Therapy For Endometriosis Research Articles

Peritoneal fluid progesterone and progesterone resistance in superficial endometriosis lesions.

Peritoneal fluid in ovulatory women is an ovarian exudate with higher estrogen and progesterone concentrations than in plasma. In the follicular phase, progesterone concentrations are as high as plasma concentrations in the luteal phase. After ovulation, estrogen and progesterone concentrations in the peritoneal fluid are 5-10 times higher than in plasma, both in women with and without endometriosis. The histologically proliferative aspect without secretory changes of most superficial subtle lesions is not compatible with the progesterone concentrations in the peritoneal fluid. Therefore, we have to postulate a strong progesterone resistance in these lesions. The mechanism is unclear and might be a peritoneal fluid effect in women with predisposing defects in the endometrium, or isolated endometrial glands with progesterone resistance, or subtle lesions originating from the basal endometrium: the latter hypothesis is attractive since in basal endometrium progesterone does not induce secretory changes while progesterone withdrawal, not occurring in peritoneal fluid, is required to resume mitotic activity and proliferation. Hormone concentrations in the peritoneal fluid are an important factor in understanding the medical therapy of endometriosis. The effect of oestro-progestin therapy on superficial endometriosis lesions seems to be a consequence of the decreased estrogen concentrations rather than a direct progestin effect. In conclusion, the peritoneal fluid, being a secretion product of the ovarian follicule, deserves more attention in the pathophysiology and treatment of endometriosis.

Nonhormonal therapy for endometriosis based on energy metabolism regulation.

Ovarian function suppression is the current pharmacotherapy of endometriosis with limited benefit and adverse effects. New therapeutic strategies other than hormonal therapy are developed based on the molecular mechanisms involved in the hypoxic and oxidative stress environments and metabolism unique to endometriosis. A literature search was performed between January 2000 and March 2021 in the PubMed database using a combination of specific terms. Endometriosis-associated metabolic changes have been organized into four hallmarks: (1) glucose uptake, (2) aerobic glycolysis, (3) lactate production and accumulation, and (4) metabolic conversion from mitochondrial oxidative phosphorylation (OXPHOS) to aerobic glycolysis. Endometriotic cells favor glycolytic metabolism over mitochondrial OXPHOS to produce essential energy for cell survival. Hypoxia, a common feature of the endometriosis environment, is a key player in this metabolic conversion, which may lead to glucose transporter overexpression, pyruvate dehydrogenase kinase 1 (PDK1) and lactate dehydrogenase kinase A (LDHA) activation, and pyruvate dehydrogenase complex inactivation. Evading mitochondrial OXPHOS mitigates excessive generation of reactive oxygen species (ROS) that may trigger cell death. Therefore, the coinactivation of LDHA and PDK1 can induce the accumulation of mitochondrial ROS by converting energy metabolism to mitochondrial OXPHOS, causing endometriotic cell death. Metabolic pattern reconstruction in endometriotic lesions is a critical factor in cell survival and disease progression. One therapeutic strategy that may avoid hormone manipulation is focused on mitigating metabolic changes that have been detected in cells/tissues from women with endometriosis.Lay summaryThe most commonly used medical therapies for endometriosis have contraceptives and other side effects associated with hormone suppression and are therefore unsuitable for women desiring pregnancy. One therapeutic strategy that may avoid hormone manipulation is focused on changing metabolic profiles that have been detected in cells/tissues from women with endometriosis. Endometriotic cells favor glycolytic metabolism over mitochondrial oxidative phosphorylation (OXPHOS) to produce essential energy for cell growth. Furthermore, the metabolic conversion from mitochondrial OXPHOS to aerobic glycolysis suppresses cell death through the reduced generation of reactive oxygen species (ROS). This unique metabolic feature of endometriosis is important for cell survival and disease progression. Thus, changing the specific metabolic switch may increase mitochondrial ROS production, causing severe oxidative stress and cell death. This review describes new treatments by changing the metabolic profiles of endometriosis.

Pathogenesis Based Diagnosis and Treatment of Endometriosis.

