However,a recent research evidenced that the haplotype ER-1, does not have a strong effect on the estrogen-induced changes in haemostasis and inflammation risk markers for arterial and venous thrombosis. In fact, in this study no significant link between the different doses of ethinylestradiol and the effect was found ⁽⁵¹⁾.

In the Literature,  some cases of isolated or multiple artery occlusions in young women who smoke and who take oral contraceptives have been reported ^(47,52,53). Scarce data are available on involvement of progestins in the coagulation patho-mechanisms.

However, likely the vascular effects of progestins are mediated through progestin receptors as well as through down-regulation of estradiol receptors [54,55].

Estrogen and progestin receptors are localized in endothelial and smooth muscle cells of the vessel wall,  but there are differences in the response of vein and arteries to sex-steroids.

In the arteries, the progestin may inhibit the endothelium- dependent vasodilatator action of estrogens;  while,  in the veins progestin may increase the capacitance resulting in a decreased blood flow. 

Modification in hemostasis parameters seems to depend on the type and dose of progestogen, the presence of estrogen compound and the duration of use.  The risk of combined formulation could be a consequence of vascular action of progestins. 

In fact,  it seems that some progestins may up-regulate thrombin receptor expression, while other progestins did not ^(56,57).

Definitive conclusions about the significance of these findings have not yet been achieved.  In this light,  the prudent choice of hormonal regimen could be recommended. 

Using progestins with minimal vascular toxicity may lead to the safety of estrogen-progestin preparations for pre-menopausal women also with Hereditary Hemorrhagic Telangiectasia (HHT).  In fact,  COC use seems to be a promising alternative to usual treatment of nosebleeds, also as a first –line option in women HHT- affected.

In the meantime, this management avoids the risk of pregnancy ⁽⁵⁸⁾. Further studies are required to establish the role of progestins on haemostasis ⁽⁵⁹⁾.