Endometriosis-associated Pelvic Pain Research Articles

Vilaprisan for the treatment of symptomatic endometriosis: results from a terminated phase 2b randomized controlled trial

ObjectiveEvaluate efficacy and safety of two doses of vilaprisan versus placebo in participants with symptomatic endometriosis. DesignMulticenter, randomized, double-blind, placebo-controlled, parallel-group phase 2b trial (NCT03573336). The initially planned sample size was 315 patients. Recruitment was paused to assess long-term toxicity findings in rodents; although findings were assessed as likely to be of limited clinical relevance in humans, the study was closed by the sponsor. During the pause, enrolled patients completed 3 or 6 months of treatment per their assigned regimen. ParticipantsPre-menopausal adults with confirmed endometriosis and moderate-to-severe pelvic pain (≥4/10 on a numerical rating scale) were enrolled. Inclusion required protocol adherence, including ≥24 diary entries, and an average pain score of ≥3.5. InterventionParticipants were randomly assigned 1:1:1 to receive vilaprisan 2 mg, vilaprisan 4 mg, or placebo. Main Outcome MeasuresPrimary outcome was change in 7-day mean “worst pain” (per the Endometriosis Symptom Diary item 1) from baseline to Month 3. All analyses were descriptive only. ResultsEight participants were randomly assigned to treatment before the study pause: six received vilaprisan (4 mg, n=4; 2 mg, n=2) and two received placebo. The six vilaprisan recipients experienced an improvement in endometriosis-associated pelvic pain, whereas the two placebo recipients experienced no change or increased pain; all eight participants had decreased use of pain medication. Bleeding intensity decreased from baseline in the vilaprisan group. ConclusionThe study findings suggest that vilaprisan may improve outcomes in patients with endometriosis. Further studies in larger populations would be needed to accurately assess treatment effects.

World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonization Project: V. Physical examination standards in endometriosis research

The World Endometriosis Research Foundation (WERF) established the Endometriosis Phenome and Biobanking Harmonisation Project (EPHect) to create standardized documentation tools (with common data elements) to facilitate the comparison and combination of data across different research sites and studies. In 2014, four data research standards were published: clinician-reported surgical data, patient-reported clinical data, and fluid and tissue biospecimen collection. Our current objective is to create an EPHect standard for the clinician-reported physical examination (EPHect-PE) for research studies. An international consortium involving 26 clinical and academic experts and patient partners from 11 countries representing 25 institutions and organizations. Two virtual workshops, followed by the development of the physical examination standards that underwent multiple rounds of iterations and revisions. N/A MAIN OUTCOME MEASURE(S): N/A RESULT(S): The EPHect physical examination (EPHect-PE) tool provides standardised assessment of physical examination characteristics and pain phenotyping. Data elements involve examination of a) back and pelvic girdle; b) abdomen including allodynia and trigger points; c) vulva including provoked vestibulodynia; d) pelvic floor muscle tone and tenderness; e) tenderness on unidigital pelvic exam; f) presence of pelvic nodularity; g) uterine size and mobility; h) presence of adnexal masses; i) presence of incisional masses; j) speculum examination; k) tenderness and allodynia at an extra-pelvic site (e.g. forearm); and l) recording of anthropometrics. The EPHect physical examination standards (EPHect-PE) will facilitate the standardised documentation of the physical examination, including the assessment and documentation of examination phenotyping of endometriosis-associated pelvic pain.

Evaluation of Efficacy and Safety of 2 mg vs 4 mg Dienogest in Endometriosis: A Randomised Single-blind Dose-ranging Trial

