Endometriosis: Clinical Diagnosis and Treatments

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Obstetrics & Gynecology".

Deadline for manuscript submissions: closed (20 January 2024) | Viewed by 28313

Special Issue Editors


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Guest Editor
Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Ca' Granda Ospedale Maggiore Policlinico, Via Commenda, 12, 20122 Milan, Italy
Interests: endometriosis; adenomyosis; pelvic pain; infertility; homonal treatment; surgery; uterine leiomyoma

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Guest Editor
Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Gynecology Unit, Milan, Italy
Interests: endometriosis; adenomyosis; hormonal treatment; estrogen–progestin; progestin; deep endometriosis; uterine fibroids; hysteroscopy; pelvic pain; surgery

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Guest Editor
1. Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy
2. Gynecological Unit and SVSeD (Service for Sexual and Domestic Violence), Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
Interests: gynecology; endometriosis; sexology; gender violence; domestic violence; sexual violence

Special Issue Information

Dear Colleagues,

In many cases, the diagnosis and treatment of endometriosis represent challenges for clinicians, particularly in cases of deep infiltrating endometriosis or extragenital endometriosis. The risks and diagnostic limitations of surgery and the inaccuracy of clinical examination justify the considerable efforts made to improve the diagnosis with imaging techniques. Additionally, treatment is frequently controversial, despite the availability of several clinical guidelines for endometriosis diagnosis and therapy. The therapeutic approach actually focuses on the management of symptoms related to endometriosis, without specifically addressing the root causes of the disease. Moreover, for infertile patients, medical therapy has a limited role.

Given all the above-mentioned considerations, the aim of this Special Issue is to provide a comprehensive overview of the advances in the diagnosis and treatment of endometriosis. Researchers in the field of endometriosis are encouraged to submit their findings to this Special Issue in the form of original articles or reviews.

Dr. Dhouha Dridi
Dr. Laura Buggio
Dr. Giussy Barbara
Guest Editors

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Keywords

  • endometriosis
  • diagnosis
  • treatment
  • hormonal treatment
  • surgery
  • pain
  • infertility

Published Papers (11 papers)

