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Hormones, thrombophilia, and VTE

Systematic review
Results
Comment

The use of oral contraceptives and hormone replacement therapy is associated with increased risk of venous thromboembolism (deep vein thrombosis or pulmonary embolism). Thrombophilia is the propensity to develop thrombosis (blood clots) due to an abnormality in the system of coagulation. One might expect, therefore, that there would be an even higher risk of venous thromboembolism in women who both had a thrombophilia and who took oral contraceptives or hormone replacement therapy. A systematic review [1] confirms that.

Systematic review

The review performed some heroic searching to find prospective or retrospective studies in which the study population included women using oral contraceptives or hormone replacement therapy. Clinical outcomes that included incidence of venous thromboembolism or mortality had to be reported, with information on the presence or absence of any thromboembolic defect.

Results

For oral contraceptive use, seven studies were found, predominantly case-control studies comparing women with a venous thromboembolism event (VTE) with control women. The rate of oral contraceptive use in women with VTE events (61%) was about double that with controls (29%; Table 1).



Table 1: Results for association of venous thromboembolism with oral contraceptive or hormone replacement use, Factor V Leiden, or both



Number of
Percent with factor in women who
Factor
Studies
Patients
Had
VTE events
Had no
VTE events
Relative risk
(95%CI)
Oral contraceptive use
7
2530
61
29
2.0 (1.8 to 2.2)
Factor V Leiden, no OC
6
1617
19
6
3.5 (2.5 to 4.9)
Oral contraceptive and Factor V Leiden
6
1612
27
2
12 (7.9 to 19)
Hormone replacement therapy
2
359
62
38
1.7 (1.4 to 2.1)
Factor V Leiden, no HRT
2
221
21
7
3.1 (1.4 to 6.7)
HRT and Factor V Leiden
2
218
27
3
9.2 (3.5 to 24)


In women not taking oral contraceptives, the incidence of known thrombophilias was higher in those with a VTE. For factor V Leiden, where there were most data, the relative risk was 3.5 (95% CI 2.5 to 4.9). In women who had a VTE, use of oral contraceptive in the presence of Factor V Leiden occurred about 12 times more frequently than in control women who had not experienced a VTE (Figure 1). The relative risk was 12 (7.9 to 19). Although information for other thrombophilias was limited to information from only one or two trials, much higher risks were also seen for Prothrombin G20210A, antithrombin, protein C, and protein S deficiencies, and high levels of FVIIIc.



Figure 1: Use of OC with Factor V Leiden in women with and without VTE





There was only limited information for use of hormone replacement therapy and thrombophilia, but the results from two case-control studies was consistent with that from oral contraceptive use (Table 1).

Comment

The combination of oral hormone therapy together with an abnormality of coagulation is a bad thing. For oral contraceptives and factor V Leiden, the sum of the individual risks (5.5) was lower than the risk of the combined factors (12), and lower even than the lower confidence interval (7.9; Table 1). It may well be that the effect is supra additive.

Clearly oral contraceptives and hormone replacement therapy should be avoided in women with known defects in coagulation, but few women know whether they have or do not have these defects. Screening before use does not seem sensible, given the many different thrombophilias, and their low absolute incidence.

However, given the high incidence of thrombophilias in women who have had a thromboembolic episode (about 1 in 5 for Factor V Leiden alone), avoiding hormone therapy in these women would seem sensible.

Reference:

  1. 1 A Wu et al. Oral contraceptives, hormone replacement therapy, thrombophilias and risk of venous thromboembolism: a systematic review. Thrombosis and Haemostasis 2005 94: 17-25.

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