Hormonin

This study was conducted to assess endometrial protection in women on a cyclical combined hormone replacement regimen with 1 mg norethisterone BP, and to evaluate the use of the bleeding pattern and serum alpha 2-PEG in monitoring the endometrial response to exogenous hormone therapy. Fifty-one postmenopausal women attending the Menopause Research Unit at Leicester Royal Infirmary, UK, completed the study. All patients were at least 1 year after the menopause, with an average of 26 months since the last menstrual period. All women were prescribed a regimen of two tablets of Hormonin (oestriol 0.27 mg, oestrone 1.4 mg, and oestradiol 0.6 mg) continuously, with 1 mg of norethisterone added for 12 days out of each 28-day treatment cycle. Menstrual diaries were collected and analysed. The secretory changes were assessed by histology, menstrual bleeding pattern and a biological marker of secretory activity (alpha 2-PEG). Withdrawal bleeding occurred on average on days 11, 12, 11, 12 and 13 on months 2, 3, 6, 9 and 12, respectively. There was a poor degree of consistency in the bleeding pattern. The level of alpha 2-PEG increased from the average baseline measurement of 2.7 ng/ml (S.D., 4.12) to 8.5 ng/ml (S.D., 4.16) after progestogen treatment. This rise, although significant, did not correlate with the uterine bleeding pattern. There was no statistically significant correlation between the level of alpha 2-PEG and endometrial histology. The findings highlight the fact that cycle predictability on HRT, as exemplified in this regimen, is poor. The level of alpha 2-PEG is a poor predictor of the endometrial histology and has a poor correlation with the day of onset of bleeding.

The absorption, metabolism and clearance of oestradiol, oestrone and oestriol from the peripheral circulation were investigated in five postmenopausal women after the oral administration of Hormonin (oestradiol 600 μg, oestrone 1400 μg, oestriol 270 μg) daily for five consecutive days. In addition the concentrations of plasma oestrone‐3‐sulphate, oestrone‐3‐glucuronide, LH and FSH were determined in the same plasma samples. The maximum concentrations of each steroid in peripheral plasma and the time intervals during which the peak occurred after ingestion of the last tablet were:—oestrone (750 to 2116 pmol/1, 0·5 to 6·0 hours), oestradiol (246 to 813 pmol/1, 1 to 8 hours), oestriol (173 to 241 pmol/1, 5 to 12 hours), oestrone‐3‐glucuronide (32·2 to 78·8 nmol/1, 0·5 to 3·0 hours) and oestrone‐3‐sulphate (21·9 to 39·0 nmol/1, 1 to 7 hours). The mean factorial increases in the concentration of each compound during the first 12 hours post‐treatment over the baseline values were:—oestrone (4·1); oestradiol (4·4); oestriol (1·7); oestrone‐3‐sulphate (2·6) and oestrone‐3‐glucuronide (8·1). After treatment, the concentration of plasma oestradiol remained significantly higher than the baseline values (p <0·025) for 24 hours and the values for each subject were within the normal range for premenopausal women. Moreover, there was a significant reduction (p < 0·025) in the level of circulating LH. It is concluded that the simultaneous administration of oestrone, oestradiol and oestriol, by mouth, to postmenopausal women is a good approach to maintaining an appropriate concentration of oestradiol in peripheral plasma.