Maturitas 38 Suppl. 1 (2001) S1–S5 Hormone replacement therapy for the postmenopausal woman Claus Christiansen * Center for Clinical and Basic Research, Ballerup Byej 222, 2750 Ballerup Denmark www.elsevier.com/locate/maturitas 1. Introduction Hormone replacement therapy (HRT) has many important benefits and overall seems to increase life expectancy. In spite of this, hot flushes are still the main reason for prescribing HRT, and the majority of women will stop taking the treatment after 2–5 years. An important rea- son why women stop HRT after a relative short period of time is the fear of the adverse events of HRT. This fear, and especially the fear of in- creased breast cancer risk, overshadows all poten- tial benefits, however great they may be. This attitude is very entrenched and will probably not change until it has been firmly proven that the compounds and/or the doses/administration forms used do not cause any increase in the risk of breast cancer. Another important reason why women stop HRT is poor bleeding control. Some women accept monthly bleeding as long as it is regular, small in amount, and lasts for only a short time. Other women cannot accept bleeding at all. Bleeding control is obtained by the right combination of estrogen and progestogen both in terms of type and dose. What, therefore, is the right combination? First of all, this varies greatly from one woman to another. Secondly, there are some basic requirements that must be fulfilled.  The combination should absolutely prevent any endometrial hyperplasia either by inducing regular bleeding or by keeping the en- dometrium atrophic throughout.  The combination should retard bone loss by normalizing bone turnover.  The combination may not cause any significant negative changes in the serum concentrations of serum lipids and lipoproteins. Ideally, it should change all these cardiovascular disease- related risk factors in a positive direction. Therefore, a great deal of effort has been in- vested in developing HRT regimens that meet these requirements. Since the adverse effects of HRT are dose related, one focus has been to minimize the dose of estrogen. This may effec- tively be achieved firstly, by avoiding the hepatic first-pass effect that transforms a large amount of the ingested hormone into inactive or less active metabolites. Furthermore, it may be achieved by individualizing the dose so that every woman only gets the dose required. The novel intranasal ad- ministration form of 17-estradiol has been proven to fulfill these requirements [1,2]. This publication highlights the data that have recently been obtained in preclinical and clinical research with this new compound. * Tel.: +45-44-684600; fax: +45-44-684220. E-mail address: ccbr – ballerup@ccbr.dk (C. Christiansen). 0378-5122/01/$ - see front matter © 2001 Elsevier Science Ireland Ltd. All rights reserved. PII: S0378-5122(01)00198-0