line":1091,"end_line":1102,"excerpt":"### dim-estrogen-ratio\nBR-DIM increased the urinary 2/16-alpha-hydroxyestrone ratio relative to placebo.\nCondition category: normal\nnutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: A ratio changed; calling one estrogen universally good and another bad would go beyond the trial.\norganism: 130 women prescribed tamoxifen; 98 completed\ntissue_or_cell_type: Estrogen biomarkers and tamoxifen metabolites\nexperimental_model: Randomized double-blind placebo-controlled trial\nlimitations: Biomarker and pharmacokinetic endpoints, not recurrence or survival. The causal enzyme mechanism and effect on tamoxifen clinical benefit were not determined.\nexposure: BR-DIM 150 mg twice daily for 12 months\nevidence_span: {\"source_cache\": \"artifacts/dim-research/28560655.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"f4d3745a4c2211551e755b314eced209ac88e072b9e02cd97cbaa5eed8303f28\", \"start_char\": 0, \"end_char\": 1823, \"text_sha256\": \"f4d3745a4c2211551e755b314eced209ac88e072b9e02cd97cbaa5eed8303f28\"}\n[dim-p28560655] A randomized, placebo-controlled trial of diindolylmethane for breast cancer biomarker modulation in patients taking tamoxifen. (2017). https://pubmed.ncbi.nlm.nih.gov/28560655/ DOI: 10.1007/s10549-017-4292-7","model_system":"Randomized double-blind placebo-controlled trial","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. 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