This study aimed to investigate the effects of the subdermal levonorgestrel contraceptive implant Norplant(R) on endometrial vascular density at different durations of exposure, and the relationship between endometrial histology, vascular density, and bleeding patterns. A prospective controlled trial of Norplant implant users compared endometrial vascular density in biopsies taken before and after Norplant implant insertion. A total of 34 women with regular menstrual cycles requesting long-term contraception were recruited at the Sydney Centre for Reproductive Health Research, Australia. A significant increase in mean endometrial microvascular density was observed from as early as 3 weeks after insertion of Norplant implants. Vascular density was increased from a control secretory phase value of 189.6 ( 7.0 vessels/mm(2) (+/-SEM) to 253.80 +/- 7 vessels/mm(2) at 2-13 weeks of Norplant implant exposure (t ratio = 2.08, p = 0.01) and 212.7 +/- 12.9 vessels/mm(2) at 14-42 weeks of exposure (t ratio = 2.03, p = 0.02). In those with atrophic endometrium, or in whom myometrium and basalis only were found in biopsies (20 of 66, 30%), mean endometrial vascular density was increased at 273.1 +/- 16.2 vessels/mm(2) compared with 210.9 +/- 11.7 vessels/mm(2) in other histological groups (F ratio = 9.74, p = 0.0028), Bleeding and spotting in the previous 30 days were less common in those with this histological appearance at a mean of 4.95 days compared with 8.22 days. This is the first study to assess endometrial vascular density in the early months of Norplant implant use. The findings suggest that the endometrial vasculature is profoundly altered in the early months of Norplant implant exposure when bleeding problems are most common. (C) 1999 Elsevier Science Inc. All rights reserved.