Oral versus non-oral hormone replacement therapy: how important is the route of administration?

Although there are differences in the pharmacokinetic profiles of oral and non-oral routes of administration the clinical relevance of these differences remains to be determined. Likewise, there are differences in the metabolic and haemostatic effects of different routes of administration of oestrogen but these may have clinical relevance. For some parameters, such as lipids and lipoproteins, glucose and insulin metabolism, there are greater benefits from oral administration; for others, particularly haemostatic changes and effects on CRP, there are advantages from transdermal administration. For the potential benefits of HRT on CHD, these differences probably have less impact than the effect of the dose of hormones used and the lowest effective should be prescribed. Irrespective of dose, certain small sub-groups of patients should be specifically treated with an oral regimen eg those with lipid and lipoprotein abnormalities and impaired glucose tolerance whereas others should be treated with a transdermal regimen eg those with a personal or relevant family history of venous thrombosis. However, the vast majority of patients possess none of these risk factors and for them it will come down to personal preference. The availability of different combinations and doses of hormones, as well as different routes of administration, allows HRT to be tailored to the individual and there are few women for whom a suitable form of HRT cannot be found. Although data are lacking we believe it unwise to believe that fully transdermal combination therapy will not impact on risk of incident breast cancer. Based on current evidence transdermal HRT may also cause more irregular and breakthrough bleeding with sequential and continuous therapies than oral counterparts.