Endometrial responses in artificial cycles: A prospective study comparing four different oestrogen dosages

Objective: To examine the endometrial response to four different regimens of oestrogen. Design: A prospective, randomized cross-over study. Setting: Jessop Hospital for Women, Sheffield. Subjects: Twenty one women with premature ovarian failure divided into three equal groups. Interventions: Four different regimens of hormone replacement therapy: variable, fixed 1 mg, fixed 2 mg and fixed 4 mg oestrogen dosages. Each woman received the variable dosage regimen in one cycle and crossed over to receive one of the three fixed dose regimens (1 mg, Group 1; 2 mg, Group 2; 4 mg Group 3) in another cycle. Main outcome measure: Ultrasonographic measurement of endometrial thickness and outpatient endometrial biopsy on day 19 of the artificial cycle; analysis of endometrial specimens by three separate methods: traditional histological criteria, morphometry and immunohistochemistry. Results: The endometrial response was similar in those treated with the variable and the fixed 2 mg or 4 mg dosage regimens. The response was suboptimal in those treated with the fixed 1 mg dosage regimen. Conclusions: Normal endometrial development requires adequate priming of the endometrium by oestrogen, which may be administered in a sequential, variable dosage fashion, or simply by a fixed daily dosage regimen. However, the minimum daily dose required is likely to be 2 mg of oestradiol valerate. No adverse effect on the endometrium was observed at a daily dose of 4 mg oestradiol valerate, which produced plasma levels of oestradiol above the reference ranges of the natural cycle.