Development and validation of an objective method of determining skin erythema to transdermal oestradiol patches

Abstract

IntroductionOne problem which has limited the acceptance of transdermal oestradiol patches is skin reaction at the site of patch application. The reported incidence ranges up to a maximum of approximately 40%14, with a smaller percentage of women discontinuing therapy. Skin reactions typically consist of erythema and oedema, with more severe reactions such as blistering occumng occasionally.The original patch (Estraderm TTS, Ciba-Geigy, Basel, Switzerland) consisted of a fluid filled reservoir containing oestradiol, covered by a semi-permeable inner membrane and kept in contact with the skin by a ring of adhesive. This was referred to as a 'reservoir' patch. Subsequently, the 'matrix' patch was developed. This looks quite different and contains oestradiol distributed in adhesive across the whole of the patch surface. Anecdotal and published reports"' suggest that the incidence of skin reactions differs between reservoir and matrix patch systems.Any study relying on subjective assessment of skin changes is potentially confounded by observer bias. This can never be excluded in a comparison of vkually dissimilar patches. Therefore we have developed an objective method of measuring patch site skin irritation using photographic digital image analysis. Methods Study designWe recruited 26 Caucasian women who had previously discontinued transdermal oestradiol therapy because of a skin reaction. Those with active dermatological disease or using non-inhaled corticosteroids were excluded. We enrolled them into a prospective randomised cross-over study of a reservoir and a matrix Correspondence: Dr D. Ross, Menopause Clinic, King's College Hospital, Denmark Hill, London SE5 9RS, UK.patch5. The patch systems compared were Estraderm TTS and Evorel (Janssen-Cilag Ltd, Saunderton, UK). Women used each patch, in randomly determined order, for eight weeks at the dose of 50 pg/24 h; the patches were changed twice weekly. Women with an intact uterus also received progestogen. This was usually in oral form, but if a transdermal progestogen was used, women were instructed to apply the progestogen-releasing patch on the opposite side of their body to that on which the study patch was applied. Full details of the clinical methodology are found elsewhere5.Women who experienced an unacceptable skin reaction could stop applying the current treatment at any time. Those stopping the first course of treatment progressed immediately to the second; those stopping the second treatment left the study. At each change of patch, women recorded the degree of local redness, swelling and itching on a diary card. Standardised clinical photography of patch sites was performed at the end of each phase. Photographic methodsThe site from which the most recent patch had been removed was photographed (Fig. 1). The timing of every visit for photography, including those following premature discontinuation, was standardised so that the last patch had been removed between 12 and 18 hours previously. Photographs of the patch site were taken using a 35 mm Nikon FM...