Understanding the pathophysiology of endometriosis is changing our diagnosis and treatment. Endometriosis lesions are clones of specific cells, with variable characteristics as aromatase activity and progesterone resistance. Therefore the GE theory postulates GE incidents to start endometriosis, which thus is different from implanted endometrium. The subsequent growth in the specific environment of the peritoneal cavity is associated with angiogenesis, inflammation, immunologic changes and bleeding in the lesions causing fibrosis. Fibrosis will stop the growth and lesions look burnt out. The pain caused by endometriosis lesions is variable: some lesions are not painful while other lesions cause neuroinflammation at distance up to 28 mm. Diagnosis of endometriosis is made by laparoscopy, following an experience guided clinical decision, based on history, symptoms, clinical exam and imaging. Biochemical markers are not useful. For deep endometriosis, imaging is important before surgery, notwithstanding rather poor predictive values when confidence limits, the prevalence of the disease and the absence of stratification of lesions by size, localization and depth of infiltration, are considered. Surgery of endometriosis is based on recognition and excision. Since the surrounding fibrosis belongs to the body with limited infiltration by endometriosis, a rim of fibrosis can be left without safety margins. For deep endometriosis, this results in a conservative excision eventually with discoid excision or short bowel resections. For cystic ovarian endometriosis superficial destruction, if complete, should be sufficient. Understanding pathophysiology is important for the discussion of early intervention during adolescence. Considering neuroinflammation at distance, the indication to explore large somatic nerves should be reconsidered. Also, medical therapy of endometriosis has to be reconsidered since the variability of lesions results in a variable response, some lesions not requiring estrogens for growth and some being progesterone resistant. If the onset of endometriosis is driven by oxidative stress from retrograde menstruation and the peritoneal microbiome, medical therapy could prevent new lesions and becomes indicated after surgery.

GnRH Antagonists with or without Add-Back Therapy: A New Alternative in the Management of Endometriosis?

To evaluate the effectiveness of a new class of medical drugs, namely oral gonadotropin-releasing hormone (GnRH) antagonists, in the management of premenopausal women with endometriosis-associated pelvic pain. We reviewed the most relevant papers (n = 27) on the efficacy of new medical alternatives (oral GnRH antagonists) as therapy for endometriosis. We first briefly summarized the concept of progesterone resistance and established that oral contraceptives and progestogens work well in two-thirds of women suffering from endometriosis. Since clinical evidence shows that estrogens play a critical role in the pathogenesis of the disease, lowering their levels with oral GnRH antagonists may well prove effective, especially in women who fail to respond to progestogens. There is a need for reliable long-term oral treatment capable of managing endometriosis symptoms, taking into consideration both the main symptoms and phenotype of the disease. Published studies reviewed and discussed here confirm the efficacy of GnRH antagonists. There is a place for GnRH antagonists in the management of symptomatic endometriosis. Novel algorithms that take into account the different phenotypes are proposed.

Cell-Penetrating Peptide and siRNA-Mediated Therapeutic Effects on Endometriosis and Cancer In Vitro Models.

Gene therapy is a powerful tool for the development of new treatment strategies for various conditions, by aiming to transport biologically active nucleic acids into diseased cells. To achieve that goal, we used highly potential delivery vectors, cell-penetrating peptides (CPPs), as oligonucleotide carriers for the development of a therapeutic approach for endometriosis and cancer. Despite marked differences, both of these conditions still exhibit similarities, like excessive, uncoordinated, and autonomous cellular proliferation and invasion, accompanied by overlapping gene expression patterns. Thus, in the current study, we investigated the therapeutic effects of CPP and siRNA nanoparticles using in vitro models of benign endometriosis and malignant glioblastoma. We demonstrated that CPPs PepFect6 and NickFect70 are highly effective in transfecting cell lines, primary cell cultures, and three-dimensional spheroids. CPP nanoparticles are capable of inducing siRNA-specific knockdown of therapeutic genes, ribonucleotide reductase subunit M2 (RRM2), and vascular endothelial growth factor (VEGF), which results in the reduction of in vitro cellular proliferation, invasion, and migration. In addition, we proved that it is possible to achieve synergistic suppression of endometriosis cellular proliferation and invasion by combining gene therapy and hormonal treatment approaches by co-administering CPP/siRNA nanoparticles together with the endometriosis-drug danazol. We suggest a novel target, RRM2, for endometriosis therapy and as a proof-of-concept, we propose a CPP-mediated gene therapy approach for endometriosis and cancer.

