Haemostatic activation in post-menopausal women taking low-dose hormone therapy: Less effect with transdermal administration?

Abstract

Hormone therapy (HT) increases the risk of cardiovascular and thromboembolic disease in post-menopausal women. Recent studies have suggested that prothrombotic mechanisms are likely to be involved. Transdermal HT avoids the first-pass effect of oestrogen in the liver and may have a less marked effect on the haemostatic system than equivalent oral preparations. The majority of studies have compared HT preparations that have different formulations as well as routes of administration. We investigated changes in the haemostatic system in post-menopausal women using two pharmacologically similar HT preparations, which differed only in their route of administration. Three hundred forty-four healthy post-menopausal women were randomised to six months treatment with either a transdermal matrix patch containing 25 microg 17beta-estradiol/125 microg norethisterone acetate (NETA) applied every 3-4 days, or an equivalent oral preparation (estradiol 1 mg and NETA 0.5 mg given once daily). Oral treatment significantly reduced fibrinogen (p < 0.003), factor VIIc (FVIIc) (p < 0.00001), and antithrombin (AT) levels (p < 0.005); the effects in the transdermal group were less marked with no reduction in fibrinogen levels and lesser effect on FVIIc (p < 0.03) compared with oral treatment. Treatment type significantly affected fibrinolysis with lower plasmin-anti-plasmin (PAP) levels in the transdermal group (p < 0.003) and lower plasminogen activator inhibitor-1 antigen (PAI-1) (p < 0.012) and tissue plasminogen activator (tPA) antigen levels in the oral group (p < 0.002). Prothrombin fragment 1.2 and activated protein C (APC) resistance were not affected by either treatment. Transdermal HT has a less marked effect on coagulation than an equivalent oral preparation. Randomised trials are required to investigate whether this translates into less risk of cardiovascular and thromboembolic disease.

Hormone Replacement Therapy: Would it be Possible to Replicate a Functional Ovary?

“…The prothrombotic effects of oestrogen include a decrease in the levels of serum fibrinogen, factor VII, and antithrombin III. These effects are less pronounced in case of transdermal oestrogen but the evidence that transdermal oestrogen is safer for secondary prevention of CHD is lacking [ 27 , 28 ]. In addition, the choice and regimen of progesterone is important as there is some evidence that some progesterone like medroxy progesterone acetate (MPA) (used in WHI and HERS) might attenuate the cardiac benefit caused by oestrogen while norethindrone acetate or natural progesterone are not found to lessen the benefit of oestrogen.…”

Hormone therapy dose, formulation, route of delivery, and risk of cardiovascular events in women

“…Further, transdermal HT delivery avoids the “first pass” liver metabolism which increases serum coagulation factors, triglycerides, C-reactive protein, and a host of other factors; it also provides a more physiologic ratio of estradiol to estrone. 6-9 The health effects of the addition of progestogens, used in combination HT for women with an intact uterus, have only recently been compared to estrogen-alone with respect to coronary heart disease (CHD), stroke, and other health outcomes. For example, CVD outcomes from the WHI estrogen-alone trial showed no increased risk of myocardial infarction 10 whereas the WHI-CT of estrogen plus progestin demonstrated an overall increase in risk of CVD.…”

A case control study on the structural equation model of the mechanism of coagulation and fibrinolysis imbalance in chronic schistosomiasis

“…The main reason for this condition was related to the pathological basis of chronic schistosomiasis. A large number of eggs were deposited in the mesenteric vessels after schistosome infection [ 19 ] ; the eggs and antigens stimulated the vascular wall and activated the coagulation system. However, with the progression of disease stages, patients with chronic schistosomiasis developed a hypercoagulable state induced by the lack of anticoagulation activity, especially in advanced schistosomiasis patients with liver damage, which indicated worsening liver function associated with the development of disease.…”