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Purpose: Neo-angiogenesis is necessary for adhesion and invasiveness of endometriotic lesions in women affected by endometriosis. VEGF is one of the major components of angiogenesis and is part of the major pathway TF-PAR-2-VEGF that leads to neo-angiogenesis. SP1 is a transcriptional factor that has lately been studied for its crucial role in angiogenesis, via a distinct pathway. We hypothesize that by blocking angiogenetic pathways we can repress endometriotic lesions. GnRH-agonists are routinely used, especially pre-operatively, in endometriosis. It would be interesting to clarify which angiogenetic pathways are affected and pave the way for further research over anti-angiogenetic effects on endometriosis.
Methods: We used qRT-PCR to study mRNA expression levels of TF, PAR-2, VEGF and SP1 in endometriotic tissues of women who underwent surgery for endometriosis and received GnRH-a [leuprolide acetate] preoperatively.
The subjects in this study were women of reproductive age. From September 2015 to December 2022, sixty women with known endometriosis [stage 2 and 3], were recruited. Their mean age was 38 years. They were nulliparous and had a mean BMI of 27 kg/m2. The ovarian endometrioma, present in all the participants, was diagnosed by ultrasonography and/or magnetic resonance imaging.
This was a prospective randomized follow up study with analysis of ovarian samples derived from GnRH agonists-treated and non-treated women before surgery. The randomization was performed by accessing a central internet-based randomization program. The random allocation sequence and the assignment of the participants to interventions were made by 2 of the authors [A.K. and S.K].
After enrollment, patients were divided into 2 groups . During laparoscopy, biopsy specimens of the ovarian endometrioma were collected. The staging of endometriosis was based on the rASRM classification system. In group B, surgery was performed during the proliferative phase of the menstrual cycle. All biopsy specimens were collected in accordance with the guidelines of the Declaration of Helsinki and with the approval of the ethical committee of the General University Hospital of Patras. Informed consent was obtained from all women.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| GnRH-a + | Active Comparator | Group A [GnRHa+] consisted of 30 women with a mean age of 35.5 years and a mean BMI of 27 kg/m2. Seventeen of them were stage 2 and 13 were stage 3 endometriosis. They received GnRH-a [leuprolide acetate] for a period of 3 months prior to surgery, whereas they had not received any hormonal treatment within the 12 months before the surgical procedure. |
|
| GnRH-a - | No Intervention | Group B [GnRHa-] consisted of 30 patients with a mean age of 38 years and a mean BMI of 27 kg/m2. Sixteen of them had stage 2 and 14 had stage 3 endometriosis. They did not receive GnRH-a treatment before operation. In addition, no treatment with oral contraceptives or other therapy was administered within 12 months prior to surgery. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Leuprolide Acetate | Drug | Leuprolide acetate was administered 3 months before laparoscopy in women of group A. |
|
| Measure | Description | Time Frame |
|---|---|---|
| VEGF | VEGF levels with or without leuprolide acetate treatment | 3 months |
| Tissue factor | Tissue factor levels with or without leuprolide acetate treatment | 3 months |
| PAR-2 | PAR-2 levels with or without leuprolide acetate treatment | 3 months |
| SP1 | SP1 levels with or without leuprolide acetate treatment | 3 months |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Patras University School of Medicine | Patra | Peloponnese | 26504 | Greece | ||
| Tottori University Faculty of Medicine |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38639888 | Derived | Filindris T, Papakonstantinou E, Keramida M, Panteris E, Kalogeropoulos S, Georgopoulos N, Taniguchi F, Adonakis G, Harada T, Kaponis A. The effect of GnRH-a on the angiogenesis of endometriosis. Hormones (Athens). 2024 Sep;23(3):509-515. doi: 10.1007/s42000-024-00559-6. Epub 2024 Apr 19. |
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Results of this study
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| ID | Term |
|---|---|
| D004715 | Endometriosis |
| ID | Term |
|---|---|
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
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| ID | Term |
|---|---|
| D016729 | Leuprolide |
| ID | Term |
|---|---|
| D007987 | Gonadotropin-Releasing Hormone |
| D010906 | Pituitary Hormone-Releasing Hormones |
| D007028 | Hypothalamic Hormones |
| D036361 | Peptide Hormones |
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This was a prospective randomized follow up study with analysis of ovarian samples derived from GnRH agonists-treated and non-treated women before surgery. The randomization was performed by accessing a central internet-based randomization program. The random allocation sequence and the assignment of the participants to interventions were made by 2 of the authors [A.K. and S.K].
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| Yonago |
| Tottori |
| 683-8503 |
| Japan |
| D000091662 | Genital Diseases |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D009479 | Neuropeptides |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D009842 | Oligopeptides |
| D009419 | Nerve Tissue Proteins |
| D011506 | Proteins |