Are pharmacological considerations of relevance in hormone replacement therapy for prevention of chronic disease?

Up to now only two placebo-controlled intervention studies exist which evaluate the effect of hormone replacement therapy (HRT)on clinical endpoints using sufficient sample sizes. The negative outcomes of these studies such as increased cardiovascular and breast cancer risk led to extrapolations onto the complete therapeutic HRT field. This is unscientific considering pharmacological issues. In both studies only one HRT preparation was tested, conjugated equine oestrogens (CEE) combined with medroxyprogesterone acetate (MPA), using one fixed dosage combination. CEE is a variable mixture containing over 200 chemical substances, at least 10 oestrogen components and steroids with progestogen or androgen properties. Since all menopausal symptoms are caused by oestradiol deficiency it seems reasonable to replace the human oestrogen which is pharmacologically by no means comparable with the biological extract CEE. Concerning the combination with a progestogen negative cardiovascular effects are of importance and might be more predominant with MPA than with other progestogens. In addition low-dose HRT regimens should be tested, whereby transdermal application forms of both oestrogens and progestogens seem of special advantage.