Continuous transdermal oestrogen and interrupted progestogen as a novel bleed-free regimen of hormone replacement therapy for postmenopausal women

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 mu g oestradiol per day interspersed with a combined oestrogen and progestogen patch releasing 50 mu g oestradiol and 250 mu g 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 Ki67 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 IO of the 14 women who completed treatment had no vaginal bleeding (71%). No endometrial hyperplasia ol atypical changes were observed in biopsies and ultrasound measurements of endometrial thickness demonstrated a thin endometrium. Reduced immunostaining for Ki67 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.