Endometrial responses to hormone replacement therapy: histological features compared with those of late luteal phase endometrium

We evaluated the histological features of the endometrium in relation to the bleeding pattern in a group of women receiving oral cyclical combined hormone replacement therapy (HRT), and compared the histological features with those of luteinizing hormone (LH)-dated endometrial biopsies obtained from healthy women at the time of sterilization. A total of 103 women completed 6 months of HRT therapy. All received a regimen of 2 mg oestradiol valerate daily, with 1 mg norethisterone added for the last 12 days of every 28-day cycle. Endometrial biopsies were scheduled for the end of the study (days 27-29 of the last cycle of therapy). Using the classical histological criteria, secretory endometrial changes were demonstrated in the majority (n = 89) of cases. The remaining were insufficient or inactive (n = 12), proliferative (n = 1) or atrophic (n = 1). Forty-nine women had a mean cycle length of less than 29 days (early bleeders), 50 women experienced cycles of more than 29 days (late bleeders) and four did not experience any bleeding. When the individual histological structures were examined, using image analysis, there were no statistically significant differences in the histological features when the long cycles in early bleeders were compared with those in late bleeders. LH-dated endometrium showed a high degree of homogeneity that was consistent with cycle day as described by the classic criteria, but HRT-treated endometrium exhibited a wide range of variability. HRT-treated endometrium from the subset of women who bled on or after day 29, and whose biopsies were obtained before the onset of bleeding, differed significantly from the endometrium taken at the corresponding phase of the physiological cycle. We conclude that the use of classical histological criteria, which are used in relation to the physiological cycle, in the study of HRT-treated endometria is inappropriate.