Pharmacological and Surgical Approaches to the Management of Endometriosis

Endometriosis is a gynaecological disease characterized by the presence of en - dometrial tissue outside the uterus, causing chronic pain and infertility in many women. The treatment of endometriosis involves pharmacological approaches, such as the use of estroprogestins and GnRH agonists, and surgical interventions to excise the lesions. The choice of treatment depends on the se - verity of the symptoms, the location of the lesions and the patient’s individual response. The management of endometriosis remains a challenge due to resistance to treatment, the variability of the lesions and post-treatment recurrences. This paper reviews the latest tre- atments, highlighting the advances and diffi - culties in managing the disease, with a focus on personalizing therapy to meet the needs of each patient.

Endometriosis, Pharmacological treatment, Surgical excision, Personalized therapy, Pelvic pain, Infertility, Pathophysio - logy.

Endometriosis is a complex gynecological condition that affects a significant proportion of women of reproductive age, with an esti - mated prevalence of between 6% and 10% of the female population. It is characterized by the presence of endometrial tissue outside the uterine cavity, usually in the peritoneum, whi- ch can also affect other organs. The etiology of the disease is not fully understood, but the retrograde menstruation theory is widely ac - cepted, suggesting that endometrial cells flow back into the pelvic cavity during menstrua - tion, settling in ectopic locations. However, in recent years, the genetic-epigenetic (GE) the - ory has gained prominence, proposing that en- dometriosis is triggered by a series of genetic and epigenetic alterations that allow pluripo - tent cells to differentiate into endometrial tis- sue outside the uterus. These alterations partly 3 International Journal of Health Science ISSN 2764-0159 DOI https://doi.org/10.22533/at.ed.1595152518034 explain the variability of the disease, such as the difference in responses to hormonal tre - atments and pain patterns between patients. The evolution of endometriotic lesions is also associated with environmental factors, inclu - ding retrograde menstruation and the perito- neal microbiome, which suggests a complex interaction between genetics, epigenetics and the environment in the development of the di- sease. (AMRO et al., 2022) The symptoms of endometriosis are varied, including chronic pelvic pain, dyspareunia, menorrhagia and, in many cases, infertility. Although laparoscopy is the standard method for diagnosis, imaging tests such as ultrasou - nd and MRI play a key role in the pre-surgical assessment of lesions. Classifying the disease into minimal, mild, moderate and severe sta - ges helps guide treatment, although the severi- ty of the lesions does not always correlate with the intensity of the symptoms. In addition, recent studies highlight that the immune res - ponse plays a crucial role in the viability and growth of endometriotic tissue, with chronic inflammation contributing to prolonged pain and the formation of fibrosis around the le - sions. (PAŠALIĆ; TAMBUW ALA; HROMIĆ- -JAHJEFENDIĆ, 2023) Recognizing these va- riabilities has enabled advances in therapeutic approaches, taking into account the specific characteristics of each patient, such as resis - tance to certain hormones or the presence of remote neuroinflammation, which alters the appropriate treatment. The treatment of endometriosis is multifa- ceted, involving pharmacological and surgi - cal options. Hormonal therapies, such as oral contraceptives, progestogens and GnRH ana- logues, are often used to control the growth of endometrial tissue and relieve symptoms. However, the effectiveness of these therapies can be variable, with some patients showing resistance to the hormones. The surgical approach, on the other hand, focuses on exci- sing the endometriotic lesions, with laparos - copy being the technique of choice. In cases of cystic ovarian endometriosis and deep endo - metriosis, conservative excision is generally preferred, with removal of the lesions without the need for safety margins around the fibrous areas. In addition, superficial removal of cys - tic ovarian lesions is often sufficient to achieve symptom relief. A more detailed understan - ding of the pathophysiology of endometriosis, including the characteristics of the lesions and the associated risk factors, has allowed treat - ment to be personalized, promoting a more effective and less invasive approach. (KONIN- CKX et al., 2021) The search for an early diagnosis, combi - ned with more targeted treatments, represents a significant advance in the management of endometriosis, offering better prospects for disease control and quality of life for affected women. (PAŠALIĆ; TAMBUW ALA; HRO - MIĆ-JAHJEFENDIĆ, 2023) METHODOLOGY The methodology adopted for the litera - ture review aimed to synthesize the latest in - formation on pharmacological and surgical approaches to the management of endome - triosis. To do this, a search was carried out in the PubMed database, using the descriptors ‘Endometriosis’ and ‘Treatment’, in order to select relevant articles published in the last five years. The articles included were those that specifically addressed the treatment of endometriosis, considering both pharmaco - logical and surgical approaches. Studies that were not available in the PubMed database or that did not meet the inclusion criteria, such as those that did not deal directly with the - rapeutic interventions, were excluded. In ad - dition, duplicate articles or those with signi - ficant methodological flaws were disregarded. The selection was carried out carefully, with the aim of ensuring that the studies were cur- 4 International Journal of Health Science ISSN 2764-0159 DOI https://doi.org/10.22533/at.ed.1595152518034 rent, relevant and of high quality, ensuring the reproducibility and transparency of the pro - cess. Based on this analysis, the information extracted was organized in such a way as to provide an up-to-date overview of the diffe - rent treatment options for endometriosis, hi - ghlighting the most recent advances and chal- lenges.