Introduction: Endometriosis is a recurring chronic inflammatory condition that affects females of reproductive age. Endometriosis-associated Pelvic Pain (EAPP) adversely impacts physical, mental, and social well-being. Currently, there is no ideal treatment option. Dienogest, a selective progestin, shows a pronounced effect on endometriosis. Aim: To compare the efficacy and safety of Dienogest at doses of 2 mg and 4 mg/day orally in the treatment of endometriosis. Materials and Methods: An observer-blind, parallel-group, randomised clinical trial was conducted in the Department of Obstetrics and Gynaecology at IPGME&R, SSKM Hospital, Kolkata, West Bengal, India, from April 2016 to December 2017. A total of 190 women aged 20-45 years suffering from endometriosis were recruited and divided into two treatment groups, A and B, receiving daily doses of 2 mg and 4 mg, respectively, for 24 weeks. Relief of EAPP was assessed using the Visual Analogue Scale (VAS) score, and improvement in Quality of Life (QoL) was measured. Treatment-related adverse events were also recorded. Numerical variables were compared using Student’s t-test or the Mann-Whitney U Test, and categorical variables were compared using the Chi-square test or Fisher’sexact test. Results: The absolute reduction in pelvic pain VAS score was 39.71±8.60 at 24 weeks from the initial score of 70.88 (Mean VAS score before treatment with Dienogest) in Group A, compared to 34.80±6.45 from 69.34 (Mean VAS score before treatment with Dienogest) in Group B (p=0.0001). The difference in mean VAS at 24 weeks between the two groups was statistically significant (p=0.0002). At 24 weeks, 18 (24.66%) patients in Group A experienced an irregular bleeding pattern compared to 27 (40.30%) in Group B, with spotting being the most common issue. Adverse effects such as weight gain, acne, alopecia, depression, and decreased libido were observed in both groups, but they were more pronounced in the 4 mg group. Conclusion: The efficacy and safety results from this doseranging study of Dienogest indicate that 2 mg/day is the effective dose for treating endometriosis and offers better tolerability compared to the 4 mg dose.

Resolution of the First Ukrainian endometriosis forum “Drug treatment for endometriosis-associated pelvic pain. The quality of a woman’s life”

Endometriosis affects 10% of all women of reproductive age, i.e. 190 million patients. Ukraine currently does not gather statistics on the incidence of endometriosis, but, at a rough estimate, this number is approximately 280 thousand women and the real number may be higher. Endometriosis has known significant social, medical and economic impact. Therefore, Ukrainian leading specialists in obstetrics and gynecology focus on new treatments for endometriosis, given current scientific data and the needs of patients. The given resolution and algorithms for treatment for endometriosis are the common stand of leading specialists in gynecology in our country and were developed on the basis of modern domestic and foreign data and current clinical guidelines. This resolution aims to improve clinical approaches to the routine practice of treatment for endometriosis. The constant increase in the incidence of endometriosis and its management characteristics allows to conduct an extensive study of the effectiveness and safety profile of various progestogens. In recent years, a number of further evidence have appeared regarding dydrogesterone treatment for endometriosis. New data on the effectiveness of dydrogesterone offer another hormone-based treatment for endometriosis, which is extremely important given the need for long-term and individualized treatment for endometriosis.The Europ ean Society of Human Reproduction and Embryology (ESHRE) states that the degree of pain relief in endometriosis is the same for all hormone-based treatments, but the safety and tolerability profiles of different medicinal products differ, which must be considered. According to the obtained data on the effectiveness and metabolic safety profile of various progestogens and during the discussion, algorithms for dydrogesterone-based treatment for endometriosis were proposed.

Substituting a randomised placebo control group with a historical placebo control in an endometriosis pain trial: a case study re-evaluating trial data using historical control data from another trial

ObjectiveThe substitution of an in-study control population with a historical control (HC) population is considered a viable option for reducing the necessary recruitment of control patients. However, it is necessary...

Quality of life and clinical factors in women with endometriosis, the role of dienogest vs EE/dienogest over time: a single-center study

PurposeThe aims of this observational study were: to assess the relationship between psychological variables, pain, Duration Untreated Endometriosis (DUE) in a sample of women with Endometriosis; and to assess the effect of dienogest 2 mg/daily (DNG) and dienogest/ethinylestradiol 0.03 mg/daily (EE/DNG) on Symptoms, QoL, HRQoL, pain and sexual satisfaction, over time.Methods64 women constituted the study group; (56%) took DNG and (44%) took EE/DNG. VAS, SF-36, EHP-30 and ISS were used to assess endometriosis-associated pelvic pain, QoL, HRQoL and sexual satisfaction, respectively. The study included one follow-up at 18 months.ResultsAt T0, a longer period of DUE was related both to worst HRQoL and Physical QoL. At T1, a correlation was found between longer DUE and worst HRQoL. At T0, a negative correlation was found between VAS and PCS and between VAS and EHP-30. At T1, the same above correlation was found between VAS and PCS/MCS and VAS and EHP-30 scale. There was a correlation between ISS and VAS. ANOVA showed a reduction in dysmenorrhea, in general pain level and an improvement in emotional wellbeing, relationship with medical profession, and PCS over time, regardless to type of treatment. Moreover, a significant time × treatment group interaction for dysmenorrhea was found.ConclusionDUE and pain are important variables related to psychological aspects of women with endometriosis. Treatment with both DNG and EE/DNG may have positive effects on the QoL, HRQoL and symptoms. Moreover, DNG seems to have a greater effect than EE/DNG on dyspareunia reduction over time.

