ENDOMETRIAL MICROVASCULAR DENSITY DURING THE NORMAL MENSTRUAL-CYCLE AND FOLLOWING EXPOSURE TO LONG-TERM LEVONORGESTREL

The mechanisms that underlie progestogen-induced endometrial breakthro ugh bleeding are poorly understood. The aim of the present study was t o quantify endometrial microvascular density in 54 controls and 42 wom en with 3-12 months' exposure to Norplant (levonorgestrel subdermal co ntraceptive implant) and to correlate it with bleeding pattern, endome trial histology, and peripheral plasma oestradiol and progesterone con centrations. Endometrial biopsies were processed routinely and section s immunostained using anti-CD34 antibody to identify vascular endothel ial cells. Menstrual record card data were analysed using World Health Organization definitions. The mean microvascular density (+/- SEM) fo r control samples was 186 +/- 8 vessels/mm2, and there were no signifi cant differences across the cycle. Norplant user's endometrial microva scular density was significantly elevated above controls (294 +/- 18 v essels/mm2, P = 3.36 x 10(-8)). Endometrial microvascular density in N orplant users did not correlate with oestrogen concentrations prior to biopsy, bleeding patterns or endometrial histology. The results from this study show that women receiving Norplant have significantly incre ased endometrial microvascular density compared to controls. Another f inding from this study was that bleeding in Norplant users often occur red from thin atrophic endometrium. These results provide new insights into the physiological mechanisms that may be involved in progestogen -induced endometrial bleeding.