Bleeding Pattern, Endometrial Histology and Efficacy of Transdermal Estradiol and Sequential Estradiol/Norethisterone Acetate

Abstract

The aim of this study was to assess the effect of transdermal administration of estradiol (Estraderm TTS 100) followed by transdermal estradiol and norethisterone acetate (Estragest TTS) on gestagenic transformation of the endometrium, control of bleeding and postmenopausal symptoms in patients previously treated with Estraderm TTS 100 or an equivalent dose of estrogen. 20 postmenopausal patients entered this open, noncomparative, single centre study. Trial treatment consisted of Estraderm TTS 100, delivering O.1mg estradiol per day, followed by Estragest TTS, delivering 0.25mg norethisterone acetate and 0.05mg estradiol per day, both for 14 days over 18 cycles. Bleeding pattern, endometrial histology, psychological/menopausal symptoms (modified Women’s Health Questionnaire) and tolerability were studied. Bleeding was regular in 75% of the 285 cycles. The day of onset was on average day 11 and the duration was 7 to 8 days. A secretory endometrium was observed in 32 of 44 biopsies (performed during the combined phase) after 6 cycles and during the following year. Six biopsies (5 patients) showed a proliferative endometrium. Not a single case of hyperplasia was detected. No increase in menopausal symptoms and only a very slight increase in gestagen-related symptoms were observed during the second phase of the cycle.