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Research

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8 pages, 253 KiB  
Article
Outcomes of Urinary Tract Endometriosis—Laparoscopic Treatment: A 10-Year Retrospective Study
by Maria Alexandra Rocha, Gonçalo Mendes, Luis Ferreira Castro, Sofia Mesquita, Bernardo Lobão Teixeira, Mariana Madanelo, João Aragão Vital, Miguel Marques-Monteiro, Nuno Vinagre, Beatriz Oliveira, Martinha Magalhães, Paulo Príncipe, Hélder Ferreira and Miguel Silva-Ramos
J. Clin. Med. 2023, 12(22), 6996; https://doi.org/10.3390/jcm12226996 - 9 Nov 2023
Viewed by 753
Abstract
Introduction: Urinary tract endometriosis (UTE), a rare manifestation, encompasses bladder and ureteral involvement. Surgical intervention is commonly recommended for UTE, though the optimal surgical approach remains a subject of debate. This study aims to report our centre’s experience with UTE. Methods: We conducted [...] Read more.
Introduction: Urinary tract endometriosis (UTE), a rare manifestation, encompasses bladder and ureteral involvement. Surgical intervention is commonly recommended for UTE, though the optimal surgical approach remains a subject of debate. This study aims to report our centre’s experience with UTE. Methods: We conducted a retrospective cohort study of 55 patients who underwent surgical treatment for UTE at a single tertiary centre over a 10-year period (2012–2022). Patient data, including demographics, symptoms, intraoperative findings, and complications, were collected from medical records. Data were statistically analysed, and correlations were explored. Results: The study population had a mean age of 37.11 years, with dysmenorrhea (89.1%) being the most common symptom. Bladder endometriosis was present in 27 cases, ureteral endometriosis in 25, and mixed-location in 3. Laparoscopy was the primary surgical approach, with multidisciplinary teams involving urologists. There were six patients with postoperative complications, and there were six (10.9%) recurrences of endometriosis. A positive correlation was found between age and recurrence, but no significant predictors of recurrence were identified in our analysis. Conclusions: Laparoscopic treatment of urinary endometriosis is safe and effective. Multidisciplinary collaboration plays a pivotal role in addressing this challenging condition. Full article
(This article belongs to the Special Issue Endometriosis: Clinical Diagnosis and Treatments)
17 pages, 2384 KiB  
Article
The Clinical Presentation of Endometriosis and Its Association to Current Surgical Staging
by Matilda Shaked Ashkenazi, Ole Linvåg Huseby, Gard Kroken, Marcela Trocha, Aurora Henriksson, Hanna Jasiak, Karen Cuartas, Alessandra Loschiavo, Isabella Kuhn, Dina Støve, Hanna Grindahl, Emilia Latour, Mathias Melbø, Katrine Holstad and Sebastian Kwiatkowski
J. Clin. Med. 2023, 12(7), 2688; https://doi.org/10.3390/jcm12072688 - 4 Apr 2023
Cited by 2 | Viewed by 2559
Abstract
(1) Despite its high prevalence, the diagnostic delay of endometriosis is still estimated to be about 7 years. The objective of the present study is to understand the symptomatology of endometriosis in patients across various countries and to assess whether the severity of [...] Read more.
(1) Despite its high prevalence, the diagnostic delay of endometriosis is still estimated to be about 7 years. The objective of the present study is to understand the symptomatology of endometriosis in patients across various countries and to assess whether the severity of symptoms correlates with the diagnosed stage of disease. (2) An international online survey collected self-reported responses from 2964 participants from 59 countries. Finalization of the questionnaire and its distribution was achieved by cooperation with various organizations and centers around the globe. (3) Chronic pain presentation remarkably increased between Stage 1 and 2 (16.2% and 32.2%, respectively). The prevalence of pain only around and during menstruation was negatively correlated to the stage, presenting with 15.4% and 6.9% in Stages 1 and 4, respectively. Atypical presentation of pain was most commonly reported in stage 4 (11.4%). Pain related solely to triggering factors was the most uncommon presentation of pain (3.2%). (4) Characteristics of pain and quality of life tend to differ depending on the reported stage of the endometriosis. Further research may allow a better stage estimation and identification of patients with alarming symptomatic presentation indicative of a progressive stage, even those that are not yet laparoscopically diagnosed. Full article
(This article belongs to the Special Issue Endometriosis: Clinical Diagnosis and Treatments)
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9 pages, 714 KiB  
Article
Is There a Correlation between the Second-to-Four Digit Ratio (2D:4D) and Endometriosis? Results of a Case-Control Study
