Surface vascularization and endometrial appearance in women with menorrhagia or using levonorgestrel contraceptive implants. Implications for the mechanisms of breakthrough bleeding.
BACKGROUND
Women using progestogen-only contraceptives are commonly troubled by irregular bleeding. Endometrial vessel breakdown and repair is thought to be locally regulated under the indirect influence of sex steroids. Most information about endometrial vessels is derived from blind biopsies taken in an outpatient setting. Hysteroscopy allows in-vivo observation of the whole endometrial surface, including vessel morphology, distribution and areas of bleeding, as well as information about non-vascular structures that may not be accessible from biopsies.


METHODS
Hysteroscopies were performed on 34 women using the levonorgestrel contraceptive implant system (Norplant(TM)) and in a comparison group of 20 women complaining of menorrhagia due to ovulatory dysfunctional bleeding. The images were captured and vascular appearances assessed using image analysis.


RESULTS
The percentage of the superficial endometrium covered with blood vessels was found to be significantly greater in Norplant users compared with the comparison group (P = 0.0006). More superficial vessels were seen in those with recent frequent or prolonged bleeding and spotting (P < 0.0001). In Norplant users, but not in the comparison group, superficial vascular distribution was predominantly patchy (P < 0.0001). Unusual vascular appearances classified as 'neovascular' (P < 0.0001) and 'mosaic' (P < 0.0001) patterns were commonly seen in Norplant users but not in the comparison group. The hysteroscopic appearance of the endometrial epithelium, glands and stroma also differed between Norplant users and women with menorrhagia. Apparent shedding of the superficial endometrium was commonly seen by hysteroscopy in Norplant users during a bleeding episode (P < 0.0001). Prominent gland openings with thick mucus were commonly seen in Norplant users and small sessile polyps were seen in six cases.


CONCLUSIONS
These hysteroscopic observations provide further evidence that exposure to progestogens alters the superficial endometrial vasculature and may interfere with angiogenesis.
Department of Obstetrics and Gynaecology, University of Western Australia King Edward Memorial Hospital, 374 Bagot Road, Subiaco, WA 6008, Australia. mhickey@obsgyn.uwa.edu.au
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Hickey
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Fraser
D000328:Adult; D001808:Blood Vessels / Q000473:pathology; D003271:Contraceptive Agents, Female / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D004343:Drug Implants; D004717:Endometrium / Q000098:blood supply* / Q000187:drug effects / Q000473:pathology*; D004848:Epithelium / Q000473:pathology; D005260:Female; D006801:Humans; D015907:Hysteroscopy; D016912:Levonorgestrel / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D008595:Menorrhagia / Q000473:pathology*; D011446:Prospective Studies; D014592:Uterine Hemorrhage / Q000139:chemically induced
D003271:Contraceptive Agents, Female; D004343:Drug Implants; D016912:Levonorgestrel