Comparisons between orally administered pill and transdermal patch suggests that when estrogens are taken orally the risks of thrombophlebitis and pulmonary embolism are increased, an effect which is not seen with topical administration. Transdermal and transvaginal administration are not subject to first pass metabolism , and so lack the anabolic effects that oral therapy has on hepatic synthesis of Vitamin K dependent clotting factors .  This effect refers only to patches for post menopausal hormone replacement, which contain estradiol , not those used in oral contraceptive therapy, which contain ethinylestradiol . The latter is associated with an increased incidence of venous clot.  The WHI also showed an increased incidence arterial disease, namely stroke, in patients who began HRT after the age of 65, although this effect was not significantly present in those who began therapy during their fifth decade.