Medical Treatment for Endometriosis: Tolerability, Quality of Life and Adherence.

Endometriosis is associated with painful symptoms, infertility, sexological difficulties, and psychological suffering. All these symptoms have a negative impact on the overall quality of life of women with the disease, with significant personal, social and economic costs. Several medical options are available to manage symptomatic endometriosis. The pharmacological treatment for endometriosis-related pain may be necessary for decades, or at least until there is a desire for pregnancy or physiologic menopause occurs. In this perspective, clinicians should consider not only the efficacy, but also side effects, tolerability, and costs, along with women's preferences toward different treatments. In this mini-review, we analyzed the pros and cons of the available drugs for the medical therapy of endometriosis, such as estrogen-progestins, progestins, GnRH agonist and GnRH antagonists.

Effects of dual inhibition of AKT and ERK1/2 pathways on endometrial pro-inflammatory, hormonal, and epigenetic microenvironment in endometriosis

Endometriosis is an estrogen-dependent and progesterone-resistant gynecological inflammatory disease of reproductive-age women. The prevalence of endometriosis is ~5–10% in reproductive-age women, increasing to 20–30% in women with subfertility. The current anti-estrogen therapies can be prescribed only for a short time because of the undesirable side effects on menstruation, pregnancy, bone health, and failure to prevent a recurrence. The causes of endometriosis-associated infertility are multifactorial and poorly understood. The objective of the present study was to determine the inhibitory effects of AKT and/or ERK1/2 pathways on the microenvironment of the endometrium in a xenograft mouse model of endometriosis of human origin. Results indicate that dual inhibition of AKT and ERK1/2 pathways, but not inhibition of either AKT or ERK1/2 pathway, suppresses the growth of the endometriotic lesions in vivo. Dual inhibition of AKT and ERK1/2 pathways suppresses the production of proinflammatory cytokines, decreases E2 biosynthesis and signaling, and restores progesterone receptor-B signaling components in the epithelial and stromal cells of the endometrium in a cell-specific manner. These results together suggest that dual inhibition of AKT and ERK1/2 pathways suppresses the estrogen-dominant state and concomitantly increases the progesterone-responsive state of the endometrium. Therefore, dual inhibition of AKT and ERK1/2 pathways could emerge as long-term nonsteroidal therapy for endometriosis.

P–331 The #Enzian classification: A comprehensive non-invasive and surgical description system for endometriosis

Abstract Study question Is there a classification for a complete mapping of endometriosis, including anatomical location, size of the lesions, and degree of involvement that can be used with both, diagnostics and surgery? Summary answer #Enzian classification improves in both, non-invasive diagnostic methods and surgical therapy for endometriosis as a universally usable classification system for all aspects of the disease. What is known already The most commonly used r-ASRM classification has certain limitations due to its incomplete description of DE, the complexity of the classification, and lack of reproducibility. In contrast, the Enzian classification, which has been implemented in the last decade, has proved to be the most suitable for the description of DE. However, since it does not include peritoneal and ovarian lesions and lacks a description of tubo-ovarian adhesions, it has not gained full acceptance. A combination of classification with different systems such as r-ASRM, EFI score and Enzian, may complicate classification of the disease due to overlaps and time-consuming documentation. Study design, size, duration The result is a consensus of a panel of renowned clinicians (working group), gynaecological surgeons and sonographers with extensive expertise in diagnosis and therapy of endometriosis. A first draft was written in 2019 by a joint effort of the first and last author and sent to all working group members. Taking all comments into account, a revised draft was then sent to all coauthors and repeated until a consensus was reached (9 revisions). Participants/materials, setting, methods Criteria used to invite the experts to participate in this consensus process included their having significant peer-reviewed publications in the field of diagnosis and management of endometriosis. Main results and the role of chance Our current proposal is the first of its kind to universally describe superficial and deep endometriosis, ovarian endometriosis, adenomyosis and adhesions by using a classification system that can be applied by gynaecologists, surgeons, sonographers and radiologists following the same principles. The correlation between preoperative and surgical staging, on the basis of the Enzian scheme, allows for consistent and clear classification of endometriosis, especially DE. Endometriosis can be mapped completely with one single classification system enabling the use of one common language. Limitations, reasons for caution This classification system is anatomically logical and should be easy to use. Further studies are ongoing and are needed to provide proof for the applicability, reproducibility and accuracy of the #Enzian classification for the description of endometriosis. Wider implications of the findings: #Enzian classification now enabled better coverage of various endometriosis localizations. The possibility of using this system preoperatively as well as postoperatively within the framework of diagnostics offers clinicians a significant improvement in the care of patients with such a complex disease. Trial registration number Not applicable

