Transdermal systems: pros and tons

The estrogen concentrations obtained with transdermal therapeutic systems ( TTS) are closer to the premenopausal methods than those yielded by any othe r method currently available. Constant estradiol concentrations are achieve d, comparable with those seen earlier in the follicular phase. When hormone replacement therapy is given by mouth,the dosage of estradiol needed to re ach effective active ingredient levels is 40 times that used for TTS treatm ent, and then the levels fluctuate markedly with supraphysiological peaks a nd subnormal nadirs. The high doses are needed for oral administration beca use estrogen is very strongly metabolized during passage through the liver. The liver is "flooded," especially with oestrone, estriol, 16 alpha-hydroxy estrone and the catechol estrogens. Increased synthesis of hepatic proteins such as angiotensinogen or thyroxine-binding globulin (TBG) and various co agulation factors arises, and hyperlipoproteinemia can occur. With transder mal estrogen replacement,the oestradiol passes directly into the systemic c irculation and thus to the target organs. In the presence of liver disease, gastrointestinal disease, venous thromboembolism,and thyroid disease, tran sdermal estrogen replacement therapy is therefore indicated in preference t o the corresponding oral therapy. If the indications are strictly observed, estrogen treatment by the transdermal route can be justified even after ca rdiac infarction.