AND DISCUSSION Endometriosis is a multifaceted clinical condition that requires a personalized thera - peutic approach, given the variability of the lesions and the symptoms presented by pa - tients. Pharmacological treatment remains a central option, with the widespread use of es- troprogestins, progestins and GnRH agonists or antagonists, whose therapeutic effects are well documented. However, the effectiveness of these treatments is not uniform, with a sa - tisfactory response in approximately 70% of patients, but minimal or non-existent relief in 10% to 20% of cases. This variability in res - ponse can be attributed to the heterogeneity of endometriotic lesions, which makes it difficult to predict the effectiveness of treatments and requires therapeutic adjustments over time. Periodic evaluation of the treatment using ul- trasound every 6 months has been suggested to monitor the evolution of the lesions, since they can continue to grow even with conti - nued use of the medication. (KONINCKX et al., 2021) In addition, the pathophysiology of endo - metriosis, characterized by high estrogenic activity in the lesions, justifies the medical approach aimed at reducing circulating estro- gen and progesterone levels, particularly in peritoneal lesions, where these hormones are present in significantly higher concentrations than in plasma. However, the effectiveness of this strategy continues to be debated, since some lesions can develop resistance to pro - gesterone and show aromatase activity, which makes treatment more complex. This resis - tance may be related to specific clonal cha - racteristics of the lesions, which show distinct biochemical behaviors, making it difficult to choose a single, effective treatment for all pa - tients. (AMRO et al., 2022; KONINCKX et al., 2021) Surgically, excision of endometriosis le - sions remains the preferred approach in many cases, with the aim of removing as much en - dometriotic tissue as possible with minimal damage to adjacent tissues. Surgical excision is especially recommended for deep lesions and in critical locations, such as the intestine and ureters, where lesions can cause signifi - cant complications, such as intestinal obs - truction and ureteral stenosis. The strategy of conservative excision is discussed, based on the theory that fibrosis can be considered part of the body, which allows for a less inva - sive approach, with short resections and wi - thout the need for wide resections, as occurs in some more aggressive procedures. The use of techniques such as laser vaporization for superficial lesions and chemical destruction, such as alcoholization, for larger lesions, have been suggested as therapeutic options that minimize the risk of recurrence and post-ope- rative adhesions, a frequent problem in more invasive interventions. (AMRO et al., 2022) However, it is important to note that the surgical approach is not without its challen - ges. Recurrences are seen, especially in areas such as the vaginal dome, where wide excision is considered the best strategy to avoid new le- sions. Additionally, the role of neural invasion in pelvic pain associated with endometriosis is still uncertain, and how this affects the sur- gical approach and pain resolution remains a field. (AMRO et al., 2022) 5 International Journal of Health Science ISSN 2764-0159 DOI https://doi.org/10.22533/at.ed.1595152518034

In short, the review carried out shows that the management of endometriosis requires an individualized therapeutic approach, given the complexity and variability of the clinical manifestations of the disease. Pharmacological treatments, which include the use of estroprogestins, progestins and GnRH agonists, have shown significant efficacy in a considerable proportion of patients, although resistance to these hormones and the heterogeneity of the lesions represent major challenges. At the same time, surgical interventions, especially lesion excision, remain essential, especially in cases of deep endometriosis and in critical locations, despite the risk of recurrence and the complications inherent in invasive procedures. Faced with this scenario, personalizing treatment has emerged as a central element for therapeutic success, requiring the integration of clinical, imaging and, where possible, molecular data to guide the choice between pharmacological and surgical approaches. Improved diagnostic methods and continuous research into new therapeutic strategies are essential to optimize the management of the disease, minimizing complications and improving the quality of life of affected women. Therefore, the treatment of endometriosis must be conceived in a dynamic and adaptive way, respecting the particularities of each patient and the challenges inherent in the evolution of the disease.

AMRO, B. et al. New Understanding of Diagnosis, Treatment and Prevention of Endometriosis. International Journal of Environmental Research and Public Health, v. 19, n. 11, p. 6725, 31 maio 2022. KONINCKX, P . R. et al. Pathogenesis Based Diagnosis and Treatment of Endometriosis. Frontiers in Endocrinology, v. 12, p. 745548, 25 nov. 2021. PAŠALIĆ, E.; TAMBUW ALA, M. M.; HROMIĆ-JAHJEFENDIĆ, A. Endometriosis: Classification, pathophysiology, and treatment options. Pathology - Research and Practice, v. 251, p. 154847, nov. 2023.