P–312 Clinical applications of platelet-rich plasma in poor endometrium patients with adenomyosis

Abstract Study question Does the intrauterus application of platelet-rich plasma (PRP) allow improving the thickness of endometrium in patients with adenomyosis: comparative characteristics of the PRP-techniques? Summary answer The endometrial thickness in poor-endometrium-patients is increased after subendometrial PRP- injection comparing with the endometrium size after PRP- irrigation of the uterine cavity (P < 0.05). What is known already The endometrium plays an important role in achieving optimal outcomes of assisted reproductive technologies. PRP is a novel method that is used in reproductive medicine to improve the IVF outcome. The mechanisms of PRP have not been completely elucidated, but laboratory studies have shown that the high concentration of growth factors in PRP can potentially speed up the healing process. Recently, the intrauterine PRP-infusion and the subendometrial PRP-injection during the hysteroscopy have been described as a way to promote endometrial growth and receptivity. Study design, size, duration Totally 64 patients with adenomyosis and poor endometrium (≤ 6 mm) were divided into three experimental groups depending on PRP administration: intrauterine PRP-infusion, subendometrial PRP-injection and standard hormonal therapy of adenomyosis without PRP application. The period of study – December 2019 – November 2020. The study’s protocol was approved by the Center’s IRB. Participants/materials, setting, methods Intrauterine PRP-infusion was performed for 23 patients with age 34.2±3.6 y.o. (Group 1). Subendometrial PRP-injection was applied for 16 patients with the middle age 32,6±2,4 y.o. (Group 2). Additional hormonal therapy was carried out for patients from Groups 1, 2. The third control Group 3 consisted of 25 adenomyosis women with the middle age 35.7±4.1 y.o. Only the hormonal therapy was performed for patients of the control group. Main results and the role of chance The procedure of intrauterine PRP-infusion was done using the intrauterine catheter on the 8th and 12th days of the f hormone replacement therapy. Subendometrial PRP-injection was performed during the hysteroscopy on the 8th–10th day of the previous menstrual cycle. The control of the endometrium size was done by ultrasound examination. T-test was used for data analysis. P < 0.05 was considered statistically significant. After subendometrial PRP-injection, the average endometrium thickness was significantly higher comparing with the control (8.7±1.1mm vs. 5.8±0.8mm) (Student t-test t = 2.13, P = 0.04). PRP-infusion also showed significantly strong positive result comparing with the control group (8.3±0.9mm vs. 5.8±0.8mm) (Student t-test t = 2.08, P = 0.043). There is the tendency that subendometrial PRP-has a greater impact on endometrium size comparing with the PRP-infusion. Further investigations should be done. Limitations, reasons for caution Patients with Asherman’s syndrome were excluded from experiment. Wider implications of the findings: It is not clear how the intrauterine administration of PRP may act to affect endometrial thickness. Results from studies on the role of endometrial thickness on implantation and live births are contradictory. There is the urge for well-designed randomized studies to improve our knowledge on PRP in reproductive medicine. Trial registration number -

Targeting sphingosine kinase-1 with the low MW inhibitor SKI-5C suppresses the development of endometriotic lesions in mice.

