Objective: To investigate the effects of a hormone replacement therapy regime of continuous oestrogen and interrupted progestogen, administered transdermally, on the endometrium of postmenopausal women, the pattern of bleeding and relief of menopausal symptoms.
Design: Volunteer pilot study of up to six months duration involving weekly application of an oestrogen-only skin patch releasing 50 microg oestradiol per day interspersed with a combined oestrogen and progestogen patch releasing 50 microg oestradiol and 250 microg norethisterone acetate per day for three days. Transvaginal ultrasound measurements of endometrial thickness and endometrial biopsies were performed in the third month of treatment at the end of both an oestrogen-only phase of treatment and a combined oestrogen-progestogen phase.
Setting: Specialist community menopause clinic, Dean Terrace Centre, Edinburgh.
Participants: Fifteen healthy postmenopausal women.
Main outcome measures: Effect of treatment on endometrial histology, the immunolocalisation of oestrogen and progesterone receptors and the cell proliferation marker Ki 67 after three months of treatment and the proportion of women without bleeding at six months.
Results: Treatment provided relief of hot flushes and by the sixth month of study 10 of the 14 women who completed treatment had no vaginal bleeding (71%). No endometrial hyperplasia or atypical changes were observed in biopsies and ultrasound measurements of endometrial thickness demonstrated a thin endometrium. Reduced immunostaining for Ki 67 was observed in endometrium from the combined phase of treatment compared with the oestrogen-only phase, consistent with a progestogenic-antagonism of proliferation. Exposure to progestogen did not suppress steroid receptors as similar immunostaining was observed in both treatment phases.
Conclusions: Continuous oestrogen and interrupted progestogen administered transdermally offers promise as a novel bleed-free hormone replacement therapy for postmenopausal women.