There are several preparations available for hormone substitution in the postmenopause. The aim of this paper is to give a short review on oral and transdermal hormone substitution therapy. Are there different effects, side effects or metabolic interactions? Both the oral and the transdermal application are similar in reduction of menopausal symptoms. Neither vaginal cytologic differences, nor different bleeding patterns and no increase in weight or blood pressure changes can be observed with either application form. Despite a local irritation of the skin (3-7%) with transdermal oestradiol, only 4% of the patients show systemic side effects either with oral or transdermal hormone substitution. The oral administration results in higher 17 beta-oestradiol levels, higher oestrone levels and an increase in some liver proteins, possibly as a result of the first pass effect of the liver. The cardioprotective effects of oral hormone substitution are well known. Furthermore transdermal oestradiol therapy results, also in a decrease of cholesterol and atherogenic LDL-C levels. In contrast to oral oestrogens, no effect on triglycerides or its decrease can be observed; in view of conflicting results regarding HDL-C, further studies are necessary. With both applications, there are no clinically relevant alterations in thyroid, carbohydrate- or blood coagulation metabolism: Even the prevention of osteoporosis in postmenopausal women, which is establish with oral hormone therapy, can also be observed with transdermal hormone substitution.