Limited evidence suggests that the sphingosine-1-phosphate/sphingosine kinase 1 (S1P/SPHK1) signalling pathway is involved in the pathogenesis of endometriosis. Therefore, we analyzed in this study whether the inhibition of SPHK1 and, consequently, decreased levels of S1P affected the vascularization and growth of endometriotic lesions. Endometriotic lesions were surgically induced in the peritoneal cavity and the dorsal skinfold chamber of female BALB/c mice. The animals received a daily dose of the SPHK1 inhibitor SKI-5C or vehicle (control). Analyses involved the determination of lesion growth, cyst formation, microvessel density and cell proliferation within peritoneal endometriotic lesions by means of high-resolution ultrasound imaging, caliper measurement, histology and immunohistochemistry. In the dorsal skinfold chamber model the development of newly formed microvascular networks and their microhemodynamic parameters within endometriotic lesions were investigated by means of intravital fluorescence microscopy. SKI-5C significantly inhibited the development and vascularization of peritoneal endometriotic lesions, as indicated by a reduced growth and cyst formation, a lower microvessel density and a suppressed cell proliferation, when compared to vehicle-treated controls. Endometriotic lesions in dorsal skinfold chambers of SKI-5C-treated animals exhibited a significantly smaller lesion size, lower functional microvessel density, smaller microvessel diameters and a reduced blood perfusion of the newly developing microvascular networks. SPHK1/S1P signalling promotes the establishment and progression of endometriotic lesions. The inhibition of this pathway suppresses the development of endometriotic lesions, suggesting SPHK1 as a potential novel target for future endometriosis therapy.

Nonhormonal therapy for endometriosis: a randomized, placebo-controlled, pilot study of cabergoline versus norethindrone acetate

ObjectiveTo estimate the efficacy and safety of a novel nonhormonal therapeutic agent, cabergoline, compared with that of the standard clinical therapy, norethindrone acetate (NETA), for the treatment of endometriosis-associated pain in young women with endometriosis.DesignRandomized, double-blind, placebo-controlled pilot study.SettingTertiary care center.Patient(s)Women (n = 9) with surgically confirmed endometriosis.Intervention(s)A random, double-blind assignment to either NETA (5 mg/day) + placebo twice weekly or cabergoline (0.5 mg) twice weekly + placebo daily for 6 months.Main Outcome Measure(s)We collected the measures of pelvic pain and laboratory parameters every 3 months.Result(s)We observed a decrease in pain scores and increase in pain relief in women randomized to receive cabergoline, who appeared to show similar or more improvements than women treated with NETA. The serum measures of vascular endothelial growth factor receptor 1 declined over 6 months in those who received cabergoline. Cabergoline was well tolerated, and no serious adverse events occurred.Conclusion(s)Safe, effective adjunct treatments are lacking for patients with endometriosis who do not respond to standard care. Because the growth of endometriosis requires angiogenesis, blood vessel growth is an attractive therapeutic target. This pilot study suggests that cabergoline, a vascular endothelial growth factor pathway inhibitor, is an effective therapeutic option for women with chronic pain due to endometriosis. Building upon this investigation, we will conduct larger, randomized trials of cabergoline, advancing research on the best treatments for endometriosis—particularly disease resistant to hormonal therapies.Clinical Trial Registration Numberclinicaltrials.gov; registration number NCT02542410.

Medical management of endometriosis.

Endometriosis is a benign gynecologic disorder that is defined as functional endometrial tissue outside of the uterine cavity. It is an estrogen-dependent, inflammatory disease that leads to symptoms of pelvic pain, dysmenorrhea, dyspareunia, and infertility, occurring in 6-10% of reproductive aged women. The severity of the disease ranges from asymptomatic to debilitating symptoms that have a major impact on women's lives. It is a chronic, recurrent disease, frequently requiring long term management until menopause and beyond. It is considered a chronic disorder that is managed with surgery, medical treatment, and oftentimes, both. Current medical therapy for endometriosis is considered suppressive of the disease, rather than curative. Fortunately, many patients do experience improvement and control of their symptoms with medical therapy. However, long-term efficacy of the medical treatments is often limited by side effects and the cost of therapy, and symptoms do tend to recur after discontinuation of these medications. This review summarizes our understanding of the pathogenesis of endometriosis and provides more in-depth discussion of specific medical management options used to treat endometriosis, including mechanism of action and side effects. It also provides recommendations on strategy with a forward look to novel endometriosis treatments in the future. The authors emphasized that endometriosis is a chronic disorder requiring long term medical therapy. Early diagnosis of endometriosis is key in preventing severe, debilitating symptoms and progression of disease. By utilizing our current knowledge of the pathophysiology of endometriosis and by correctly implementing currently available medical and surgical therapies we can significantly reduce the physical, psychosocial and financial burden of this chronic, recurrent and indolent disease. Current available medications are suppressive therapies, but the authors are looking forward to future therapies that can effectively cure or at least control endometriosis with minimal side effects. Future research should continue to look for the genetic trigger for endometriosis which can lead us to its underlying pathogenesis and eventually a cure or prevention.