by Laura Buggio, Marco Reschini, Paola Viganò, Dhouha Dridi, Giulia Galati, Alessandra Chinè, Francesca Giola, Edgardo Somigliana and Laura Benaglia
J. Clin. Med. 2023, 12(5), 2040; https://doi.org/10.3390/jcm12052040 - 4 Mar 2023
Viewed by 1728
Abstract
The second-to-four digit ratio (2D:4D) has been proposed as a marker of prenatal hormonal exposure. It is suggested that prenatal exposure to androgens results in a shorter 2D:4D ratio, whereas a prenatal oestrogenic environment results in a longer one. In addition, previous research [...] Read more.
The second-to-four digit ratio (2D:4D) has been proposed as a marker of prenatal hormonal exposure. It is suggested that prenatal exposure to androgens results in a shorter 2D:4D ratio, whereas a prenatal oestrogenic environment results in a longer one. In addition, previous research has shown an association between exposure to endocrine-disrupting chemicals and 2D:4D in animals and humans. On the endometriosis side, hypothetically, a longer 2D:4D ratio, reflecting a lower androgenic intrauterine milieu, could represent an indicator of the presence of the disease. In this light, we have designed a case-control study to compare 2D:4D measurements between women with and without endometriosis. Exclusion criteria included the presence of PCOS and previous trauma on the hand that could impact the measurement of the digit ratio. The 2D:4D ratio of the right hand was measured using a digital calliper. A total of 424 participants (endometriosis n = 212; controls n = 212) were recruited. The group of cases included 114 women with endometriomas and 98 patients with deep infiltrating endometriosis. The 2D:4D ratio was significantly higher in women with endometriosis compared to controls (p = 0.002). There is an association between a higher 2D:4D ratio and the presence of endometriosis. Our results support the hypothesis claiming potential influences of intrauterine hormonal and endocrine disruptors exposure on the onset of the disease. Full article
(This article belongs to the Special Issue Endometriosis: Clinical Diagnosis and Treatments)
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11 pages, 449 KiB  
Article
Systemic Oxidative Stress in Women with Ovarian and Pelvic Endometriosis: Role of Hormonal Therapy
by Anna Biasioli, Anjeza Xholli, Francesca Previtera, Alessandro Balzano, Valentina Capodicasa, Alice Tassi, Ambrogio P. Londero and Angelo Cagnacci
J. Clin. Med. 2022, 11(24), 7460; https://doi.org/10.3390/jcm11247460 - 16 Dec 2022
Cited by 2 | Viewed by 1258
Abstract
This study was performed to evaluate the systemic oxidative stress balance in women with either ovarian or deep infiltrating endometriosis (DIE) and any alterations of the same during hormone therapy. Free oxygen radicals (FORT) and free oxidant radical defense (FORD) were measured in [...] Read more.
This study was performed to evaluate the systemic oxidative stress balance in women with either ovarian or deep infiltrating endometriosis (DIE) and any alterations of the same during hormone therapy. Free oxygen radicals (FORT) and free oxidant radical defense (FORD) were measured in the capillary blood of 24 women without endometriosis, 26 women with endometrioma, and 26 women with DIE with or without endometrioma. Endometriosis was diagnosed by clinical and ultrasound assessment. Dietary factors, lifestyle habits, and intake of any substances interfering with the oxidative status were recorded. Women were prescribed contraceptive hormones, and the baseline assessments were repeated at the 3rd month of use, revealing a higher oxidative stress balance (FORT/FORD) in women with endometriosis than in controls (4.75 ± 4.4 vs. 2.79 ± 2.2; p = 0.05). The highest values were found in women with DIE (5.34 ± 4.6; p = 0.028 vs. controls). Regression analysis revealed an independent link between FORT/FORD and endometrioma (b 2.874, 95% CI 0.345, 5.403; p = 0.027) and DIE (b 4.419, 95% CI 1.775, 7.064; p = 0.001) but a negative correlation with HDL-cholesterol (b −0.063, 95% CI −0.125, −0.002; p = 0.043). In controls, the hormone therapy increased FORT (p = 0.003), but also FORD (p = 0.012), with the FORT/FORD balance remaining stable (2.72 ± 2.2 vs. 2.73 ± 1.8; p = 0.810). In women with endometriosis, FORT remained unchanged, but FORD increased (p = 0.004), and the FORT/FORD ratio significantly decreased (4.75 ± 4.4 vs. 2.57 ± 1.76; p = 0.002) to values similar to the control levels. These data indicate that systemic oxidative stress balance increased in women with endometriosis, particularly in those with DIE. The hormonal therapy did not change the oxidative stress balance in control women but significantly improved it in women with endometriosis, particularly those suffering from DIE. Full article
(This article belongs to the Special Issue Endometriosis: Clinical Diagnosis and Treatments)
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Review

