Long-term hormone replacement treatment in menopause: new choices, old apprehensions, recent findings

In recent years there has been an increase in the use of parenteral oestradiol as an alternative to the conventional oral preparations used in hormone replacement treatment (HRT) in menopause, such as conjugated equine oestrogens (CEE). The latter have been subject in the past to apprehensions, partly due to misunderstanding and oversimplification but also in relation to problems that have arisen during the history of HRT, for example the increase in endometrial cancer risk deriving from the use of non-progestogen-opposed treatment. However, confidence in long-term HRT comes from the epidemiological findings, which refer mainly to the use of oral CEE unopposed by progestogen: a reduced risk of osteoporotic fractures and of cardiovascular disease, and a very limited risk of breast cancer. Oral oestrogens produce marked hepatocellular effects. These effects are, on the whole, favourable from the point of view of cardiovascular risk. In addition, it cannot be excluded that some hepatocellular effects of oral oestrogen, for example increased sex hormone binding globulin levels and reduced circulating insulin-like growth factor I activity, offer protection to the breast. As progestogen supplementation is needed in non-hysterectomized women, priority should be given to preparations, such as progesterone or dydrogesterone, that feature good endometrial activity without opposing oestrogen hepatocellular effects.