PPARγ Agonists: Emergent Therapy in Endometriosis.

Endometriosis is one of the major gynecological diseases of reproductive-age women. This disease is characterized by the presence of glands and stroma outside the uterine cavity. Several studies have shown the major role of inflammation, angiogenesis, adhesion and invasion, and apoptosis in endometriotic lesions. Nevertheless, the mechanisms underlying endometriotic mechanisms still remain unclear and therapies are not currently efficient. The introduction of new agents can be effective by improving the condition of patients. PPARγ ligands can directly modulate these pathways in endometriosis. However, data in humans remain low. Thus, the purpose of this review is to summarize the potential actions of PPARγ agonists in endometriosis by acting on inflammation, angiogenesis, invasion, adhesion, and apoptosis.

Endometriose en pijn: een overzicht met argumentatie voor een individuele en multidisciplinaire aanpak

Endometriosis and pain: an overview with arguments for an individual and multidisciplinary approach This article provides a narrative overview of endometriosis-related pain. Pain due to endometriosis affects quality of life with an impact on professional, social, family and sexual functioning. Both neuropathic and inflammatory mechanisms are at the root of the pain, which is further modulated via central sensitization in the brain. Chronic pain due to endometriosis is associated with morphological changes in pain-processing areas of the central nervous system. These data reinforce the need to frame endometriosis therapy in a much broader sense than just local surgical removal and (hormonal) suppression. Both the diagnosis and the therapy of endometriosis benefit from a multidisciplinary and dedicated team. The literature on the treatment of endometriosis-related pain is characterized by large gaps, there are only a few prospective randomized or placebo-controlled studies. In addition to surgery, estrogestin combinations, progestogens alone, GnRH agonists and antagonists, aromatase inhibitors, selective estrogen and/or progestogen receptor modulators, NSAIDs (non-steroidal anti-inflammatory drugs), psychotherapy and physiotherapy can be used. Except for acupuncture, there are no good comparative studies on alternative treatments, like for example certain nutritional supplements, cannabis, osteopathy and other alternatives. In view of the interdependence of pain complaints in endometriosis patients and its effects on their social and personal experience and functioning, the approach must be based on a patient-oriented program, adapted to the personal needs and preferences of the patient. A multidisciplinary approach with a policy based on the needs and expectations of the patient can be an added value.

Thromboembolic safety profile of low-dose estradiol (valerate) in combined hormonal preparations: Implications for the development of new hormonal endometriosis and uterine fibroid therapies

Background: Several promising new medications containing low-dose estradiol (E2) in combination with a progestin and an additional component, such as gonadotropin-releasing hormone antagonists, are currently being developed for use in pre-menopausal women. Objective: This pooled analysis was designed to estimate the thromboembolic safety profile of E2 and its ester, estradiol valerate (E2Val), when used in combined hormonal treatments in a pre-menopausal population. Methods: Data regarding users of combined oral contraceptives (COCs) and combined menopausal hormonal therapy (MHT) containing either E2/E2Val or ethinylestradiol (EE) ⩽ 30 µg were retrieved from five large prospective, non-interventional, cohort studies in Europe, US, and Canada with similar study design but differing medication cohorts. Propensity score sub-classification was applied to balance baseline parameters between cohorts and time-to-event analysis of venous thromboembolic events (VTE) was carried out based on the extended Cox model to calculate crude and adjusted hazard ratios (HR). Results: (1) Crude incidence rates of VTE were higher in MHT users compared to pre-menopausal COC users, (2) the VTE risk in menopausal users of E2/E2Val-norethindrone acetate was not higher than that in menopausal users of E2/E2Val-progestin (adjusted HR 0.71; 95% confidence interval, 0.41-1.26) and (3) the VTE risk in pre-menopausal users of E2/E2Val-progestin was similar, or lower, than pre-menopausal users of EE⩽30µg-progestin (adjusted HR 0.49; 95% confidence interval, 0.28–0.84). Conclusion: Our data presents a solid safety assessment of combined hormonal preparations containing E2/E2Val. We conclude that the risk of E2/E2Val-norethindrone acetate in pre-menopausal users is unlikely to be higher than the known risk of COCs containing EE ⩽ 30 µg-progestin.

