Haemostatic effects of supraphysiological levels of testosterone in normal men.
The effects of exogenous testosterone on the haemostatic system were studied in a group of 32 healthy men undergoing a clinical trial of hormonal male contraception. The men received 200 mg testosterone oenanthate (TE) weekly i.m., and plasma samples were taken pretreatment, at defined time points up to 52 weeks of treatment, and 4 and 8 weeks after discontinuing TE. This dose of TE caused a 2-fold increase in trough plasma testosterone levels. TE caused a fall in plasma fibrinogen concentration after 16 weeks of treatment. This was sustained for the duration of TE treatment and recovered to pretreatment levels during the recovery phase. There was also a sustained fall in the level of C4b binding protein which showed a rebound to levels above pretreatment during recovery. Levels of antithrombin III and prothrombin fragment F1.2 rose initially during TE treatment, and levels of protein C, protein S (free) and plasminogen activator inhibitor fell, but the concentrations of these factors all returned to pretreatment levels during continued treatment. There was no change in the plasma concentrations of beta-thromboglobulin, tissue plasminogen activator, protein S (total), or D-dimer. There was a sustained increase in haemoglobin concentration and haematocrit, without any change in platelet count. The observed changes were consistent with mild activation of the haemostatic system during initial treatment with testosterone. After several months the raised activation markers had returned to pretreatment levels indicating that a new equilibrium had been established which did not appear to be prothrombotic.(ABSTRACT TRUNCATED AT 250 WORDS)
Anderson
R A
RA
MRC Reproductive Biology Unit, Royal Infirmary, Edinburgh, Scotland, UK.
Ludlam
C A
CA
Wu
F C
FC
D000328:Adult; D000990:Antithrombin III / Q000032:analysis; D001798:Blood Proteins / Q000032:analysis*; D005340:Fibrinogen / Q000032:analysis; D006487:Hemostasis / Q000187:drug effects*; D006801:Humans; D008297:Male; D010446:Peptide Fragments / Q000032:analysis; D011516:Prothrombin / Q000032:analysis; D012307:Risk Factors; D013076:Sperm Count / Q000187:drug effects; D013092:Spermatogenesis-Blocking Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D013739:Testosterone / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D013927:Thrombosis / Q000139:chemically induced* / Q000453:epidemiology
D001798:Blood Proteins; D010446:Peptide Fragments; D013092:Spermatogenesis-Blocking Agents; C045879:prothrombin fragment 1.2; D013739:Testosterone; D000990:Antithrombin III; D011516:Prothrombin; D005340:Fibrinogen