A PROSPECTIVE RANDOMIZED CONTROLLED-STUDY COMPARING THE MORPHOLOGICALAND BIOCHEMICAL RESPONSES OF THE ENDOMETRIUM TO 2 DIFFERENT FORMS OF PERIOD-FREE HORMONE REPLACEMENT THERAPY

Thirty postmenopausal women were randomized to receive either continuo us combined (cc) 2 mg oestradiol valerate and 0.7 mg norethisterone ac etate hormone replacement therapy (HRT) daily (15 women) or tibolone 2 .5 mg daily (15 women) and were monitored to determine the relationshi p between the two biochemical markers placental protein 14 (PP14) and the glycoprotein CA125, endometrial histology and occurrence of irregu lar bleeding after 12 months of treatment. The concentrations of PP14 and CA125 in plasma and uterine flushings before and after therapy wer e measured and their concentrations were associated with the histology of endometrial biopsies obtained on the same day as venesection and e ndometrial flushing. The levels of PP14 in uterine flushings were sign ificantly increased after the administration of both types of HRT (P < 0.05 for tibolone and P < 0.001 for ccHRT). However, the concentratio ns of PP14 found in flushings after ccHRT were considerably greater th an those found in flushings after tibolone; levels were increased abou t 150-fold by ccHRT and 6-fold by tibolone (P < 0.001). Plasma concent ration of PP14 after both types of HRT were also significantly raised to a similar degree (P < 0.01). In contrast, the concentration of plas ma and uterine CA125 were unchanged by either treatment, Histological analysis of the endometrium from women after 12 months of HRT treatmen t showed that 86% (6/7) of women on ccHRT had secretory activity as co mpared to 44% (4/9) women on tibolone (P < 0.05). Women with higher po st-HRT uterine PP14 concentration were more likely to have irregular b leeding (P < 0.05). Our studies have shown that endometrial PP14 but n ot CA125 concentrations are raised to a significant degree by two diff erent forms of period-free HRT regimens, Increased PP14 concentrations in uterine flushing may suggest endometrial stimulation of some form and predict the predilection to irregular bleeding. Thus uterine PP14 concentrations may be used to monitor endometrial responses in women o n HRT.