Primary choice of estrogen and progestogen as components for HRT: a clinical pharmacological view

Prescribing hormone replacement therapy (HRT) requires consideration of the selection of its two components, the estrogen and the progestogen. In terms of the estrogen, the decision is mainly whether to use estradiol (E2) or conjugated equine estrogens (CEE). These are the components needed to efficiently treat climacteric symptoms or/and prevent osteoporosis, currently the only labeled indications. There is still controversy regarding the adequate dosages comparing E2 and CEE; however, the consensus is that the differences in the efficacy of E2 and CEE are not a real issue. Therefore, other criteria have to be used. The first reason to add the progestogen is to avoid the development of endometrial cancer (i.e. to achieve 'endometrial safety'). Any available 'fixed-combined' HRT preparation has to be tested for sufficient endometrial efficacy, because the first question the health authorities ask before product registration relates to endometrial safety. We can generally rely on the endometrial safety of these fixed-combined products. However, it could be that we want to use 'free' combinations, which are necessary if we use transdermal E2 (patches, gel, spray), but also to individualize schedules, for example when treating bleeding problems. The question here is how to attain knowledge about the endometrial efficacy of the different progestogens and how to monitor therapy. We will try to answer these two questions from a 'clinical pharmacology' point of view, as a discipline which preferably considers pharmacological properties, but also relating to clinical practice, to achieve individualized therapy with optimal efficacy, best tolerability and minimal risks.