Human Reproduction, Vol. 15, No. suppl_3, pp. 78-84, 2000
© 2000 European Society of Human Reproduction and Embryology
Perivascular smooth muscle 
-actin is reduced in the endometrium of women with progestin-only contraceptive breakthrough bleeding
1 Monash University Department of Obstetrics and Gynaecology, Monash Medical Centre 246 Clayton Road, Clayton, Victoria, 3168, Australia 2 Department of Obstetrics and Gynaecology, Faculty of Medicine, University of Indonesia Jakarta, 10430, Indonesia
Correspondence: 3To whom correspondence should be addressed at: Monash University Department of Obstetrics and Gynaecology, Monash Medical Centre, 246 Clayton Road, Clayton, Victoria, 3168, Australia. E-mail: peter.rogers{at}med.monash.edu.au
It has been shown that the endometrium of women using progestin-only contraceptives has increased vascular fragility, although the structural basis for this weakness is unknown, as is its role in breakthrough bleeding (BTB). Perivascular cells such as pericytes and vascular smooth muscle cells surround capillaries during the maturation process following angiogenesis,and act to strengthen and stabilize the vessels. The aim of the present study wasto quantify endometrial perivascular smooth muscle 
-actin (SMA) expression in women using Norplant® with and without BTB problems, and compare it to controls. Using immunohistochemical techniques, vessels were classified as level 0, 1 or 2 depending on whether perivascular SMA was absent, discontinuous or continuous. In 15 controls the subepithelial plexus had significantly more level 0 vessels than either the functionalis or basalis (61 ± 4 versus 31 ± 6 and 37 ± 4%, P = 0.0006 and P = 0.0007 respectively). In contrast the functionalis and basalis had significantly more level 2 vessels than the subepithelial plexus (20 ± 3 and 23 ± 2 compared to 4 ± 1%, P = 0.0005 and P – 0.000 respectively). The major finding of the study was that in Norplant users, where the relatively atrophic endometrium cannot be divided into different regions, women with BTB problems (n = 20) had significantly more level 0 vessels than those with reduced bleeding (n = 17) (60 ± 4 versus 46 ± 4percnt;, P = 0.0302). Norplant users with BTB problems also had a non-significant reduction in level 2 vessels compared to women without bleeding problems (4 ± 2 versus 11 ± 4percnt;, P equals; 0.0667). These results demonstrate that perivascular SMA is reduced around the endometrial vessels of Norplant users with BTB compared to those with no bleeding problems, and strongly support the concept that reduced vascular structural integrity plays a key role in endometrial BTB.
Key words:
breakthrough bleeding/endometrium/Norplant®/smooth muscle -actin/vascular fragility
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