Local steroid production (intracrinology) in endometriosis - inter & intra patient variability

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).

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.

Prospective cross-sectional multicentre observational case / control study.
Serum and biopsies of ectopic and eutopic endometrium from women diagnosed with
endometriosis (300) and controls (100) will be analysed to assess steroid
levels (LCMS), enzyme levels (mRNA, Immunohistochemistry and enzyme activity -
HPLC) in relation with patient characteristics. Subjects will also fill a
life-style and personal data (including pain symptoms) questionnaire

Some burden is expected for the endometrial and peritoneal control sampling.
These procedures will be however performed under anaesthesia for the
intervention indicated as standard care. The risks associated are low and the
discomfort for the subject is negligible.
The burden for subjects enrolled for the remaining intervention is minimal,
being a blood sampling (10 ml) and peritoneal fluid (performed under
anaesthesia for the intervention indicated as standard care) and urine
sampling. Biopsies from ectopic tissue of patients will be obtained from
rest-surgical material, which does not implicate any intervention/burden for
the patient. The expected benefits are the further drug development for
endometriosis patients. Thus the balance benefits / burdens is positive.