A prospective randomized controlled study comparing the morphological and biochemical responses of the endometrium to two different forms of 'period-free' hormone replacement therapy.
Thirty postmenopausal women were randomized to receive either continuous combined (cc) 2 mg oestradiol valerate and 0.7 mg norethisterone acetate hormone replacement therapy (HRT) daily (15 women) or tibolone 2.5 mg daily (15 women) and were monitored to determine the relationship between the two biochemical markers placental protein 14 (PP14) and the glycoprotein CA125, endometrial histology and occurrence of irregular bleeding after 12 months of treatment. The concentrations of PP14 and CA125 in plasma and uterine flushings before and after therapy were measured and their concentrations were associated with the histology of endometrial biopsies obtained on the same day as venesection and endometrial flushing. The levels of PP14 in uterine flushings were significantly increased after the administration of both types of HRT (P < 0.05 for tibolone and P < 0.001 for ccHRT). However, the concentrations of PP14 found in flushings after ccHRT were considerably greater than those found in flushings after tibolone; levels were increased about 150-fold by ccHRT and 6-fold by tibolone (P < 0.001). Plasma concentration of PP14 after both types of HRT were also significantly raised to a similar degree (P < 0.01). In contrast, the concentration of plasma and uterine CA125 were unchanged by either treatment. Histological analysis of the endometrium from women after 12 months of HRT treatment showed that 86% (6/7) of women on ccHRT had secretory activity as compared to 44% (4/9) women on tibolone (P < 0.05). Women with higher post-HRT uterine PP14 concentration were more likely to have irregular bleeding (P < 0.05). Our studies have shown that endometrial PP14 but not CA125 concentrations are raised to a significant degree by two different 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 on HRT.
Biomedical Research Unit, Jessop Hospital for Women, Sheffield, UK.
M A
MA
Okon
S
S
Lee
S M
SM
Laird
T C
TC
Li
D018394:CA-125 Antigen / Q000097:blood / Q000378:metabolism; D004717:Endometrium / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives; D015914:Estrogen Replacement Therapy / Q000379:methods*; D005260:Female; D000071816:Glycodelin; D006023:Glycoproteins / Q000097:blood / Q000378:metabolism; D006801:Humans; D008598:Menstruation / Q000187:drug effects; D008875:Middle Aged; D009640:Norethindrone / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077563:Norethindrone Acetate; D009652:Norpregnenes / Q000008:administration & dosage; D011257:Pregnancy Proteins / Q000097:blood / Q000378:metabolism; D011446:Prospective Studies
D018394:CA-125 Antigen; D000071816:Glycodelin; D006023:Glycoproteins; D009652:Norpregnenes; C045246:PAEP protein, human; D011257:Pregnancy Proteins; D004958:Estradiol; D000077563:Norethindrone Acetate; C027385:tibolone; D009640:Norethindrone