In contrast to progestogen-only birth control, the addition of progestins to oral estrogen therapy, including in combined birth control pills and menopausal hormone therapy, is associated with a higher risk of VTE than with oral estrogen therapy alone. The risk of VTE is increased by about 2-fold or less with such regimens in menopausal hormone therapy and by 2- to 4-fold with combined birth control pills containing ethinylestradiol, both relative to non-use. In contrast to oral estrogen therapy, parenteral estradiol, such as with transdermal estradiol, is not associated with a higher risk of VTE. This is likely due to its lack of first-pass effect in the liver. Research is mixed on whether addition of progestins to transdermal estradiol is associated with a greater risk of VTE, with some studies finding no increase in risk and others finding higher risk. Unlike the case of transdermal estradiol, VTE risk is not lower with ethinylestradiol-containing contraceptive vaginal rings and contraceptive patches compared to combined birth control pills with ethinylestradiol. This is thought to be due to the resistance of ethinylestradiol to hepatic metabolism.