Current hormone replacement therapy: what are the shortcomings? Advances in delivery

The introduction of transdermal and other parenteral delivery systems has broadened the range of options for hormone replacement therapy (HRT). Oral oestrogen is the most common initial therapy; however, direct absorption of oestradiol via the skin results in an oestradiol-oestrone ratio similar to that found in the pre-menopausal state. Both oral and transdermal oestrogen therapy have been shown to be equally effective in relieving climacteric symptoms, and in preventing osteoporosis or modifying some cardiovascular disease risk factors, although transdermal therapy tends to have fewer unwanted effects than oral. Satisfactory circulating oestradiol levels are achieved with skin patches, transdermal gel, or crystalloid oestradiol implants, and adding progestogen to protect the endometrium is well established. Sequential therapy with HRT usually produces a regular bleed, which is a major cause of patient dissatisfaction. The ideal HRT regimen is probably unobtainable, but the development of SERMs and other regimens that avoid bleeding will encourage long-term use.