The effect of a levonorgestrel-releasing intrauterine system on angiogenic growth factors in the endometrium.
BACKGROUND
The study aim was to investigate the effects of a levonorgestrel-releasing intrauterine system (LNG-IUS) on the secretion profiles and level of mRNA transcripts for angiogenic growth factors including vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-beta1, basic fibroblast growth factor (bFGF) and endothelial growth factor (EGF) in the endometrium, and their levels in plasma.


METHODS
Blood and endometrial samples were collected from 15 women using LNG-IUS at pre-insertion and at 1, 3, 6 and 12 months following the use of contraception. Using enzyme-linked immunosorbent assay (ELISA) and semi-quantitative reverse transcription techniques, angiogenic growth factors were measured in the plasma and endometrial tissue extracts.


RESULTS
A significant increase in endometrial tissue levels of VEGF at 3 and 6 months (P < 0.007, P < 0.01), TGF-beta1 at 6 and 12 months (P < 0.002, P < 0.007) and bFGF at 1 and 6 months (P < 0.004, P < 0.008) respectively were observed following insertion of LNG-IUS. A corresponding increase in mRNA expression of TGF-beta1 and bFGF were also observed. The LNG-IUS had no effect on endometrial EGF levels. No significant differences were noted in plasma levels of bFGF, EGF and TGF-beta1, while VEGF was not detectable in all plasma samples assayed. A positive correlation was observed between endometrial tissue VEGF and bleeding/spotting days in the reference period (r = 0.705, P < 0.015).


CONCLUSIONS
These results provide the first evidence that more than one angiogenic factor could be implicated in aberrant endometrial angiogenesis resulting in breakthrough bleeding in LNG-IUS acceptors.
Roopa
B A
BA
Department of Obstetrics and Gynaecology, National University Hospital, National University of Singapore, Singapore.
Loganath
Annamalai
A
Singh
Kuldip
K
D000328:Adult; D003271:Contraceptive Agents, Female / Q000008:administration & dosage* / Q000009:adverse effects; D004717:Endometrium / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000097:blood / Q000378:metabolism; D004958:Estradiol / Q000097:blood; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000097:blood / Q000378:metabolism; D006133:Growth Substances / Q000378:metabolism*; D006801:Humans; D007436:Intrauterine Devices, Medicated / Q000009:adverse effects; D016912:Levonorgestrel / Q000008:administration & dosage* / Q000009:adverse effects; D008499:Medical Records; D008597:Menstrual Cycle; D018919:Neovascularization, Physiologic / Q000502:physiology*; D011374:Progesterone / Q000097:blood; D016212:Transforming Growth Factor beta / Q000378:metabolism; D053773:Transforming Growth Factor beta1; D014592:Uterine Hemorrhage / Q000209:etiology / Q000503:physiopathology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D003271:Contraceptive Agents, Female; D006133:Growth Substances; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D011374:Progesterone; D004958:Estradiol; D016912:Levonorgestrel; D004815:Epidermal Growth Factor