Imaging modalities for the non-invasive diagnosis of endometriosis.
The response of the human endometrium to the ovarian hormones, estrogen and progesterone, has been the focus of decades of research. In order to understand this critical aspect of endometrial physiology, we undertook a genome-wide analysis of transcript abundance and changes in transcript level between normal endometrium in the proliferative and secretory phases of the menstrual cycle. A high-density, oligonucleotide gene array, comprising 60 000 gene targets, was used to define the gene expression profile of proliferative and secretory phase endometrium. Results from the arrays were verified using real-time PCR. The expression levels of 149 transcripts differed significantly between the two phases of the cycle determined by stringent range limits (99.99%), calculated using local variance values. These transcripts include previously documented steroidally responsive genes (such as placental protein 14 and stromelysin-3) and novel transcripts not previously linked to either endometrial physiology or steroid regulation (such as intestinal trefoil factor and a number of expressed sequence tags). Examination of the 5' promoter regions of these genes identified many putative estrogen and progesterone receptor DNA binding domains, suggesting a direct response of these genes to the ovarian hormones.
None of the biomarkers evaluated in this review could be evaluated in a meaningful way and there was insufficient or poor-quality evidence. Laparoscopy remains the gold standard for the diagnosis of endometriosis and using any non-invasive tests should only be undertaken in a research setting.
Signal detection methodology was used to identify the best combination of predictors of long-term exercise adherence in 269 healthy, initially sedentary adults ages 50-65 years. Less educated individuals who were assigned to supervised home-based exercise of either higher or lower intensity and who were less stressed and less fit at baseline than other individuals had the greatest probability of successful adherence by the 2nd year. Overweight individuals assigned to a group-based exercise program were the least likely to be successful 2 years later. Predictors of short-term (1-year) adherence were generally similar to predictors of 2-year adherence. Signal detection analysis may be useful for identifying subgroups of people at risk for underadherence who subsequently might be targeted for intervention.
miRNAs appear to be potent regulators of gene expression in endometriosis and its associated reproductive disorders, raising the prospect of using miRNAs as biomarkers and therapeutic tools in endometriosis.
In this study, women with dysmenorrhea of at least 6 months' duration were recruited to a randomized, double-blind, controlled trial, which compared the effectiveness of conservative surgical treatment with treatment with presacral neurectomy. One hundred twenty-six women with a diagnosis of dysmenorrhea caused by endometriosis who had been unresponsive to medical treatment formed the study subjects. A preoperative evaluation established a baseline for frequency and severity of dysmenorrhea, dyspareunia, and chronic pelvic pain. Similar measurements were made at 6 and 12 months. Pain severity was rated using a 100-point visual analog scale with 100 being the most severe pain. Patients were randomized to 1 of 2 treatment groups. Group A (n ϭ 63) received electrocautery ablation or excision of visible pelvic endometriotic lesions, enucleation of endometriomas, and lysis of pelvic adhesions. Group B (n ϭ 63) underwent presacral neurectomy after conservative treatment. Presacral neurectomy was performed after retraction of the sigmoid colon and vasopressin infiltration of the sacral promontory area. The presacral area was exposed and underlying tissue layers cauterized. At the periosteum, a semilunar piece of retroperitoneal tissue was dissected. Neurectomy was confirmed with pathologic examination of this tissue for evidence of nerve fiber presence. The 2 treatment groups were similar in demographic and clinical data. All laparoscopies were successfully completed with no surgical complications in either group. The length of surgery was significantly greater for those in group B (mean 123 minutes vs. 110 minutes; P Յ.05), but otherwise all operative parameters were similar. Short-term complications were minimal in both groups. No patient in group A had long-term complications. In group B, 21 and 9 women, at the 6-and 12-month visits, respectively, reported constipation. Medical therapy was successful in 15 of the 21 women at 6 months. Three patients reported urinary urgency at both the 6-and 12-month follow up. At the 6-month and 12-month visits, 83.2% and 85.6%, respectively, of the patients in group B reported either no dysmenorrhea or only light discomfort and were considered cured. In comparison, 60.3% and 57% of the women in group A were cured at 6 and 12 months, respectively (P Յ.05 for both). At each stage of endometriosis, and in women with deep rectovaginal septum endometriosis, the cure rate in group B was significantly higher compared with those in group A. Women in group A who had deep rectovaginal septum endometriosis were less likely to be cured compared with all stages of endometriosis in the same group. The severity of dysmenorrhea and dyspareunia was significantly improved at the 6-and 12-month visit in group B compared with group A, but the frequency of symptoms was similar in both groups after treatment. ABSTRACTTwo hundred nulliparous women were enrolled in a prospective observational study to investigate the influence of childbirth on pelvic organ mobility. The mobility of the urethra, bladder, c...
We could not statistically evaluate most of the biomarkers assessed in this review in a meaningful way. In view of the low quality of most of the included studies, the findings of this review should be interpreted with caution. Although PGP 9.5 met the criteria for a replacement test, it demonstrated considerable inter study heterogeneity in diagnostic estimates, the source of which could not be determined. Several endometrial biomarkers, such as endometrial proteome, 17βHSD2, IL-1R2, caldesmon and other neural markers (VIP, CGRP, SP, NPY and combination of VIP, PGP 9.5 and SP) showed promising evidence of diagnostic accuracy, but there was insufficient or poor quality evidence for any clinical recommendations. Laparoscopy remains the gold standard for the diagnosis of endometriosis, and using any non-invasive tests should only be undertaken in a research setting. We have also identified a number of biomarkers that demonstrated no diagnostic value for endometriosis. We recommend that researchers direct future studies towards biomarkers with high diagnostic potential in good quality diagnostic studies.
There is a compelling case that microRNAs, long non-coding RNAs and short inhibitory RNAs have the potential to influence endometriosis development and persistence through modulating inflammation, proliferation, angiogenesis and tissue remodelling. Rapid advances in ncRNA biomarker discovery and therapeutics relevant to endometriosis are emerging. Unravelling the significance of ncRNAs in endometriosis will pave the way for new diagnostic tests and identify new therapeutic targets and treatment approaches that have the potential to improve clinical options for women with this disabling condition.
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