Endometrial changes after long-term use of continuous oestrogen and cyclic progestogen.
Eight women with primary failure of ovarian function and twelve women undergoing the climacteric were treated sequentially with oestradiol-oestriol and norethisterone acetate (Trisequens and Trisequens Forte, Novo). After a mean treatment period of 5 yr (range 3-8 yr) endometrial biopsies were taken on day 11 or 12 at the end of an oestrogen-only phase. All biopsies showed the presence of a proliferative endometrium without any signs of hyperplasia or carcinoma in situ. Although cyclic oestrogen therapy can cause hyperplasia, a small dose of a progestogen (norethisterone acetate 1 mg) for 10 days in a 28-day cycle can prevent hyperplasia of the endometrium during long-term treatment.