Profile of Linzagolix in the Management of Endometriosis, Including Design, Development and Potential Place in Therapy: A Narrative Review.

Estrogens play a critical role in the pathogenesis of endometriosis and it is logical to assume that lowering estradiol levels with oral gonadotropin-releasing hormone (GnRH) antagonists may prove effective, especially in women who fail to respond to progestogens. Indeed, due to progesterone resistance, oral contraceptives and progestogens work well in two-thirds of women suffering from endometriosis, but are ineffective in 33% of women. Oral GnRH antagonists have therefore been evaluated for management of premenopausal women with endometriosis-associated pelvic pain. The first publication on these drugs reported the efficacy of elagolix. The present paper is a narrative review of linzagolix, which is an orally administered GnRH receptor antagonist with low pharmacokinetic/pharmacodynamic variability. It binds to and blocks the GnRH receptor in the pituitary gland, resulting in a dose-dependent drop in luteinizing hormone (LH) and follicle-stimulating hormone (FSH) production. This reduction in LH and FSH levels in turn leads to a dose-dependent decline in estrogen. Phase 2 and 3 trials are reviewed and discussed here. There is a place for GnRH antagonists in the management of symptomatic endometriosis, and linzagolix with or without add-back therapy (ABT) is one option that can be used at low doses, avoiding the need for ABT, which is contraindicated in some patients.

Clinical Diagnosis and Early Medical Management for Endometriosis: Consensus from Asian Expert Group.

This work provides consensus guidance regarding clinical diagnosis and early medical management of endometriosis within Asia. Clinicians with expertise in endometriosis critically evaluated available evidence on clinical diagnosis and early medical management and their applicability to current clinical practices. Clinical diagnosis should focus on symptom recognition, which can be presumed to be endometriosis without laparoscopic confirmation. Transvaginal sonography can be appropriate for diagnosing pelvic endometriosis in select patients. For early empiric treatment, management of women with clinical presentation suggestive of endometriosis should be individualized and consider presentation and therapeutic need. Medical treatment is recommended to reduce endometriosis-associated pelvic pain for patients with no immediate pregnancy desires. Hormonal treatment can be considered for pelvic pain with a clinical endometriosis diagnosis; progestins are a first-line management option for early medical treatment, with oral progestin-based therapies generally a better option compared with combined oral contraceptives because of their safety profile. Dienogest can be used long-term if needed and a larger evidence base supports dienogest use compared with gonadotropin-releasing hormone agonists (GnRHa) as first-line medical therapy. GnRHa may be considered for first-line therapy in some specific situations or as short-term therapy before dienogest and non-steroidal anti-inflammatory drugs as add-on therapy for endometriosis-associated pelvic pain.

Does Leuprolide Acetate Predict Successful Pain Relief after Hysterectomy and BSO in Endometriosis Patients?

