Effects of dignity therapy on psychological distress and wellbeing of palliative care patients and family caregivers - a randomized controlled study.

BACKGROUND: This study extended the original Dignity Therapy (DT) intervention by including partners and family caregivers (FCs) of terminally-ill cancer patients with the overall aim of evaluating whether DT can mitigate distress in both patients nearing the end of life and their FCs. METHODS: In this multicenter, randomized controlled trial (RCT), a total of 68 patients with life expectancy < 6 months and clinically-relevant stress levels (Hospital Anxiety Depression total score; HADStot ≥ 8) including their FCs were randomly assigned to DT, DT + (including their FCs), or standard palliative care (SPC) in a 1:1:1 ratio. Study participants were asked to complete a set of questionnaires pre- and post-intervention. RESULTS: The coalesced group (DT and DT +) revealed a significant increase in patients' perceived quality of life (FACIT-Pal-14) following the intervention (mean difference 6.15, SD = 1.86, p < 0.01). We found a statistically significant group-by-time interaction effect: while the HADStot of patients in the intervention group remained stable over the pre-post period, the control group's HADStot increased (F = 4.33, df = 1, 82.9; p < 0.05), indicating a protective effect of DT. Most patients and their FCs found DT useful and would recommend it to other individuals in their situation. CONCLUSIONS: The DT intervention has been well-received and shows the potential to increase HRQoL and prevent further mental health deterioration, illness burden and suffering in terminally-ill patients. The DT intervention holds the potential to serve as a valuable tool for facilitating end-of-life conversations among terminally-ill patients and their FCs. However, the implementation of DT within the framework of a RCT in a palliative care setting poses significant challenges. We suggest a slightly modified and less resource-intensive version of DT that is to provide the DT inventory to FCs of terminally-ill patients, empowering them to ask the questions that matter most to them over their loved one's final days. TRIAL REGISTRATION: This study was registered with Clinical Trial Registry (ClinicalTrials.gov -Protocol Record NCT02646527; date of registration: 04/01/2016). The CONSORT 2010 guidelines were used for properly reporting how the randomized trial was conducted.

Systematic, noninvasive endometriosis diagnosis in transvaginal sonography by the Swiss Society of Ultrasound in Medicine.

We present a new systematic, comprehensive, checklist-based sonographic assessment of endometriosis in the female true pelvis. Emphasis is placed on practical skills teaching. The newly introduced White Sliding Line (WSL) is the core structure. The WSL separates five compartments (anterior, central, posterior, and lateral right and left) containing dedicated endometriosis signs of mobility and morphology to be checked. This approach relies on the 2016 IDEA Consensus and further developments. It directly connects to the 2021 #ENZIAN Classification Standard. In practice, evaluation follows the proposed checklist in all compartments, judging first sliding mobility between organs and structures in a highly dynamic investigation. A rigorous search for deep endometriosis (DE) is then performed. We treat adhesions due to their great clinical importance and possible, reliable diagnosis by TVS as the fifth endometriosis unit, next to endometrioma, DE, adenomyosis, and superficial endometriosis. Including superficial (peritoneal) endometriosis is a future goal.

The Predictive Value of Decisive and Soft Ultrasound Criteria for Ectopic Pregnancy Identification in 321 Preoperative Cases.

PURPOSE: To define the predictive value of morphological types (MTs) and further criteria in diagnosing ectopic pregnancy (ECP) by transvaginal sonography (TVS) prior to operative confirmation and treatment. MATERIALS AND METHODS: Retrospective cohort analysis of 321 consecutive patients with suspected ECP who were advised to undergo operation. RESULTS: ECP was investigated by TVS in all 321 patients. Application of the five selected MTs (blob sign, bagel sign, yolk sac, embryo, heart action) resulted in 85 % of cases receiving a conclusive diagnosis and 12 % receiving a presumed ECP diagnosis. 3 % remained nondiagnostic due to large or multiple ovarian cysts, large myoma, extended hemoperitoneum, or severe pain. ECP diagnosis was confirmed intraoperatively in 97 % of cases and was otherwise (3 %) immediately followed by curettage (CUR). The assessment of free fluid by TVS was achieved in most cases and correlated significantly with free blood. In the majority of cases, free blood was not bound to transmural ECP rupture. Histology confirmed the ECP diagnosis directly or by exclusion in 99 % of cases. Three cases of tubal ECP were diagnosed by TVS but not confirmed by LSC (1 %) and, finally, histology from CUR proved miscarriage (false-positive rate 1 %). CONCLUSION: We confirm the high accuracy of TVS diagnosis of ECP relying on five clearly different MTs, independent of its location. The blob and bagel sign emerged as important types (75 % of all ECPs). Histology from CUR was needed when ECP could not be visualized in LSC. Assessment of free fluid was essential and accurate in predicting free blood.

