Pelvic versus peripheral steroid levels in postmenopausal patients with and without endometrial hyperplasia or carcinoma.

It is clear that increased exposure to estrogens is an important part of
abnormal endometrial development. Chronic stimulation of the endometrium by
estrogens results in increased proliferation of endometrial glands, which will
cause the development of hyperplasia. Endometrial hyperplasia can be a
precursor stage of endometrial carcinoma. The steroids in the blood produced by
the ovary enter the systemic circulation through the ovarian veins towards the
caval vein or through the para-uterine vessels towards the uterine vein,
passing the uterus on their way. The latter may result in a individual estrogen
environment around the uterus. Previous studies found that during the
follicular and luteal phase the estradiol concentrations in the blood of the
parauterine vessels are significantly higher than the concentrations in the
peripheral circulation. The progesteron levels are also significantly
different. In postmenopausal women a higher concentration of androgens
(androstenedione) was found in the ovarian venous plexus compared to the
peripheral circulation. Androgens play an important role in the estradiol
synthesis. More than 40% of endometrial carcinoma incidence can be attributed
to excess body wight. This is due to peripheral conversion of androgens to
estrogens in adipose tissue by the aromatase enzym. With the knowledge that
estrogen levels in the para-uterine vessels can vary strongly, we hypothesize
that women with endometrial hyperplasia and endometrial carcinoma may have
aberrant local steroid levels around the uterus.

The aim of the study is to investigate the local levels of steroid-hormones
compared to the peripheral levels in postmenopausal patients with endometrial
hyperplasia, endometrial carcinoma and postmenopausal women without these
diseases. This will give more information of the local steroid hormone
concentrations and its relations to the development of endometrial
abnormalities. The secondairy objective is to look at the relation of the
results with patients* Body Mass Index (BMI).

The study will be a case-control study with invasive measurements. The
inclusion of patients will be planned between 01-05-2010 and 01-10-2010. The
treating specialist will inform patients in whom an abdominal hysterectomy with
bilateral oophorectomy is planned. Information about this study will be given
verbally and with the aid of an information leaflet. Patients are free to
participate in the study and their choice will not influence the treatment they
receive. Patients will have time to make the decision to participate or not.

In case of participation, we take 3 blood samples during surgery (for details
see chapter 7):
1) one sample of the infundibolopelvic vein
2) one sample of the parauterine vein
3) one sample of the intravenous infusion.

Serum steroid levels will be compared to the pathological outcome. The study
participation ends when the final pathology results are known. There is no need
for follow-up.

Three blood samples (2-3ml) will be taken during general anaesthesia. There are
no extra risks for patients participating in this study. The goal of this study
is to find more information about the development of endometrial abnormalities.