<h3>Study Objective</h3> Evaluate whether patients with endometriosis-associated pelvic pain who achieve pain relief with leuprolide acetate are more likely to achieve pain relief after hysterectomy and oophorectomy (BSO). <h3>Design</h3> Retrospective chart review. <h3>Setting</h3> Academic teaching hospital. <h3>Patients or Participants</h3> Patients who underwent trial of leuprolide acetate prior to hysterectomy and BSO for endometriosis. <h3>Interventions</h3> We performed a retrospective chart review of patients from 2015-2021 who had a diagnosis of endometriosis and underwent a trial of leuprolide acetate prior to hysterectomy with BSO for pelvic pain (n=31). We reviewed pre-operative records, operative notes, and postoperative records to assess whether patients achieved pain relief following ovarian suppression with leuprolide acetate or definitive surgical management with hysterectomy and oophorectomy. Patients who achieved complete pain relief with leuprolide acetate or hysterectomy with oophorectomy were considered having achieved "complete pain relief". <h3>Measurements and Main Results</h3> 31 patients underwent a trial of leuprolide acetate prior to hysterectomy and BSO for endometriosis. Fifteen patients reported "complete pain relief" with leuprolide acetate therapy and 16 did not. The groups were similar in age, ethnicity, race, BMI, parity, number of past treatments for pelvic pain, mode of hysterectomy, blood loss during surgery, presence of adhesions, and surgical complications. There was a significant difference between the two groups as to whether they achieved complete pain relief after hysterectomy with BSO. Among patients with complete pain relief after leuprolide acetate therapy, 73.7% reported complete pain relief after surgery. In patients who did not experience complete pain relief with leuprolide acetate therapy, only 37.5% reported complete pain relief after surgery (p=.045). <h3>Conclusion</h3> Patients who had complete preoperative pain relief using leuprolide acetate were more likely to achieve pain relief with hysterectomy and BSO. A trial of leuprolide acetate prior to surgery may be helpful to predict which patients will benefit from hysterectomy and BSO for endometriosis-related pelvic pain.

Quality of Life in Japanese Patients with Dysmenorrhea or Endometriosis-Associated Pelvic Pain Treated with Extended Regimen Ethinylestradiol/Drospirenone in a Real-World Setting: A Prospective Observational Study.

IntroductionDysmenorrhea and endometriosis are common gynecologic disorders among women of reproductive age that significantly impact health-related quality of life (HRQL) as well as productivity. Although there are treatment options listed in Japanese guidelines, a gap remains in unmet medical needs for maximizing treatment outcome. The extended regimen of ethinylestradiol and drospirenone (EE/DRSP) (taken daily for up to 120 consecutive days) has been available in Japan for treating dysmenorrhea and/or endometriosis-associated pain since 2016. Yet, the effectiveness of its usage on HRQL has not been investigated elsewhere to date. Therefore, in this study, we aim to observe changes in HRQL of Japanese women treated with an extended regimen of EE/DRSP for dysmenorrhea and/or endometriosis-associated pain.MethodsAs part of a 2-year post-marketing surveillance study, women with dysmenorrhea or endometriosis-associated pelvic pain were prescribed extended EE/DRSP during routine clinical practice. Data were collected 1 month before and 3 and 6 months after initiating treatment. Primary outcomes were the Menstrual Distress Questionnaire (MDQ) (before, during, and after menstruation) in patients with dysmenorrhea, and the Endometriosis Impact Scale (EIS) and European Quality of Life 5-dimensions 5-level instrument (EQ-5D-5L) in patients with endometriosis.ResultsThe study cohort included 315 patients (mean age 28.9 years) with dysmenorrhea and 262 patients (mean age 31.3 years) with endometriosis. Mean MDQ total scores before and during menstruation decreased significantly after 6 months with extended EE/DRSP; there was no improvement in after-menstruation MDQ score. Mean EIS domain scores improved significantly by 6 months, with improvement in most EIS individual item scores. Mean EQ-5D-5L scores increased slightly during 6 months of treatment.ConclusionsExtended EE/DRSP treatment improved HRQL outcomes in Japanese women with dysmenorrhea or endometriosis-associated pelvic pain.Trial RegistrationRegistered at ClinicalTrials.gov (NCT03126747) on June 2017.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12325-022-02301-3.

Vitamin D Supplemental Therapy for Women with Endometriosis may ameliorate Endometriosis-associated Pelvic Pain

Vitamin D Supplemental Therapy for Women with Endometriosis may ameliorate Endometriosis-associated Pelvic Pain

Experiences of male partners of women with endometriosis-associated pelvic pain: a qualitative study

