Norwegian Adenomyosis Study II: Gene Expression Profiling of Adenomyosis

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Brief Title

Norwegian Adenomyosis Study II: Gene Expression Profiling of Adenomyosis

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 Description

      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. The safety of comparable procedures has been shown in prior studies,
      but the investigators will further validate the safety of this method. The investigators
      believe that an in-vivo biopsy is a safe measure, and that representative samples of
      adenomyosis can be obtained.

      The challenge with adenomyosis is that it is located intramyometrially. A transcervical
      biopsy will contaminate the sample with eutopic endometria, therefore it is most meaningful
      to take the biopsy transvaginally, but not through the cavity. After obtaining the biopsy
      sample, it will be examined histologically by imprint, to confirm if glandular cells are
      contained where expected. When good routines show a reliable level of specificity, the
      investigators will go further by selecting approximately 10 patients for gene profiling of
      adenomyosis. The investigators will also use endometrial biopsies (Pipelle) from those
      patients to see if there is a difference between intramural adenomyosis and their eutopic
      endometria. Most patients that undergo hysterectomy have taken a pipelle-biopsy routinely.

      The levels of prolactin, Anti-müllerian hormone (AMH), Follicle stimulating hormone (FSH),
      luteinizing hormone (LH) and estrogen will also be taken, in order to determine if the
      severity of adenomyosis is only related to age as shown before, or also to hormonal activity.
    


Study Type

Observational


Primary Outcome

Sensitivity and specificity of biopsies for adenomyotic tissue in percent (%)

Secondary Outcome

 multiple comparison of gene expression, measured in fold

Condition

Adenomyosis

Intervention

Myometrial biopsy

Study Arms / Comparison Groups

 Biopsy: adenomyosis
Description:  Myometrial biopsy Pipelle

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Procedure

Estimated Enrollment

80

Start Date

August 6, 2014

Completion Date

December 1, 2023

Primary Completion Date

November 1, 2022

Eligibility Criteria

        Inclusion Criteria:

        Premenopausal women aged 30 - 50 years old scheduled for vaginal, abdominal or laparoscopic
        total hysterectomy one or more of the following clinical symptoms:

          -  bleeding disorders (menorrhagia, irregular bleeding, hypermenorrhoea),

          -  chronic pelvic pain,

          -  dysmenorrhoea,

          -  or dyspareunia junction zone definable

        Exclusion Criteria:

          -  postmenopausal women,

          -  pregnancy

          -  gynecological cancer

          -  GnRH analog therapy or systemic hormone therapy in the last three months prior to
             hysterectomy

          -  junctional zone not identifiable
      

Gender

Female

Ages

30 Years - 50 Years

Accepts Healthy Volunteers

Accepts Healthy Volunteers

Contacts

Erik Qvigstad, PhD, MD, , 

Location Countries

Norway

Location Countries

Norway

Administrative Informations


NCT ID

NCT02197923

Organization ID

2014/637b


Responsible Party

Principal Investigator

Study Sponsor

Oslo University Hospital

Collaborators

 University of Oslo

Study Sponsor

Erik Qvigstad, PhD, MD, Study Chair, Oslo University Hospital, Ullevål


Verification Date

March 2021