The effects of oestrogen administration on the plasma free protein S and C4b-binding protein

Melissari, E.; Kakkar, V.V.

Thrombosis Research 49(5): 489-495


ISSN/ISBN: 0049-3848
PMID: 2967557
Accession: 006663140

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This study was undertaken to evaluate the effects of oestrogen administration (low dose as an oral contraceptive or higher dose as a hormone replacement therapy) on the levels of plasma free protein S and C4b-binding protein. The participants were 59 women aged 18-49 years, divided into 2 groups: A and B. Group A was composed of 22 post-menopausal women on a hormonal replacement therapy programme (HRT) consisting of 2mg daily oestradiol valarate for 21 days. Group B was divided into subgroup B1: 18 women who had been on oral contraceptive for at least one year and subgroup B2 (control): 17 women who were not pregnant and not taking any oral contraceptive. In this study were also included two young women who both suffered from severe thromboembolic disease a few months after initiation of oral contraceptive. The first was 25 years old, with congenital moderately decreased prekallikrein (activity and antigen 40% and 45% respectively) and the second was a 21 year-old woman with congenital moderately decreased plasminogen activity and antigen (45%). In both cases, family members with similarly reduced levels of prekallikrein (PK) and plasminogen (PLG) respectively were free from any thromboembolic disease and had normal protein S levels. In Group A, 22 women at the end of the first cycle of treatment, had lower levels of free protein S (p < 0.001) than before the initiation of HRT. In subgroup B1, the levels of free protein S were found to be significantly lower than in subgroup B2 (p < 0.001). Although the C4b-binding protein was 20% lower in subgroup B1 than in subgroup B2, this does not represent a significant difference. Since an association between oral contraceptive use and incidence of venous thromboembolism without predisposition to thrombosis has been consistently observed in case-control and cohort studies, we conclude that oestrogen reduces free protein S in both group A and subgroup B1-that is, the group receiving higher dosage as an HRT for a period of 21 days, and the subgroup B1 receiving low doses as an oral contraceptive over 12 months, whose mild deficiency in a factor may predispose them to thrombosis although hitherto silent.