Objectives The purpose of the study was to assess the experiences of male partners of women with endometriosis-associated pain after medical treatment in their everyday lives. Methods We conducted a phenomenological study based on semi-structured interviews with 11 male partners of women with endometriosis-associated pelvic pain at the Department of Obstetrics and Gynaecology, University of Campinas Medical School, Brazil. A thematic analysis of manifest content was performed, a coding frame was drafted, and the main analysis categories were elaborated. Results The interviewed men had been in stable relationships for a median length of 14 years. They reported that they did not have information about endometriosis before their partners’ diagnosis and that the endometriosis-associated pelvic pain suffered by their partners affected their personal everyday life, marital relationship, sexual relationship, and intimacy. Conclusion Male partners of women with endometriosis-associated pain reported that the disease has both a profound impact on their lives and on their relationship. Our study contributed to an increased understanding of the life experience of men living with women with endometriosis-associated pelvic pain and may contribute to encourage healthcare professionals to incorporate strategies for guidance of the couple during treatment.

Impact of Long-Term Dienogest Therapy on Quality of Life in Asian Women with Endometriosis: the Prospective Non-Interventional Study ENVISIOeN

Several clinical trials in women with endometriosis demonstrated that dienogest reduces endometrial lesions and improves health-related quality of life (HRQoL). To assess HRQoL in dienogest-treated patients in real-world setting, we conducted a prospective, non-interventional study in 6 Asian countries. Women aged ≥18 years with clinical or surgical diagnosis of endometriosis, presence of endometriosis-associated pelvic pain (EAPP) and initiating dienogest therapy were enrolled. The primary objective was to evaluate HRQoL using the Endometriosis Health Profile-30 (EHP-30) questionnaire. The secondary objectives included analysis of EAPP, satisfaction with dienogest, endometriosis symptoms and bleeding patterns. 887 patients started dienogest therapy. Scores for all EHP-30 scales improved with the largest mean changes at month 6 and 24 in scale pain (−28.9 ± 27.5 and − 34 ± 28.4) and control and powerlessness (−23.7 ± 28.2 and − 28.5 ± 26.2). Mean EAPP score change was −4.6 ± 3.0 for both month 6 and 24 assessments. EAPP decrease was similar in surgically and only clinically diagnosed patients. From baseline to month 24, rates of normal bleeding decreased (from 85.8% to 17.5%) while rates of amenorrhea increased (from 3.5% to 70.8%). Majority of patients and physicians were satisfied with dienogest. Over 80% of patients reported symptoms improvement. 39.9% of patients had drug-related treatment-emergent adverse events, including vaginal hemorrhage (10.4%), metrorrhagia (7.3%) and amenorrhea (6.4%). In conclusion, dienogest improves HRQoL and EAPP in the real-world setting in women with either clinical or surgical diagnosis of endometriosis. Dienogest might be a promising first-line treatment option for the long-term management of debilitating endometriosis-associated symptoms.NCT02425462, 24 April 2015.

Relugolix, an oral gonadotropin-releasing hormone receptor antagonist, reduces endometriosis-associated pain compared with leuprorelin in Japanese women: a phase 3, randomized, double-blind, noninferiority study

To evaluate the efficacy and safety of 40-mg relugolix (REL) compared with those of leuprorelin (LEU) in women with endometriosis-associated pain. Phase 3, multicenter, randomized, double-blind, double-dummy, active-controlled study in Japanese patients. Hospitals and clinics. Women aged ≥20 years with regular menstrual cycles (25-38 days) experiencing endometriosis or ovarian endometrioma and reporting pelvic pain. In the REL group, 40 mg of REL was orally administered once a day for 24 weeks. In the LEU group, 3.75 or 1.88 mg of LEU was subcutaneously injected every 4 weeks for 24 weeks. The primary endpoint was the change in the maximum visual analog scale score for pelvic pain from baseline until 28 days before the end of treatment. Changes in the maximum visual analog scale score were -52.6 ± 1.3 for REL and -57.5 ± 1.4 for LEU. Ovarian endometrioma decreased by 12.26 ± 17.52 cm3 for REL and 14.10 ± 18.81 cm3 for LEU. Drug-related treatment emergent adverse events with an incidence of >10% for both groups were hot flush, metrorrhagia, headache, and genital hemorrhage. Discontinuations from treatment emergent adverse events were 2.9% for REL and 4.3% for LEU. Relugolix was noninferior to LEU for treating endometriosis-associated pelvic pain. Safety profiles of both medications were comparable, although menses returned earlier in patients taking REL, a huge benefit for women who plan to conceive after treatment. ClinicalTrials.gov: NCT03931915.

