Contraception: Endometrial microvascular density during the normal menstrual cycle and following exposure to long-term levonorgestrel

Abstract

The mechanisms that underlie progestogen-induced endometrial breakthrough bleeding are poorly understood. The aim of the present study was to quantify endometrial microvascular density in 54 controls and 42 women with 3–12 months' exposure to Norplant (levonorgestrel subdermal contraceptive implant) and to correlate it with bleeding pattern, endometrial histology, and peripheral plasma oestradiol and progesterone concentrations. Endometrial biopsies were processed routinely and sections immunostained using anti-CD34 antibody to identify vascular endothelial cells. Menstrual record card data were analysed using World Health Organization definitions. The mean microvascular density (± SEM) for control samples was 186 ± 8 vessels/mm², and there were no significant differences across the cycle. Norplant user's endometrial microvascular density was significantly elevated above controls (294 ± 18 vessels/mm², P = 3.36 x 10⁻⁸). Endometrial microvascular density in Norplant 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 increased endometrial microvascular density compared to controls. Another finding from this study was that bleeding in Norplant users often occurred from thin atrophic endometrium. These results provide new insights into the physiological mechanisms that may be involved in progestogen-induced endometrial bleeding.