Popularity of endocrine endometriosis drugs and limited alternatives in the present and foreseeable future: A survey among 1420 affected women

ObjectivesEndocrine drugs represent an important cornerstone of endometriosis therapy. Pharmaceutical alternatives with similar efficacy remain out of sight in the near future. Aim of this study is to investigate attitudes and perceptions concerning endocrine therapies among affected women. Study designAn online survey was distributed via social media in Austria, Germany, and Switzerland. Primary endpoints were satisfaction, attitudes and perceptions towards endocrine endometriosis drugs and secondary outcomes differences regarding demographic variables. ResultsOf 1420 respondents, 63.5 % (n = 901) described their own attitude towards these drugs as rather negative. The most frequently reported unfavorable associations and experiences were sideeffects in general (85.5 %, n = 1181), change in libido (67.5 %, n = 932), hormone cycle disruptions (65.9 %, n = 910), and inefficiency at alleviating symptoms (38.2 %, n = 527). In total, 66.1 % (n = 935) were not satisfied with endocrine drugs for endometriosis. Age ≤ 30 years, living in a large city, and having an academic degree were significantly correlated to a more negative perception of these drugs and greater dissatisfaction with current endocrine endometriosis drugs. ConclusionsAmong women with endometriosis - and particularly among those aged ≤30 years, being large-city residents, or holding an academic degree - there appears to be a relevant degree of rejection and wariness towards endocrine endometriosis drugs. Given the prevalence of endometriosis and the few pharmaceutical alternatives on the horizon, these data point a growing need for further research and development of non-hormonal drugs for the treatment of endometriosis.

EXPERIENCE OF LONG-TERM USE OF DIENOGEST FOR THE TREATMENT OF ADENOMYOSIS

Endometriosis refers to a chronic, often recurrent disease that requires the appointment of a long-term management plan and the patient with the appointment of therapy that effectively affects the clinic of this disease, at the same time having good tolerability, ensuring the patient's adherence to this method of treatment. This dictates the need for careful selection of a drug that meets such requirements. Moreover, studies of drug therapy for endometriosis should also be prolonged. In this case, they allow you to qualitatively assess the effectiveness of a particular type of treatment in the context of routine clinical practice. The main clinical manifestations of endometriosis of the uterine body-adenomyosis are pain syndrome, manifested by various types of pain (dysmenorrhea, dyspareunia, dyschesia, chronic pelvic pain) and the presence of abundant uterine bleeding. The presented clinical case demonstrates the effectiveness of long-term (for 36 months) use of dienogest at a dosage of 2 mg per day (the drug Vizanna) in a continuous mode in the treatment of a patient with adenomyosis. By the 4th month of therapy, the pain syndrome, manifested by dysmenorrhea and dyspareunia, which is the leading clinical manifestation of this pathology in the patient, was completely stopped. The proposed type of therapy has also demonstrated its effectiveness in relation to another clinical manifestation of the disease - heavy uterine bleeding. By the 6th month of therapy, the patient had developed persistent amenorrhea. Good tolerability and the absence of side effects, along with a pronounced clinical effect, led to a high adherence of the patient to this type of drug therapy and allowed her to continue it in the future with dynamic monitoring.

Novel herbs and drugs for endometriosis management: A review on current and futuristic therapies