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18 pages, 675 KiB  
Review
The Impact of Conservative Surgical Treatment of Adenomyosis on Fertility and Perinatal Outcomes
by Gaby Moawad, Youssef Youssef, Arrigo Fruscalzo, Hani Faysal, Manuel Merida, Paul Pirtea, Benedetta Guani, Jean Marc Ayoubi and Anis Feki
J. Clin. Med. 2024, 13(9), 2531; https://doi.org/10.3390/jcm13092531 - 25 Apr 2024
Viewed by 688
Abstract
Adenomyosis is a benign condition commonly encountered in patients with infertility. While the definitive surgical management is hysterectomy, conservative surgical management is gaining attention in patients desiring future fertility. This review explores whether the surgical treatment of adenomyosis affects fertility outcomes for patients [...] Read more.
Adenomyosis is a benign condition commonly encountered in patients with infertility. While the definitive surgical management is hysterectomy, conservative surgical management is gaining attention in patients desiring future fertility. This review explores whether the surgical treatment of adenomyosis affects fertility outcomes for patients trying to conceive. The PubMed and Medline databases were searched using the keywords: “adenomyosis”, “surgery”, “radiofrequency”, “infertility”, “pregnancy”, “sterility”, “conception”, “miscarriage”, and “endometrial receptivity”. Abstracts were screened, and relevant articles were selected for review. This review reveals that surgery appears to improve fertility outcomes with or without medical therapy; however, the risk of uterine rupture remains high and the best technique to reduce this risk is still not known. More studies are needed to formulate the best surgical approach for preserving fertility in treating adenomyosis and to establish standardized guidelines. Full article
(This article belongs to the Special Issue Endometriosis: Clinical Diagnosis and Treatments)
16 pages, 528 KiB  
Review
Endometriosis as an Uncommon Cause of Intestinal Obstruction—A Comprehensive Literature Review
by Florentina Mușat, Dan Nicolae Păduraru, Alexandra Bolocan, Alexandru Constantinescu, Daniel Ion and Octavian Andronic
J. Clin. Med. 2023, 12(19), 6376; https://doi.org/10.3390/jcm12196376 - 6 Oct 2023
Viewed by 1354
Abstract
The prevalence of intestinal endometriosis has been estimated to be between 3% and 37% of all endometriosis cases. Cases of intestinal occlusion due to endometriosis foci on the small bowel and on the large bowel are even rarer, with a reported prevalence of [...] Read more.
The prevalence of intestinal endometriosis has been estimated to be between 3% and 37% of all endometriosis cases. Cases of intestinal occlusion due to endometriosis foci on the small bowel and on the large bowel are even rarer, with a reported prevalence of 0.1–0.7%. The aim of this literature review was to summarize the available published evidence on the diagnosis, characteristics, and management of intestinal occlusion due to endometriosis. The search on PubMed retrieved 295 records, of which 158 were rejected following a review of the title and abstract. After reviewing the full text, 97 studies met the Population, Intervention, Comparator, Outcomes, and Study (PICOS) criteria and were included in the analysis. The total number of patients with bowel occlusion due to endometriosis included in the studies was 107. The occlusive endometrial foci were localized on the ileum in 38.3% of the cases, on the rectosigmoid in 34.5% of the cases, at the ileocecal junction and the appendix in 14.9% of the cases, and at the rectum in 10.2% of the cases. Only one case reported large bowel obstruction by endometriosis of the hepatic flexure of the colon extending to the transverse colon (0.9%), and in one case the obstruction was caused by an omental giant endometrioid cyst compressing the intestines. We identified six cases of postmenopausal females with acute bowel obstruction due to endometriosis. Malignant degeneration of endometriosis was also identified as a cause of intestinal occlusion. The mechanisms of obstruction include the presence of a mass in the lumen of the intestine or in the wall of the intestine, extrinsic compression, adhesions, or intussusception. Full article
(This article belongs to the Special Issue Endometriosis: Clinical Diagnosis and Treatments)
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15 pages, 700 KiB  
Review
The Present and the Future of Medical Therapies for Adenomyosis: A Narrative Review
by Gaby Moawad, Youssef Youssef, Arrigo Fruscalzo, Hani Faysal, Mira Kheil, Paul Pirtea, Benedetta Guani, Jean Marc Ayoubi and Anis Feki
J. Clin. Med. 2023, 12(19), 6130; https://doi.org/10.3390/jcm12196130 - 22 Sep 2023
Cited by 3 | Viewed by 2500
Abstract
Uterine Adenomyosis is a benign condition characterized by the presence of endometrium-like epithelial and stromal tissue in the myometrium. Several medical treatments have been proposed, but still, no guidelines directing the management of adenomyosis are available. While a hysterectomy is typically regarded as [...] Read more.
