Skip Navigation

This Article
Right arrow Full Text (PDF )
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (114)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Rogers, P. A.W.
Right arrow Articles by Affandi, B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Rogers, P. A.W.
Right arrow Articles by Affandi, B.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Human Reproduction, Vol. 8, No. 9, pp. 1396-1404, 1993
© 1993 European Society of Human Reproduction and Embryology

research-article

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

Peter A.W. Rogers1, Chak L. Au3 and Biran Affandi2

Department of Obstetrics and Gynaecology, Monash University, Monash Medical Centre 246 Clayton Road, Clayton, Victoria, 3168 Australia 2Study Group on Human Reproduction, University of Indonesia Klinik Raden Saleh, Jalan Raden Saleh 49, Jakarta 10330, Indonesia

Correspondence: 1To whom correspondence should be addressed

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.

Key words: endometrial bleeding/endometrium/immunohisto-chemistry/microvascular density/Norplant

3Present address: Department of Physiology, Chinese University of Hong Kong, Shatin, New Territories, Hong Kong


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Reproductive SciencesHome page
C. J. Lockwood, G. Krikun, M. Hickey, S. J. Huang, and F. Schatz
Decidualized Human Endometrial Stromal Cells Mediate Hemostasis, Angiogenesis, and Abnormal Uterine Bleeding
Reproductive Sciences, February 1, 2009; 16(2): 162 - 170.
[Abstract] [PDF]

Home page
 Hum ReprodHome page
S. Labied, C. Galant, M. Nisolle, S. Ravet, C. Munaut, E. Marbaix, J.-M. Foidart, and F. Frankenne
Differential elevation of matrix metalloproteinase expression in women exposed to levonorgestrel-releasing intrauterine system for a short or prolonged period of time
Hum. Reprod., January 1, 2009; 24(1): 113 - 121.
[Abstract] [Full Text] [PDF]

Home page
 Hum ReprodHome page
R. Stephanie, S. Labied, S. Blacher, F. Frankenne, C. Munaut, V. Fridman, A. Beliard, J.-M. Foidart, and M. Nisolle
Endometrial vessel maturation in women exposed to levonorgestrel-releasing intrauterine system for a short or prolonged period of time
Hum. Reprod., December 1, 2007; 22(12): 3084 - 3091.
[Abstract] [Full Text] [PDF]

Home page
 ReproductionHome page
N. B Morison, J. Zhang, T. J Kaitu'u-Lino, I. S Fraser, and L. A Salamonsen
The long-term actions of etonogestrel and levonorgestrel on decidualized and non-decidualized endometrium in a mouse model mimic some effects of progestogen-only contraceptives in women
Reproduction, January 1, 2007; 133(1): 309 - 321.
[Abstract] [Full Text] [PDF]

Home page
 ReproductionHome page
V Bourlev, N Volkov, S Pavlovitch, N Lets, A Larsson, and M Olovsson
The relationship between microvessel density, proliferative activity and expression of vascular endothelial growth factor-A and its receptors in eutopic endometrium and endometriotic lesions.
Reproduction, September 1, 2006; 132(3): 501 - 509.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
H. N. Jabbour, R. W. Kelly, H. M. Fraser, and H. O. D. Critchley
Endocrine Regulation of Menstruation
Endocr. Rev., February 1, 2006; 27(1): 17 - 46.
[Abstract] [Full Text] [PDF]

Home page
 Hum ReprodHome page
P.A.W. Rogers, F. Martinez, J.E. Girling, F. Lederman, L. Cann, E. Farrell, F. Tresserra, and N. Patel
Influence of different hormonal regimens on endometrial microvascular density and VEGF expression in women suffering from breakthrough bleeding
Hum. Reprod., December 1, 2005; 20(12): 3341 - 3347.
[Abstract] [Full Text] [PDF]

Home page
 Hum ReprodHome page
B. Moller, M. Ronnerdag, G. Wang, V. Odlind, and M. Olovsson
Expression of vascular endothelial growth factors and their receptors in human endometrium from women experiencing abnormal bleeding patterns after prolonged use of a levonorgestrel-releasing intrauterine system
Hum. Reprod., May 1, 2005; 20(5): 1410 - 1417.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
E. A. Pritts, I. P. Ryan, M. D. Mueller, D. I. Lebovic, J. L. Shifren, C. J. Zaloudek, A. P. Korn, P. D. Darney, and R. N. Taylor
Angiogenic Effects of Norplant Contraception on Endometrial Histology and Uterine Bleeding
J. Clin. Endocrinol. Metab., April 1, 2005; 90(4): 2142 - 2147.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
C. J. Lockwood, P. Kumar, G. Krikun, S. Kadner, P. Dubon, H. Critchley, and F. Schatz
Effects of Thrombin, Hypoxia, and Steroids on Interleukin-8 Expression in Decidualized Human Endometrial Stromal Cells: Implications for Long-Term Progestin-Only Contraceptive-Induced Bleeding
J. Clin. Endocrinol. Metab., March 1, 2004; 89(3): 1467 - 1475.
[Abstract] [Full Text] [PDF]

