Norwegian Adenomyosis Study: Pathophysiology, Peristalsis, Expression Profiling and Diagnosis, Part 2
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- Sensitivity and specificity of biopsies for adenomyotic tissue in percent (%)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 30 Years 至 50 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •postmenopausal women,
- •pregnancy
- •gynecological cancer
- •GnRH analog therapy or systemic hormone therapy in the last three months prior to hysterectomy
- •junctional zone not identifiable
结局指标
主要结局
Sensitivity and specificity of biopsies for adenomyotic tissue in percent (%)
时间窗: At time of hysterectomy
Sensitivity and specificity of ultrasound guided myometrial biopsies for adenomyotic tissue
次要结局
- difference hormone serum-levels in fold(at time of hysterectomy)
- multiple comparison of gene expression, measured in fold(at time of biopsy taking)
- Serum levels of prolactin in mU/L(at time of hysterectomy)
- Serum level of ER, in nmol/L(at time of hysterectomy)
- Serum levels of FSH in U/L(at time of hysterectomy)
- Serum levels of LH in U/L(at time of hysterectomy)
- Serum levels of AMH in pmol/L(at time of hysterectomy)
- Frequency of complications related to biopsy taking in percent (%)(through 1 hour after biopsytaking)
研究者
Tina Tellum
MD
Oslo University Hospital