there exist intra & inter patient variability of 17β-HSD-1 and other enzymes involved in the local generation of estrogens
Bron
Verkorte titel
Aandoening
- Baarmoeder-, bekken- en ligamentum-latumafwijkingen
Aandoening
endometriosis local estrogen metabolism intracrinology
Betreft onderzoek met
Ondersteuning
Onderzoeksproduct en/of interventie
- Overige
Uitkomstmaten
Primaire uitkomstmaten
Clinical data (via a case report form) and epidemiological, life style and symptoms data (via a questionnaire) will be collected prospectively. Blood samples will be taken before treatment. During surgery endometrial and endometriosis biopsies will be collected. Serum and tissue will be analysed for the steroid profile (LCMS). Biopsies will be assessed for the levels of the enzymes involved in the local estrogen generation. Steroid metabolism data will be correlated with clinical characteristics and symptomatology in each subject.
Achtergrond van het onderzoek
Endometriosis is characterised by the presence of endometrial tissue outside the uterine cavity. This condition affects 10% of women of reproductive age and is associated with a number of distressing symptoms such as dysmenorrhoea, dyspareunia, pelvic pain and sub-fertility, with important economic impacts on the society.
In a recent study, we showed the endometriotic tissue (ectopic) is capable of producing local higher levels of 17β-estradiol than the endometrium located inside the uterus (eutopic) because of high level of the enzyme 17β-hydroxysteroid-dehydrogenase type 1 (17β-HSD-1) that converts the low-potent estrone into the high-potent 17β-estradiol. In addition to our findings, also others showed that 17β-HSD-1 can be a potential drug target for endometriosis.
Compounds targeting the 17β-HSD type 1 enzyme are close to the first human trials.
To best design future human trials it is important to characterise the intra & inter patient variability of 17β-HSD-1 and other enzymes involved in the local generation of estrogens (e.g. intracrinology).
Objectives: 1) Chart the intracrine metabolism in women with endometriosis, e.g.: determine the steroid content in endometriosis lesions and in the serum; assess the levels of the intracrine enzymes (mRNA and protein) in endometriosis lesions. 2) Chart the intracrine metabolism (as described in Objective 1) in lesions from distinct location in the same patient.
3) Chart the intracrine metabolism (as described in Objective 1) in the normal endometrium of patients with endometriosis and controls. As secondary objectives, intracrine features will be correlated with additional clinical and radiology characteristics (obtained through standard care) and metabolite profile (such as steroids, inflammatory mediators) in urine and peritoneal fluid. Three hundreds (300) patients and 100 control subjects will be recruited for a total of 400 study subjects.
Doel van het onderzoek
there exist intra & inter patient variability of 17β-HSD-1 and other enzymes involved in the local generation of estrogens
Onderzoeksopzet
non applicable
Onderzoeksproduct en/of interventie
Blood (10 mL), urine (10 mL) and peritonel fluid sampling (10 mL) prior to standard care (e.g. surgery, medical treatment). Completing a questionnaire about life-style. Obtaining an eutopic endometrial sample and a control (without disease) peritoneal sample from both patients and controls (sample from endometriosis tissue will be obtained from rest surgical material).
Publiek
GROW-School for Oncology and Developmental Biology<br>
Maastricht University Medical Centre<br>
P. Debyelaan 25
Andrea Romano
Maastricht 6202 AZ
The Netherlands
+31 (0)43 3881286
a.romano@maastrichtuniversity.nl
Wetenschappelijk
GROW-School for Oncology and Developmental Biology<br>
Maastricht University Medical Centre<br>
P. Debyelaan 25
Andrea Romano
Maastricht 6202 AZ
The Netherlands
+31 (0)43 3881286
a.romano@maastrichtuniversity.nl
Leeftijd
Belangrijkste voorwaarden om deel te mogen nemen (Inclusiecriteria)
Cases:
- Being older than 18 year
- Diagnosis of endometriosis (laparoscopically confirmed)
- Being scheduled for elective laparoscopic (or laparotomy) surgery for endometriosis
- Not taking hormonal medications in the previous three months
- Subjects must have signed an approved informed consent
Controls:
- Being older than 18 year
- Being premenopausal
- Having no prior diagnosis of endometriosis
- Not taking hormonal medications in the previous three months
- Being scheduled for any gynaecological surgery like for tubal ligation, for a benign uterine disease, for diagnosis, for laparoscopic hysterectomy and bilateral adnexectomy
- Subjects must have signed an approved informed consent
Belangrijkste redenen om niet deel te kunnen nemen (Exclusiecriteria)
Cases:
- Being younger than 18 year
- Diagnosis of atypical hyperplasia, other types of cancer
- Previous diagnosis of endometrial carcinoma
- Being under hormonal medication during the three months preceding the sampling
- Pregnancy
- Inability to approve the informed consent form
Controls:
- Being younger than 18 year
- Being diagnosed with a benign ovarian diseases
- Being diagnosed with any malignancy
- Previous diagnosis of endometriosis
- Being under hormonal medication during the three months preceding the sampling
- Pregnancy
- Inability to approve the informed consent form
Opzet
Deelname
Voornemen beschikbaar stellen Individuele Patiënten Data (IPD)
Postbus 5800
6202 AZ Maastricht
043 387 6009
secretariaat.metc@mumc.nl
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Register | ID |
---|---|
NTR-new | NL7024 |
NTR-old | NTR7491 |
CCMO | NL65333.068.18 |