Home page
 Hum ReprodHome page
B.A. Roopa, A. Loganath, and K. Singh
The effect of a levonorgestrel-releasing intrauterine system on angiogenic growth factors in the endometrium
Hum. Reprod., September 1, 2003; 18(9): 1809 - 1819.
[Abstract] [Full Text] [PDF]

Home page
 Hum ReprodHome page
M. Hickey, G. Pillai, J.M. Higham, M. Sullivan, D. Horncastle, D. Doherty, and G. Stamp
Changes in endometrial blood vessels in the endometrium of women with hormone replacement therapy-related irregular bleeding
Hum. Reprod., May 1, 2003; 18(5): 1100 - 1106.
[Abstract] [Full Text] [PDF]

Home page
 Hum ReprodHome page
J.B. Laoag-Fernandez, T. Maruo, P. Pakarinen, I.M. Spitz, and E. Johansson
Effects of levonorgestrel-releasing intra-uterine system on the expression of vascular endothelial growth factor and adrenomedullin in the endometrium in adenomyosis
Hum. Reprod., April 1, 2003; 18(4): 694 - 699.
[Abstract] [Full Text] [PDF]

Home page
 Mol Hum ReprodHome page
J. M. Borthwick, D. S. Charnock-Jones, B. D. Tom, M. L. Hull, R. Teirney, S. C. Phillips, and S. K. Smith
Determination of the transcript profile of human endometrium
Mol. Hum. Reprod., January 1, 2003; 9(1): 19 - 33.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
J. M. Hastings, D. R. Licence, G. J. Burton, D. S. Charnock-Jones, and S. K. Smith
Soluble Vascular Endothelial Growth Factor Receptor 1 Inhibits Edema and Epithelial Proliferation Induced by 17{beta}-Estradiol in the Mouse Uterus
Endocrinology, January 1, 2003; 144(1): 326 - 334.
[Abstract] [Full Text] [PDF]

Home page
 Hum ReprodHome page
C. J. McGavigan, P. Dockery, V. Metaxa-Mariatou, D. Campbell, C. J.R. Stewart, I. T. Cameron, and S. Campbell
Hormonally mediated disturbance of angiogenesis in the human endometrium after exposure to intrauterine levonorgestrel
Hum. Reprod., January 1, 2003; 18(1): 77 - 84.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
A. L. Niklaus, J. S. Babischkin, G. W. Aberdeen, G. J. Pepe, and E. D. Albrecht
Expression of Vascular Endothelial Growth/Permeability Factor by Endometrial Glandular Epithelial and Stromal Cells in Baboons during the Menstrual Cycle and after Ovariectomy
Endocrinology, October 1, 2002; 143(10): 4007 - 4017.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
C. J. Lockwood, G. Krikun, A. B. C. Koo, S. Kadner, and F. Schatz
Differential Effects of Thrombin and Hypoxia on Endometrial Stromal and Glandular Epithelial Cell Vascular Endothelial Growth Factor Expression
J. Clin. Endocrinol. Metab., September 1, 2002; 87(9): 4280 - 4286.
[Abstract] [Full Text] [PDF]

Home page
 Hum ReprodHome page
M. Hickey and I.S. Fraser
Surface vascularization and endometrial appearance in women with menorrhagia or using levonorgestrel contraceptive implants. Implications for the mechanisms of breakthrough bleeding
Hum. Reprod., September 1, 2002; 17(9): 2428 - 2434.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
G. Krikun, H. Critchley, F. Schatz, L. Wan, R. Caze, R. N. Baergen, and C. J. Lockwood
Abnormal Uterine Bleeding during Progestin-Only Contraception May Result from Free Radical-Induced Alterations in Angiopoietin Expression
Am. J. Pathol., September 1, 2002; 161(3): 979 - 986.
[Abstract] [Full Text] [PDF]

Home page
 Hum ReprodHome page
C. E. Gargett, F. Lederman, B. Heryanto, L. S. Gambino, and P. A.W. Rogers
Focal vascular endothelial growth factor correlates with angiogenesis in human endometrium. Role of intravascular neutrophils
Hum. Reprod., June 1, 2001; 16(6): 1065 - 1075.
[Abstract] [Full Text] [PDF]

Home page
 Mol Hum ReprodHome page
B. Moller, C. Rasmussen, B. Lindblom, and M. Olovsson
Expression of the angiogenic growth factors VEGF, FGF-2, EGF and their receptors in normal human endometrium during the menstrual cycle
Mol. Hum. Reprod., January 1, 2001; 7(1): 65 - 72.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
R. Runic, F. Schatz, L. Wan, R. Demopoulos, G. Krikun, and C. J. Lockwood
Effects of Norplant on Endometrial Tissue Factor Expression and Blood Vessel Structure
J. Clin. Endocrinol. Metab., October 1, 2000; 85(10): 3853 - 3859.
[Abstract] [Full Text]