Uterine Adenomyosis is a benign condition characterized by the presence of endometrium-like epithelial and stromal tissue in the myometrium. Several medical treatments have been proposed, but still, no guidelines directing the management of adenomyosis are available. While a hysterectomy is typically regarded as the definitive treatment for adenomyosis, the scarcity of high-quality data leaves patients desiring fertility with limited conservative options. Based on the available data, the levonorgestrel-IUD appears to offer the most favorable outcomes. Other treatments, including GnRH antagonists, dienogest, prolactin, and oxytocin modulators, show promise; however, further data are required to establish their efficacy definitively. Furthermore, there are many emerging therapies that have been developed that seem worthy of consideration in the near future. The aim of this narrative review was to explore the current medical treatments available for adenomyosis and to provide a glimpse of future therapies under assessment. For this scope, we performed a literature search on PubMed and Medline from incept to September 2022 using the keywords: “medical treatment”, “non-steroidal anti-inflammatory”, “progesterone intrauterine device”, “dienogest”, “combined oral contraceptives”, “gonadotropin releasing hormone agonist”, “gonadotropin releasing hormone antagonist”, “danazol”, “aromatase inhibitors”, “ulipristal acetate”, “anti-platelet therapy”, “dopamine”, “oxytocin antagonists”, “STAT3”, “KRAS”, “MAPK”, “micro-RNA”, “mifepristone”, “valproic acid”, “levo-tetrahydropalamatine”, and “andrographolide”. The search was limited to articles in English, with subsequent screening of abstracts. Abstracts were screened to select relevant studies. Full article
(This article belongs to the Special Issue Endometriosis: Clinical Diagnosis and Treatments)
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13 pages, 492 KiB  
Review
Adenomyosis: An Updated Review on Diagnosis and Classification
by Gaby Moawad, Arrigo Fruscalzo, Youssef Youssef, Mira Kheil, Tala Tawil, Jimmy Nehme, Paul Pirtea, Benedetta Guani, Huda Afaneh, Jean Marc Ayoubi and Anis Feki
J. Clin. Med. 2023, 12(14), 4828; https://doi.org/10.3390/jcm12144828 - 21 Jul 2023
Cited by 6 | Viewed by 4806
Abstract
Adenomyosis is a commonly diagnosed benign condition characterized by the presence of ectopic endometrial glands within the underlying myometrium. The most common presenting signs and symptoms are abnormal uterine bleeding, chronic pelvic pain, and infertility. The clinical relevance of this condition is evident [...] Read more.
Adenomyosis is a commonly diagnosed benign condition characterized by the presence of ectopic endometrial glands within the underlying myometrium. The most common presenting signs and symptoms are abnormal uterine bleeding, chronic pelvic pain, and infertility. The clinical relevance of this condition is evident in both medical and surgical care. Histopathology and imaging studies are used for the diagnosis and classification of adenomyosis, which are hallmarks of the advancement of our ability to diagnose adenomyosis. Importantly, the diagnosis and classification of adenomyosis lacks standardization due to the nature of imaging techniques, features of adenomyosis, and the clinical spectrum of adenomyosis. We reviewed the literature to summarize the available classification systems for adenomyosis and highlight the different imaging approaches and histologic criteria used in diagnosis. Despite the high prevalence of the disease, there is no clear consensus on one classification system. We provide a review of some of the classification systems available and discuss their strengths and limitations. Full article
(This article belongs to the Special Issue Endometriosis: Clinical Diagnosis and Treatments)
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18 pages, 704 KiB  
Review
Gonadotropin-Releasing Hormone Antagonists—A New Hope in Endometriosis Treatment?
by Anna Maria Rzewuska, Monika Żybowska, Ilona Sajkiewicz, Izabela Spiechowicz, Klaudia Żak, Monika Abramiuk, Krzysztof Kułak and Rafał Tarkowski
J. Clin. Med. 2023, 12(3), 1008; https://doi.org/10.3390/jcm12031008 - 28 Jan 2023
Cited by 4 | Viewed by 8950
Abstract
Endometriosis is a chronic disease, in which endometrial-like tissue is found outside the uterine cavity. Lesions are typically located in the true pelvis but can be found, in addition to extragenital endometriosis, in the respiratory system, the diaphragm, the pleura or the pericardium. [...] Read more.
Endometriosis is a chronic disease, in which endometrial-like tissue is found outside the uterine cavity. Lesions are typically located in the true pelvis but can be found, in addition to extragenital endometriosis, in the respiratory system, the diaphragm, the pleura or the pericardium. As the extrauterine endometrial lesions undergo the menstrual cycle, they cause many symptoms, including pain, and besides infertility, they all mostly affect the quality of the patient’s life. Pharmacological management of endometriosis significantly increases in importance either as a first-line treatment or as a complementary therapy after surgery. Yet, current research on antagonists of the gonadotropin-releasing hormone (GnRH) has revealed their potential benefits in endometriosis treatment. Their mechanism of action is to down-regulate the hypothalamic–pituitary–gonadal axis and therefore induce a hypoestrogenic state. The resulting reduction of estrogen levels prevents disease progression and diminishes the recurrence rate after surgical removal of endometriosis. The present review summarizes recent reports of the role oral GnRH antagonists have as a significant treatment option for pain reduction in endometriosis patients. Full article
(This article belongs to the Special Issue Endometriosis: Clinical Diagnosis and Treatments)
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Other

