 Sök
och bläddra bland Karolinska Institutets avhandlingar |
|
|||||||||||||||||||||||||||||||||||
Doktorsavhandling vid Karolinska Institutet |
||||||||
Mints, MiriamIdiopathic menorrhagia : Studies of angiogenesis and surgical therapyFredagen den 12 december 2003, kl. 9.00. Föreläsningssal R64, Huddinge Universitetssjukhus. Pressmeddelande |
|
|||||||
| ISBN: 91-7349-722-3 | Diss: 03:534 |
Abstract:
Background
Excessive menstrual bleeding, menorrhagia (i.e. > 80 nil loss of blood) is a com-mon
gynecological problem in women of reproductive age, accounting for over 20% of visits to gynecology
outpatient clinics. The disorder may not only cause iron deficiency anemia but also considerable social
discomfort and reduction in the quality of life.
Although commonly
associated with fibroids and carcinoma, approximately 50% of patients with
menorrhagia do not show any evidence of uterine pathology. This suggests a defect in the cellular processes
and regulatory mechanisms of menstruation.
Historically, many women with heavy menstrual bleeding were advised to undergo hysterectomy, which
was the only way of enduring a "cure". Hysterectomy is an effective treatment of menorrhagia, but it is
associated with substantial postoperative morbidity and convalescence. In the early 1990s, endometrial
resection or ablation became a well-established outpatient alternative for the surgical treatment of
menorrhagia.
The aim of this thesis
This work has mainly been focused on two aspects: firstly, the analysis of
transcervical resection of the endometrium (TCRE) as a surgical option for treatment of menorrhagia and,
secondly, on the involvement of the vascular endothelial growth factor (VEGF) family in the regulation of
anglogenesis in the human endometrium in healthy women and those with idiopathic menorrhagia. In
particular, we investigated if the vessel wall anatomy was abnormal and related findings to the expression
of VEGF and VEGF receptors in the blood vessels.
Results The general clinical outcome in the present studies (papers I and II)
showed favorable results with
low peroperative and postoperative complication rates: fluid overload occurred in 4% and perforation in
1% of the patients.
Most of women who underwent TCRE found this surgery acceptable and approximately 80% of these
women have avoided hysterectomy. Second-look hysteroscopy in women after TCRE showed signs of
regenerative endometrium.
In order to determine why the endometrium regenerates and what regulates this process, we have
investigated the expression and distribution of VEGF and its receptors as well as vessel morphology in
normal and menorrhagic endometrium (papers III- V).
Our data suggest an up-regulation of the agonist-receptor pathway of VEGF in idiopathic menorrhagia: the
vascular expression of VEGF-A, VEGFR1, -2, -3 in capillaries was 1.8-, 1.8-, 2.0-, and 1. 6-fold higher,
respectively, in the menorrhagia group.
Since VEGF-A not only stimulates migration and survival of endothelial cells but also induces vascular
permeability, we have addressed this aspect by analyzing of vessel morphology.
We found that vessels in patients with menorrhagia displayed an unusual morphology with focal regions,
gaps. The relative size of the gaps was significantly larger in menorrhagia samples than in controls
(P=0.000002). Moreover, the sizes of the gaps correlated positively to the number of endometrial blood
vessels expressing VEGF-A (P=0.0002) and VEGFR1 (P=0.03).
To our knowledge, this is the first study that demonstrates the presence of endothelial gaps in menorrhagic
endometrium and as a part of a specific disease process.
Conclusions
TCRE provides a minimally invasive technique for treatment of menorrhagia with good
clinical results: about 80% of women have the possibility of avoiding hysterectomy. Therefore,
endometrial resection/ablation should be offered as a surgical option to all women with idiopathic
menorrhagia who have completed their families.
Normal endometrial angiogenesis is perturbed in idiopathic menorrhagia with an up-regulation of the
agonist-receptor pathway of VEGF-A, which leads to anatomical differences in blood vessels, manifested
inter alia as gaps.
Our novel observations may be of significance in order to explain some of the underlying mechanisms that
contribute to idiopathic menorrhagia and will provide novel opportunities for therapeutic intervention in
the future.
Keywords: Menorrhagia, TCRE, endometrium, angiogenesis, VEGF, VEGFR1, -2, -3, gaps.
List of papers
 |
Follow up of hysteroscopic surgery for menorrhagia. Mints M, Radestad A, Rylander E Acta Obstet Gynecol Scand, 1998; 77(4): 435-8 |
|
Ultrasonographic and hysteroscopic follow up after transcervical resection of the endometrium. Mints M, Almstrom H, Rylander E, Radestad A Gynaecological Endoscopy, 1999; 8: 213-7 |
|
Expression of the vascular endothelial growth factor (VEGF) family in human endometrial blood vessels. Mints M, Blomgren B, Falconer C, Palmblad J Scand J Clin Lab Invest, 2002; 62(3): 167-75 |
|
Vascular endothelial growth factor-A and its receptors in endometrial blood vessels in menorrhagia. Mints M, Blomgren B, Falconer C, Fianu-Jonasson A, Palmblad J Manuscript |
|
Vascular abnormalities in the endometrium of menorrhagia patients. Mints M, Zetterberg E, Blomgren B, Falconer C, Rogers R, Palmblad J Manuscript |
