HORMONE REPLACEMENT THERAPY BY THE TRANSDERMAL ADMINISTRATION OF ESTRADIOL AND NORETHISTERONE

The objective was to assess the efficacy and acceptability of a new transdermal norethisterone device as part of a hormone replacement therapy (HRT) regimen. The design was an open prospective clinical assessment for 6 months. The setting was the Academic Unit of Obstetrics and Gynaecology, Royal London Hospital, Whitechapel, London. Eighteen patients of confirmed menopausal status were recruited. Therapy consisted of continuous application of Estraderm TTS 50 (Ciba Laboratories) for a 28-day period, with the additional application of two norethisterone acetate patches in the last 12 days of this period. This schedule was repeated for six cycles. The main outcome measures were symptom and menstrual data - haematological indices, hepatic and renal function; lipid parameters; endometrial biopsy. The results showed a significant improvement in the patients' symptoms of hot flushes and sweating (P = 0.03). Of the 15 women who completed at least 6 months of medication, withdrawal vaginal bleeding was established at regular intervals in 9. One patient had a local irritant reaction to the patch. There were no significant changes observed in haematological indices, hepatic and renal function. There was a slight but not statistically significant decrease in the HDL cholesterol fraction when the patient was in the norethisterone phase of the cycle, but no change was observed between the beginning and end of the study. Histological examination of the endometrial biopsies showed features of secretory activity in 56% of samples after 6 months. There was no evidence of hyperplasia, pre-malignant or malignant changes in the remaining biopsies. The conclusion was that combined transdermal administration of oestradiol and cyclical norethisterone is likely to be an effective mode of administration of HRT. No adverse biochemical or haematological changes were demonstrated, the clinical significance of the decrease in HDL cholesterol fraction is uncertain. Histological changes demonstrated were compatible with the menstrual data obtained.