Different effects of oral and transdermal hormone replacement therapies onFactor IX, APC resistance, t-PA, PAI and C-reactive protein - A cross-sectional population survey

The effects of hormone replacement therapy (HRT) on thrombosis risk, thromb otic variables, and the inflammatory marker C-reactive protein (CRP) may va ry by route of administration (oral versus transdermal). We studied the rel ationships of 14 thrombotic variables (previously related to cardiovascular risk) and CRP to menopausal status and to use of HRT subtypes in a cross-s ectional study of 975 women aged 40-59 years. Our study confirmed previousl y-reported associations between thrombotic variables and menopausal status. Oral HRT use was associated with increased plasma levels of Factor IX, act ivated protein C (APC) resistance, and CRP; and with decreased levels of ti ssue plasminogen activator (t-PA) antigen and plasminogen activator inhibit or (PAI) activity. Factor VII levels were higher in women taking unopposed oral oestrogen HRT. The foregoing associations were not observed in users o f transdermal HRT; hence they may be consequences of the "first-pass" effec t of oral oestrogens on hepatic protein synthesis. We conclude that differe nt effects of oral and transdermal HRT on thrombotic and inflammatory varia bles may be relevant to their relative thrombotic risk; and suggest that th is hypothesis should be tested in prospective, randomised studies.