Clinical Trial: Norwegian Adenomyosis Study II: Gene Expression Profiling of Adenomyosis

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Observational

Official Title: Norwegian Adenomyosis Study: Pathophysiology, Peristalsis, Expression Profiling and Diagnosis, Part 2

Brief Summary:

Adenomyosis is characterized by the appearance of endometrial cells in the muscular layer of the uterus. It affects about 15-20% of the female population.

The symptoms of adenomyosis are heavy menstrual bleedings and painful menstruation (dysmenorrhea) and in addition chronic pelvic pain. Subfertility and infertility have been correlated with adenomyosis.

Parity, age and uterine abrasion increase the risk of adenomyosis. Hormonal factors such as local hyperestrogenism and elevated levels of prolactin (PRL) have been identified, but autoimmune and mechanical factors are also hypothesized.

Regarding treatment, the most effective measure is hysterectomy. As this is a very drastic measure in younger women, levonogestrel-releasing intrauterine devices, Gonadotropin releasing hormone (GnRH)-analogues, Danazol, uterine embolization and endometrial ablation have been tried, but studies are few in number, retrospective, and have small sample sizes.

Adenomyosis has so far not been subject to extensive research efforts. The pathogenesis of adenomyosis remains still unclear, there are not many satisfying treatment options and diagnostics include mostly magnetic resonance imaging (MRI) and histology.

The investigators designed a series of 3 studies with a broad approach in understanding adenomyosis. This is part 2.

In this study the investigators take both tissue samples and blood samples that will be investigated in order to understand the basic processes leading to adenomyosis.


Detailed Summary:

Biopsy of focal adenomyosis of the myometrium:

This will be an extension of the NAPPED1-study. The investigators will perform ultrasound-guided transvaginal biopsies of the myometrium and collect venous blood samples.

As recent studies have suggested abnormalities in the regulation of specific genes in the development of adenomyosis, the investigators want to investigate differentially expressed genes in adenomyosis compared to eutopic endometrium. Using microarrays, the investigators can simultaneously screen differences in expression of thousands of genes in samples from the two groups. Profiling studies performed on endometrium of healthy individuals and of endometriosis show results that enable identification of biological processes and molecular mechanisms. Expression profiles can be used to identify molecular targets for therapeutic purposes. There are some very interesting studies that investigate drug treatment on a molecular level e.g. the effect of Danazol treatment on eutopic and ectopic endometrial tissue, but intramural adenomyosis has not been subject to gene profiling yet.

Tissue samples can be easily obtained after hysterectomy, but those samples will only represent older women, and cannot be used for consecutive monitoring of biochemical effects of treatment, as the uterus is removed. In order to investigate the pathophysiology of adenomyosis in younger women, and compare it to those in older individuals, as well as to evaluate effects of treatment, it is necessary to be able to obtain in-vivo samples.

The plan is therefore to take transvaginal, ultrasound-guided biopsy-samples from the uterus (myometrium) of all included patients at the beginning of their surgery, when the patient is under full anesthesia.
Sponsor: Oslo University Hospital

Current Primary Outcome: Sensitivity and specificity of biopsies for adenomyotic tissue in percent (%) [ Time Frame: At time of hysterectomy ]

Sensitivity and specificity of ultrasound guided myometrial biopsies for adenomyotic tissue


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • multiple comparison of gene expression, measured in fold [ Time Frame: at time of biopsy taking ]
    Expression profile for proliferative and invasive genes in adenomyotic tissue and surrounding stromal cells compared to healthy individuals, in fold
  • Frequency of complications related to biopsy taking in percent (%) [ Time Frame: through 1 hour after biopsytaking ]
  • Serum levels of prolactin in mU/L [ Time Frame: at time of hysterectomy ]
    Serum levels of prolactin
  • Serum level of ER, in nmol/L [ Time Frame: at time of hysterectomy ]
    Serum level of estrogen.
  • Serum levels of FSH in U/L [ Time Frame: at time of hysterectomy ]
    Levels of follicle stimulating hormone.
  • Serum levels of AMH in pmol/L [ Time Frame: at time of hysterectomy ]
    Levels of Anti-Mullerian hormone.
  • Serum levels of LH in U/L [ Time Frame: at time of hysterectomy ]
    Levels of luteinizing hormone.
  • difference hormone serum-levels in fold [ Time Frame: at time of hysterectomy ]
    Comparison of serum-levels of PRL, FSH, AMH, LH and ER in patients with and without adenomyosis


Original Secondary Outcome: Same as current

Information By: Oslo University Hospital

Dates:
Date Received: July 17, 2014
Date Started: July 2014
Date Completion: December 2017
Last Updated: September 14, 2016
Last Verified: September 2016