Current status and future prospects of transdermal estrogen replacement therapy

The efficacy of transdermal E₂ in restoring serum E₂ levels to the premenopausal range and in affording relief of menopausal symptoms seems well-established. Importantly, Estraderm is providing a controlled sustained supply of E₂, the prevalent premenopausal estrogenic species. In doing so, Estraderm approximates normal physiology by serving, in effect, in the capacity of an artificial ovary. The minimal elevation of liver proteins seen in patients treated with Estraderm may aid in avoiding some of the complications traditionally seen with oral estrogen-replacement therapy. The medication appears to be well-tolerated, easy to use, and side effects are few. Comparative studies suggest that Estraderm 0.05 and 0.10 mg/d are approximately equivalent to Premarin 0.625 and 1.25 mg daily respectively, an observation supported by others. However, there is some evidence that the 0.05 mg/d patch is not as effective as 0.625 mg/d Premarin in relieving some vaginal complaints, and that a higher Estraderm dose (0.10 mg/d) may be necessary in some patients. The effect(s), if any, of transdermal E₂ administration on serum lipids, and the relevance of such changes to long-term cardiovascular morbidity, have not been well defined. In fact, the data on the actual effects of oral estrogen administration on cardiovascular morbidity seem less than clear-cut at this point in time. The vast majority of the literature pertaining to estrogen replacement therapy and cardiovascular disease in women does seem to imply that estrogen administration may, at the least, have no statistically significant impact on cardiovascular risk, and may in fact be cardioprotective. In a comprehensive review of the literature on this subject, Bush and Barrett-Connor make the statement that 'estrogens have powerful effects on certain biologic parameters, the alteration of which could influence cardiovascular disease risk,' and further conclude that if this protective effect is indeed real, it would make a very compelling reason for routine estrogen replacement therapy. Currently, however, the issue remains controversial, and no long-term studies involving cardiovascular morbidity and mortality in women using transdermal E₂ exist. As noted earlier, perhaps long-term administration of Estraderm would result in changes in HDL and LDL patterns similar to those seen with oral Premarin. Even if this were not the case, Estraderm administration may have beneficial effects on long-term cardiovascular endpoints, and these endpoints must be evaluated before reasonable decisions can be made regarding the appropriateness of this form of estrogen therapy. Similarly, the question as to the efficacy of Estraderm in the prevention of postmenopausal osteoporosis remains unanswered. Despite the decreases in several indirect markers of bone resorption seen with Estraderm administration, and the encouraging results of Ribot et al. showing increased bone mineral density after 1 year of Estraderm use, additional long-term studies are clearly essential if Estraderm is to become an acceptable form of estrogen-replacement therapy.