title: Testosterone, thrombophilia, and thrombosis.
abstract: We describe thrombosis, deep venous thrombosis (DVT) pulmonary embolism (PE; n = 9) and hip-knee osteonecrosis (n = 5) that developed after testosterone therapy (median 11 months) in 14 previously healthy patients (13 men and 1 woman; 13 Caucasian and 1 African American), with no antecedent thrombosis and previously undiagnosed thrombophilia-hypofibrinolysis. Of the 14 patients, 3 were found to be factor V Leiden heterozygotes, 3 had high factor VIII, 3 had plasminogen activator inhibitor 1 4G4G homozygosity, 2 had high factor XI, 2 had high homocysteine, 1 had low antithrombin III, 1 had the lupus anticoagulant, 1 had high anticardiolipin antibody Immunoglobulin G, and 1 had no clotting abnormalities. In 4 men with thrombophilia, DVT-PE recurred when testosterone was continued despite therapeutic international normalized ratio on warfarin. In 60 men on testosterone, 20 (33%) had high estradiol (E2 >42.6 pg/mL). When exogenous testosterone is aromatized to E2, and E2-induced thrombophilia is superimposed on thrombophilia-hypofibrinolysis, thrombosis occurs. The DVT-PE and osteonecrosis after starting testosterone are associated with previously undiagnosed thrombophilia-hypofibrinolysis. Thrombophilia should be ruled out before administration of exogenous testosterone.
authors.affiliation: 1The Jewish Hospital Cholesterol Center, Cincinnati, OH, USA.
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Glueck
authors.forename: Caitlin
authors.initials: C
authors.lastname: Richardson-Royer
authors.forename: Reiker
authors.initials: R
authors.lastname: Schultz
authors.forename: Tim
authors.initials: T
authors.lastname: Burger
authors.forename: Fanta
authors.initials: F
authors.lastname: Labitue
authors.forename: Muhammad K
authors.initials: MK
authors.lastname: Riaz
authors.forename: Jagjit
authors.initials: J
authors.lastname: Padda
authors.forename: Dedrick
authors.initials: D
authors.lastname: Bowe
authors.forename: Naila
authors.initials: N
authors.lastname: Goldenberg
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D001779:Blood Coagulation Factors; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010020:Osteonecrosis / Q000097:blood / Q000139:chemically induced; D011655:Pulmonary Embolism / Q000097:blood / Q000139:chemically induced*; D013739:Testosterone / Q000009:adverse effects* / Q000097:blood / Q000627:therapeutic use*; D019851:Thrombophilia / Q000097:blood / Q000139:chemically induced*; D013927:Thrombosis / Q000097:blood / Q000139:chemically induced*
chemical_list: D001779:Blood Coagulation Factors; D013739:Testosterone
keywords: anticoagulants; blood coagulation factors; clinical thrombophilia; deep venous thrombosis; endocrinology; hypercoagulability; testosterone