Efficacy of dienogest vs combined oral contraceptive on pain associated with endometriosis: Randomized clinical trial

ObjectiveTo compare the efficacy of dienogest with the combined oral contraceptive pill (COC) Yasmin for the control of endometriosis-associated pelvic pain. Study designSeventy women with endometriosis-associated chronic pelvic pain, dysmenorrhoea or both for >6 months were randomized to either dienogest (Visanne) 2 mg/day or monophasic COC (Yasmin, 0.03 mg ethinyl estradiol and 3 mg drospirenone) for 24 weeks. The primary efficacy variable was change in non-cyclic pelvic pain and dysmenorrhoea from baseline to end of treatment, assessed using a visual analogue scale (VAS). The secondary efficacy variable was change in the Biberoglu and Behrman (B&B) scale scores for chronic pelvic pain, dysmenorrhoea and dyspareunia. Health-related quality of life (HRQoL) was evaluated using the Endometriosis Health Profile-30 (EHP-30) questionnaire at baseline and 24 weeks. Safety variables included incidence of side-effects, bleeding pattern and treatment tolerability. ResultsBoth treatments improved the mean VAS score for endometriosis-associated pelvic pain significantly: mean difference 6.0 [95% confidence interval (CI) 4.9–7.1; p < 0.0001] in the dienogest group and 4.54 (95% CI 3.1–5.9; p < 0.0001) in the COC group; the difference between them was not significant (p = 0.111). Similarly, both dienogest and COC improved HRQoL in various core and modular segments of the EHP-30 questionnaire with comparable requirements for supplemental pain medication (p = 0.782 and 0.258 at 12 and 24 weeks, respectively), and redistribution of the B&B severity profile for chronic pelvic pain (p = 0.052 and 0.526 at 12 and 24 weeks, respectively), dysmenorrhoea (p = 0.521 and 1 at 12 and 24 weeks, respectively) and dyspareunia (p = 0.376 and 0.835, respectively). Nevertheless, dienogest was associated with fewer side-effects, and hence had a better safety and tolerability profile than COC. ConclusionsDienogest (2 mg/day) is comparable to the COC Yasmin for the relief of endometriosis-associated pelvic pain and improvement in HRQoL.Clinical Trial Registration: Clinicaltrials.gov under number NCT04256200; date of registration 15/1/2020 (registered retrospectively).

Effects of cannabis ingestion on endometriosis-associated pelvic pain and related symptoms.

The use of cannabis for symptoms of endometriosis was investigated utilising retrospective archival data from Strainprint Technologies Ltd., a Canadian data technology company with a mobile phone application that tracks a range of data including dose, mode of administration, chemovar and their effects on various self-reported outcomes, including pelvic pain. A retrospective, electronic record-based cohort study of StrainprintTM users with self-reported endometriosis was conducted. Self-rated cannabis efficacy, defined as a function of initial and final symptom ratings, was investigated across the included symptom clusters of cramps, pelvic pain, gastrointestinal pain, nausea, depression, and low libido. Cannabis dosage form, dose and cannabinoid ratio information was also recorded. A total number of 252 participants identifying as suffering endometriosis recorded 16193 sessions using cannabis between April 2017 and February 2020. The most common method of ingestion was inhalation (n = 10914, 67.4%), with pain as the most common reported symptom being treated by cannabis (n = 9281, 57.3%). Gastrointestinal symptoms, though a less common reason for cannabis usage (15.2%), had the greatest self-reported improvement after use. Inhaled forms had higher efficacy for pain, while oral forms were superior for mood and gastrointestinal symptoms. Dosage varied across ingestion methods, with a median dose of 9 inhalations (IQR 5 to 11) for inhaled dosage forms and 1 mg/mL (IQR 0.5 to 2) for other ingested dosage forms. The ratio of THC to CBD had a statistically significant, yet clinically small, differential effect on efficacy, depending on method of ingestion. Cannabis appears to be effective for pelvic pain, gastrointestinal issues and mood, with effectiveness differing based on method of ingestion. The greater propensity for use of an inhaled dosage delivery may be due to the rapid onset of pain-relieving effects versus the slower onset of oral products. Oral forms appeared to be superior compared to inhaled forms in the less commonly reported mood or gastrointestinal categories. Clinical trials investigating the tolerability and effectiveness of cannabis for endometriosis pain and associated symptoms are urgently required.