A disorder with estrogen dependency comprising of inflammatory lesions outside the uterus, causing pain and inflammation in pelvis and affecting women of reproductive age with infertility and post reproductive age is endometriosis. Endometriosis is viewed as public health issue with a major impact on quality of life of women. Medically advanced computational and chemical treatments are available to treat the progression of the disease by diagnostic imaging, clinical examinations, imaging and laparoscopy often leading to immediate surgery. A warrantable rethinking on the diagnosis and management of endometriosis is to be assessed and medical treatments should be considered as first-line option for therapeutic relief for endometriosis by suppressing the systemic estrogen levels providing desirable efficacy and safety, prior to performing endometriosis surgery. The aim of this review is to describe natural products, hormonal and non-hormonal compounds that suppress the progression of endometriosis. Various herbal, conventional and traditional therapies are investigated to treat gynecological disease, endometriosis. The information in this paper include various studies assessing the use of novel treatments in addition to the herbal and hormonal products in the endometriosis therapy. Most of the studies involved were in scrutinizing the pharmacological activity profiles of various sources of drugs in endometriosis treatment, hormonal drugs involved suppression and regulation of various hormones along with various factors like anti-inflammatory, anti-oxidant, anti-proliferative and apoptotic, anti-angiogenic, anti-invasive, immunomodulatory, and estrogen modulating activity. However, novel drugs and medicinal plants are also reviewed here to draw attention to the molecules of drugs that target at multiple points for rational therapeutic treatment of endometriosis.

The safety of echo contrast-enhanced ultrasound in high-intensity focused ultrasound ablation for abdominal wall endometriosis: a retrospective study.

We aimed to investigate the efficacy and safety of echo contrast-enhanced ultrasound (CEUS) during high-intensity focused ultrasound (HIFU) ablation therapy for abdominal wall endometriosis (AWE). A total of 67 patients with AWE were treated with HIFU ablation, and their demographic characteristics were retrospectively analysed. Blood perfusion of the focal lesion was assessed before the operation, during ablation and after the operation with the use of an ultrasound contrast agent, and the effect of the ultrasound contrast agent on treatment was assessed over a 1-year follow-up period. The degree of symptom relief and adverse effects were evaluated after HIFU ablation. Eighty-two lesions were ablated in 67 patients. CEUS showed that all lesions were successfully ablated with HIFU. The shrinkage ratio of the lesions significantly increased over the follow-up period. Intermittent pain disappeared at 1 month after the operation, and the patients' pain scores significantly decreased at the 1-year follow-up. The mean [± standard deviation (SD)] lesion volume was 7.64±8.95 cm3 on B-mode ultrasound. The post-HIFU non-perfused volume was 18.34±24.08 cm3, and the rate of massive changes on greyscale imaging was 96.16%±5.44% at 12 months. During the procedure, the main complications were a prickling sensation and tenderness in the treatment area and/or a transient "hot" sensation on the skin. After the procedure, there was no obvious discomfort except for pain. Two patients developed an approximately 1-cm area of skin that exhibited a waxy appearance. Seven patients had haematuria. No severe complications were observed. Ultrasound contrast agents are effective and safe for evaluating the effect of HIFU ablation on AWE, and this approach provides significant guidance and evaluation benefits for the use of HIFU treatment for AWE without obvious side effects.

Establishing a Comprehensive Framework for Future Explorations: An Endometriosis and Cardiovascular Disease Literature Review

Endometriosis is one of the most prominent gynecological disorders often associated with several cardiovascular repercussions. Although no conclusive mechanism has been found, previous literature indicates potential links between endometriosis and atherosclerosis, a vital indicator of cardiovascular disease (CVD). However, with the majority of previous studies overlooking the impact of critical confounding variables and testing for only certain biomarkers, a strong argument towards a link cannot be made. Existing literature was thoroughly analyzed to identify major confounding variables that were unaccounted for to compile a list of vital biomarkers indicative of CVD in women with endometriosis. The stage and severity of the disease, surgery, hormone therapy, and presence of endometriosis in the control group were found to be major confounding variables that should be statistically accounted for. From previous literature, biomarkers that were shown to be highly indicative of CVD included lipid profile, arterial stiffness measures, as well as additional measures of vascular function and structure. Encapsulating vital confounding variables and biomarkers, a comprehensive framework was established for a longitudinal study design. This paper provides a narrative review of the common weaknesses and limitations of past investigations exploring the link between endometriosis and CVD and suggests methods to overcome these considerations. Although existing literature has significantly contributed to the surface-level understanding of the link between endometriosis and CVD, knowledge gaps persist. As a result, repercussions are experienced by women with endometriosis worldwide. To ensure better healthcare for women with endometriosis, greater CVD intervention and prevention is critical. Through the holistic longitudinal study design proposed, improved treatment plans considering the potential CVD risks that women with endometriosis are at a greater likelihood of developing can be implemented.