Piperazine oestrone sulphate and interrupted norethisterone: effects on the postmenopausal endometrium

Objective To assess the effects on the postmenopausal endometrium of two do ses of oral piperazine oestrone sulphate and interrupted norethisterone in comparison with a continuously combined regimen and placebo. Design A prospective randomised trial. Participants Two hundred healthy postmenopausal women. Methods Random assignment to two years of treatment with alternating three- day cycles of 1.5 mg piperazine oestrone sulphate and 1.5 mg piperazine oes trone sulphate + 0.7 mg norethisterone (highEP), or alternating three-day c ycles of 0.75 mg piperazine oestrone sulphate and 0.75 mg piperazine oestro ne sulphate + 0.35 mg norethisterone (lowEP), or 2 mg 17 beta-oestradiol co ntinuously combined with 1 mg norethisterone acetate (E-2+NETA), or placebo . Main outcome measures Effect of treatment on endometrial histology, endomet rial thickness, occurrence of uterine bleeding, endometrial oestrogen and p rogesterone receptor content, endometrial isocitrate dehydrogenase activity , and serum placental protein 14. Results The incidence of bleeding declined with time. In the second treatme nt year, the women receiving lowEP reported on average 7.3 days of bleeding , highEP 16.7 days, and E-2+NETA 11.2 days. Histological assessment of endo metrial biopsies revealed an atrophic or slightly secretory endometrium. Se rum placental protein 14 increased slightly, but was statistically highly s ignificant, during treatment, but no cyclical variation was observed. Endom etrial isocitrate dehydrogenase was low in all three hormone groups and the same low level of endometrial oestrogen receptor and progesterone receptor was found comparable to the level in the placebo group. Conclusions Histological and biochemical assessment of the endometrium show ed that interrupted hormone replacement therapy induced the same pattern in endometrial parameters as continuous combined hormone replacement therapy.