With transdermal estradiol substitution the so called "primary liver passage" is avoided. Taking into account also the low dose of estradiol the risk of hepatic side effects can be reduced. On the other hand, it was assumed that for the same reason desirable lipid effects regarding cardiovascular protection may also not be possible, in contrast to oral estrogen treatment. Treating 26 postmenopausal women with the estradiol patch releasing 0.05 mg daily and with 1 mg oral norethisterone acetate, added at least during 10 days in each cycle, a significant reduction was observed in total cholesterol as well as in LDL- and VLDL-cholesterol of about 15-20%. HDL-cholesterol first showed a decrease and thereafter it increased again to basic level. It is supposed that the reason for this may be different effects on subfractions of HDL-cholesterol. The triglycerides were lowered to about 20%. This result is thought to be important because oral estrogens have been associated with increases in triglycerides. By lowering LDL-cholesterol as well as triglycerides, both serum lipids, most important with respect to cardiovascular protection, are shown to be influenced positively.