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.

The effectiveness of therapy for endometriosis-associated pelvic pain resistant to surgical treatment

Aim. To assess the efficacy and safety of 24-week therapy with dienogest in patients with endometriosis-associated pelvic pain resistant to surgical treatment.&#x0D; Materials and methods. The study included 126 patients aged 3340 years with external genital endometriosis (EGE) confirmed by laparoscopy and morphological examination (International classification of diseases, 10th revision [ICD-10] N80.1, 80.2, 80.3, 80.4) and with pelvic pain that occurred in 36 months after surgical treatment of EGE (ICD-10 N94.8 "Pain and other conditions associated with female genital organs and menstrual cycle"). The participants were stratified into 3 groups by pain syndrome severity according to the Verbal Analog Scale (VAS). The group-1 included patients with 1040 mm, the group-2 with 4170 mm, and the group-3 with more than 71 mm pain score according to VAS. Patients of all 3 groups were prescribed the denogest (Zafrilla, Gedeon Richter, 2 mg/day) for 24 weeks (according to the current pack insert). Follow-up and assessment of treatment outcomes were carried out over 6 months. Study design: prospective, observational, comparative study.&#x0D; Results. In 3 and 6 months after the start of therapy, there was a stable statistically significant decrease in pain syndrome severity by all scales (Biberoglu Behrman Scale, Numeral Rating Scale, VAS) in each of the groups (p0.01). In all 3 groups, treatment led to an improvement in sexual function, assessed with the Female Sexual Function Index scale, in 3 and 6 months after the start of therapy (p0.01). According to the quality of life in endometriosis (Endometriosis Health Profile) questionnaire, the analyzed indicators significantly improved in all study participants (p0.01).&#x0D; Conclusion. Dienogest is an effective and safe method for the treatment of endometriosis-associated pelvic pain resistant to surgical treatment. Treatment with dienogest for 24 weeks effectively relieves pain, improves symptoms, and improves quality of life and sexual functioning.

Bone Mineral Density Changes Associated With Pregnancy, Lactation, and Medical Treatments in Premenopausal Women and Effects Later in Life.

Bone mineral density (BMD) changes during the life span, increasing rapidly during adolescence, plateauing in the third decade of life, and subsequently entering a phase of age-related decline. In women, menopause leads to accelerated bone loss and an increase in fracture risk. Between peak bone mass attainment and menopause, BMD is generally stable and the risk of fracture is typically low. This time period is marked by life events such as pregnancy and lactation, which transiently decrease BMD, yet their long-term effects on fracture risk are less certain. BMD may also be altered by exposure to medications that affect bone metabolism (e.g., contraceptives, glucocorticoids, antidiabetic medications, antiepileptic drugs). Although oral contraceptives are often believed to be neutral with regard to bone health, depot medroxyprogesterone acetate (DMPA) and gonadotropin-releasing hormone (GnRH) agonists have been associated with decreases in BMD. Development of newer medical therapies, principally GnRH antagonists (e.g., ASP1707, elagolix, linzagolix, relugolix), for treatment of endometriosis-associated pelvic pain and heavy menstrual bleeding due to uterine fibroids has renewed interest in the short- and long-term impacts of changes in BMD experienced by premenopausal women. It is important to understand how these drugs influence BMD and put the findings into context with regard to measurement variability and naturally occurring factors that influence bone health. This review summarizes what is known about the effects on bone health pregnancy, lactation, and use of DMPA, GnRH agonists, and GnRH antagonists in premenopausal women and potential consequences later in life. ClinicalTrials.gov identifier: NCT03213457.

Empirical and long-term therapy for endometriosis-associated pelvic pain

Endometriosis is a common disease, the diagnosis and treatment of which is still a matter of debate. One of the main symptoms of endometriosis -pelvic pain is a particular problem due to the difficulties in identifying the cause and the lack of sufficient effect from surgical and medical treatment. The literature review presents current data on the prevalence, clinical characteristics and methods of individualized therapy in patients with pelvic pain established or presumably associated with endometriosis.