HORMONE REPLACEMENT THERAPY BY THE TRANSDERMAL ADMINISTRATION OF ESTRADIOL AND NORETHISTERONE

The objective was to assess the efficacy and acceptability of a new tr ansdermal norethisterone device as part of a hormone replacement thera py (HRT) regimen. The design was an open prospective clinical assessme nt for 6 months. The setting was the Academic Unit of Obstetrics and G ynaecology, Royal London Hospital, Whitechapel, London. Eighteen patie nts of confirmed menopausal status were recruited. Therapy consisted o f 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 me nstrual data - haematological indices, hepatic and renal function; lip id parameters; endometrial biopsy. The results showed a significant im provement in the patients' symptoms of hot flushes and sweating (P = 0 .03). Of the 15 women who completed at least 6 months of medication, w ithdrawal 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 re nal function. There was a slight but not statistically significant dec rease in the HDL cholesterol fraction when the patient was in the nore thisterone phase of the cycle, but no change was observed between the beginning and end of the study. Histological examination of the endome trial biopsies showed features of secretory activity in 56% of samples after 6 months. There was no evidence of hyperplasia, pre-malignant o r malignant changes in the remaining biopsies. The conclusion was that combined transdermal administration of oestradiol and cyclical noreth isterone is likely to be an effective mode of administration of HRT. N o 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.