The effects of postmenopausal hormone replacement therapy on hemostatic variables: a meta-analysis of 46 studies

Abstract

The aim of the study was to summarize and reanalyze all available data from the literature to study the overall effect of postmenopausal hormone replacement therapy (HRT) and its various forms on hemostatic variables. Studies were identified from literature searches by Medline and Index Medicus, review articles and personal communications. Reference lists of all articles were checked to find additional studies. Principal investigators were contacted and asked to provide additional data if required. Data were collected separately for each factor of the hemostatic system. Studies written in any language were included. Each collection of studies was analyzed using standard methods for meta-analysis. A total of 76 arms of 48 studies were eligible for analysis. This included 6,119 women using HRT and 24,974 non-users. The age of investigated women was 40-68 years. HRT was associated with significantly decreased levels of fibrinogen, factor VIII, antithrombin III, and proteins C and S, but significantly increased plasminogen levels. HRT with estrogen alone or in combination with progestins, oral vs. transdermal regimens, different estrogen preparations and various progestins induced significantly different changes in many cases. In conclusion, HRT was associated with changes that could explain the increased rate of venous thrombotic events, and also with some changes that could account for beneficial vascular effects. Surprisingly, the addition of progestins induced favorable changes in many cases. Also, transdermal use was associated with more beneficial effects than oral regimens in some cases.

The action of ovarian hormones in cardiovascular disease

“…Factor IX has been shown to be increased in women taking HRT (Lowe et al, 2001). HRT preparations have also been associated with a decrease in plasma levels of Factor VIII (Acs et al, 2002). The combination of Factor IXa and Factor VIII promote the activation of Factor X.…”

“…This complex can also down-regulate the circulating levels of thrombin (dashed line with negative sign in Figure 2). In contrast to the above mentioned hormonal regulation of the coagulation cascades, combined estrogen and progestin treatments display anticoagulant activity by lowering the circulating levels of the fibrin precursor fibrinogen (Acs et al, 2002;Cushman et al, 1999;van Baal et al, 1999b;Norris et al, 2002; Table I). HRT has also been reported to increase fibrin turnover (Sidelmann et al, 2003).…”

Effects of either Tibolone or Continuous Combined Transdermal Estradiol with Medroxyprogesterone Acetate on Coagulatory Factors and Lipoprotein(a) in Menopause

“…Oral estrogens induce an increase in hepatic zymogens (factors VII, X, IX and II), while transdermal estrogen has a negligible influence [43] . Progestins, which must be added to estrogens, do not seem to be procoagulative, but actually seem to positively influence the fibrinolytic system, as measured, for example, by plasminogen activity [43][44][45] . Androgens may increase fibrinolytic capacity and reduce platelet aggregation [45][46][47] .…”