Home page
 Hum ReprodHome page
M. Wahab, J. Thompson, and F. Al-Azzawi
Effect of different cyclical sequential progestins on endometrial vascularity in postmenopausal women compared with the natural cycle: a morphometric analysis
Hum. Reprod., October 1, 2000; 15(10): 2075 - 2081.
[Abstract] [Full Text] [PDF]

Home page
 Hum ReprodHome page
M. Hickey, D. Dwarte, and I.S. Fraser
Superficial endometrial vascular fragility in Norplant users and in women with ovulatory dysfunctional uterine bleeding
Hum. Reprod., July 1, 2000; 15(7): 1509 - 1514.
[Abstract] [Full Text] [PDF]

Home page
 Hum ReprodHome page
M. Hickey, C. Carati, F. Manconi, B.J. Gannon, D. Dwarte, and I.S. Fraser
The measurement of endometrial perfusion in Norplant users: a pilot study
Hum. Reprod., May 1, 2000; 15(5): 1086 - 1091.
[Abstract] [Full Text] [PDF]

Home page
 Hum ReprodHome page
G. Kohnen, S. Campbell, M. D. Jeffers, and I. T. Cameron
Spatially regulated differentiation of endometrial vascular smooth muscle cells
Hum. Reprod., February 1, 2000; 15(2): 284 - 292.
[Abstract] [Full Text] [PDF]

Home page
 Hum ReprodHome page
A. Faundes, F. Alvarez, V. Brache, L. Cochon, A. S. Tejada, and A. Moo-Young
Correlation of endocrine profiles with bleeding patterns during use of Nestorone(R) contraceptive implants
Hum. Reprod., December 1, 1999; 14(12): 3013 - 3017.
[Abstract] [Full Text] [PDF]

Home page
 Hum ReprodHome page
A. M. Macpherson, D. F. Archer, S. Leslie, D.S. Charnock-Jones, W.K. Makkink, and S. K. Smith
The effect of etonogestrel on VEGF, oestrogen and progesterone receptor immunoreactivity and endothelial cell number in human endometrium
Hum. Reprod., December 1, 1999; 14(12): 3080 - 3087.
[Abstract] [Full Text] [PDF]

Home page
 Hum ReprodHome page
C.E. Gargett, F.L. Lederman, T.M. Lau, N.H. Taylor, and P.A.W. Rogers
Lack of correlation between vascular endothelial growth factor production and endothelial cell proliferation in the human endometrium
Hum. Reprod., August 1, 1999; 14(8): 2080 - 2088.
[Abstract] [Full Text] [PDF]

Home page
 Hum ReprodHome page
B. Vailhe, J. Dietl, M. Kapp, B. Toth, and P. Arck
Increased blood vessel density in decidua parietalis is associated with spontaneous human first trimester abortion
Hum. Reprod., June 1, 1999; 14(6): 1628 - 1634.
[Abstract] [Full Text] [PDF]

Home page
 Hum ReprodHome page
M. Hickey, M. Simbar, R. Markham, L. Young, F. Manconi, P. Russell, and I.S. Fraser
Changes in vascular basement membrane in the endometrium of Norplant users
Hum. Reprod., March 1, 1999; 14(3): 716 - 721.
[Abstract] [Full Text] [PDF]

Home page
 Mol Hum ReprodHome page
T. M. Lau, B. Affandi, and P. A.W. Rogers
The effects of levonorgestrel implants on vascular endothelial growth factor expression in the endometrium
Mol. Hum. Reprod., January 1, 1999; 5(1): 57 - 63.
[Abstract] [Full Text] [PDF]

Home page
 Biol. Reprod.Home page
T. Sandberg,, B. Casslén,, B. Gustavsson,, and T. J. Benraad
Human Endothelial Cell Migration Is Stimulated by Urokinase Plasminogen Activator:Plasminogen Activator Inhibitor 1 Complex Released from Endometrial Stromal Cells Stimulated with Transforming Growth Factor ß1; Possible Mechanism for Paracrine Stimulation of Endometrial Angiogenesis
Biol Reprod, October 1, 1998; 59(4): 759 - 767.
[Abstract] [Full Text]

Home page
 J. Clin. Endocrinol. Metab.Home page
R. Runic, F. Schatz, L. Krey, R. Demopoulos, S. Thung, L. Wan, and C. J. Lockwood
Alterations in Endometrial Stromal Cell Tissue Factor Protein and Messenger Ribonucleic Acid Expression in Patients Experiencing Abnormal Uterine Bleeding While Using Norplant-2 Contraception
J. Clin. Endocrinol. Metab., June 1, 1997; 82(6): 1983 - 1988.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.