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12 pages, 1687 KiB  
Case Report
Chronic Pelvic Puzzle: Navigating Deep Endometriosis with Renal Complications
by Ileana Adela Vacaroiu, Andra-Elena Balcangiu-Stroescu, Iulia-Ioana Stanescu-Spinu, Daniela Gabriela Balan, Mihai-Teodor Georgescu, Maria Greabu, Daniela Miricescu, Elena Cuiban, Larisa Florina Șerban-Feier, Mircea Ovidiu Denis Lupușoru, Alexandra Gaube and Dragos-Eugen Georgescu
J. Clin. Med. 2024, 13(1), 220; https://doi.org/10.3390/jcm13010220 - 30 Dec 2023
Viewed by 945
Abstract
This case report delves into the intricacies of a challenging clinical scenario involving deep pelvic endometriosis, which manifested with renal complications. Endometriosis, a complex gynecological condition, is explored in this case, highlighting its multifaceted nature. The patient presented with a complex interplay of [...] Read more.
This case report delves into the intricacies of a challenging clinical scenario involving deep pelvic endometriosis, which manifested with renal complications. Endometriosis, a complex gynecological condition, is explored in this case, highlighting its multifaceted nature. The patient presented with a complex interplay of symptoms, including chronic pelvic pain, urinary tract issues, and severe deep adenomyosis. The diagnostic journey was protracted, emphasizing the need for early recognition and intervention in such cases. A thorough evaluation, including laparoscopic examination and histopathological analysis, revealed the extensive presence of endometriotic lesions in various pelvic and renal structures, ultimately leading to left hydronephrosis. The report underscores the significance of timely diagnosis and surgical intervention to prevent irreversible renal damage. This case provides valuable insights into the management of deep endometriosis with renal involvement and the importance of interdisciplinary collaboration. Understanding the complexities of this condition can aid in improving patient outcomes and enhancing the quality of care provided. Full article
(This article belongs to the Special Issue Endometriosis: Clinical Diagnosis and Treatments)
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10 pages, 645 KiB  
Systematic Review
Radiofrequency Ablation for Adenomyosis
by Ioannis Dedes, Georgios Kolovos, Fruscalzo Arrigo, David Toub, Cloé Vaineau, Susanne Lanz, Sara Imboden, Anis Feki and Michael D. Mueller
J. Clin. Med. 2023, 12(9), 3069; https://doi.org/10.3390/jcm12093069 - 23 Apr 2023
Cited by 7 | Viewed by 2004
Abstract
Adenomyosis is a common benign gynecologic condition characterized by ectopic endometrial glands and stroma in the myometrium causing pain (dysmenorrhea) and abnormal uterine bleeding. New interventional techniques have been introduced over recent years. This study evaluates the treatment success and side effects of [...] Read more.
Adenomyosis is a common benign gynecologic condition characterized by ectopic endometrial glands and stroma in the myometrium causing pain (dysmenorrhea) and abnormal uterine bleeding. New interventional techniques have been introduced over recent years. This study evaluates the treatment success and side effects of radiofrequency ablation. An electronic literature search in the PubMed, Scopus, and ScienceDirect databases was carried out on the outcomes of pain reduction and, secondarily, on abnormal uterine bleeding, reintervention, reproductive outcome, imaging outcome, and complications. There was a mean decrease in dysmenorrhea pain scores by −63.4 ± 9.0% at 12 months. Data on other outcome parameters were sparse. No major complications were reported. Radiofrequency ablation represents a promising minimally invasive and organ-preserving treatment in patients with symptomatic adenomyosis. It is associated with clinically meaningful improvement of adenomyosis-related pain in the short term. Full article
(This article belongs to the Special Issue Endometriosis: Clinical Diagnosis and Treatments)
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