Judging Urgency in 343 Ectopic Pregnancies Prior to Surgery - The Importance of Transvaginal Sonographic Diagnosis of Intraabdominal Free Blood.

OBJECTIVES: Assessing urgency in ectopic pregnancies (ECP) remains controversial since the disorder covers a large clinical spectrum. Severe conditions such as acute abdomen or hemodynamic instability are mostly related to intra-abdominal blood loss diagnosed as free fluid (FF) on transvaginal sonography (TVS). The aims of the current study were to investigate the value of FF and to assess other potentially predictive parameters for judging urgency. METHODS: Retrospective cohort analysis on prospectively collected cases of proven ECP (n = 343). Demographics, clinical and laboratory parameters, and findings on TVS and laparoscopy (LSC) were extracted from the digital patient file. FF on TVS and free blood (FB) in LSC were evaluated. Low urgency was defined as FB (LSC) < 100 ml and high urgency as FB (LSC) ≥ 300 ml. The best subset of variables for the prediction of FB was selected and predictors of urgency were evaluated using receiver operator characteristic (ROC) curves. RESULTS: Clinical symptoms, age, ß-HCG, hemoglobin (HB) preoperative, and FF were examined in multivariate analysis for the cutoff values of 100 ml and 300 ml. FF was the only independent predictor for low and high urgency; HB preoperative was only significant for high urgency offering marginal improvement. ROC analysis revealed FF as an excellent discriminatory parameter for defining low (AUC 0.837, 95% CI 0.794-0.879) and high urgency (AUC 0.902, 95 % CI 0.860-0.945). CONCLUSION: Single assessment of FF on TVS is most valuable for judging urgency. However, the exact cutoff values for a low- and high-risk situation must still be defined.

Endometriosis features and dienogest tolerability in women with depression: a case-control study.

OBJECTIVE: Primary aim of this study was to investigate endometriosis characteristics of patients with psychiatric conditions or depression. The secondary aim was to study tolerability of dienogest in this context. METHODS: This observational case-control study included endometriosis data from patients visiting our clinic from 2015-2021. We collected information from patient charts and in phone interviews based on a structured survey. Patients with surgical confirmed endometriosis were included. RESULTS: 344 patients fulfilled the inclusion criteria: n = 255 no psychiatric disorder, n = 119 any psychiatric disorder and n = 70 depression. Patients with depression (EM-D, p=.018; p=.035) or psychiatric condition (EM-P, p=.020; p=.048) suffered more often from dyspareunia and dyschezia. EM-P patients had more often primary dysmenorrhoea with higher pain scores (p=.045). rASRM stage or localisation of lesions did not differ. EM-D and EM-P patients discontinued dienogest treatment more often related to worsening of mood (p= .001, p=.002). CONCLUSION: EM-D or EM-P had a higher prevalence of pain symptoms. This could not be attributed to differences in rASRM stage or location of endometriosis lesions. Strong primary dysmenorrhoea might predispose to develop chronic pain-based psychological symptoms. Therefore, early diagnosis and treatment are relevant. Gynaecologist should be aware of the potential impact of dienogest on mood.

Women with endometriosis and psychiatric disorders especially have more dyschezia and dyspareunia, independent from rASRM stage, depth of infiltration and localisation of endometriosis lesions. Dienogest has an impact on mood especially in already prone patients.Trial registration: trial registration number: NCT04816357. https://clinicaltrials.gov/ct2/show/NCT04816357Date of registration: 22.03.2021, date of enrolment of the first subject: 25.03.2021.

Effects of vitamin D supplementation in endometriosis: a systematic review.

BACKGROUND: There is a growing body of human, animal and in vitro studies on vitamin D (vit D) substitution in endometriosis. The aim of this systematic review is to critically appraise and qualitatively synthesize the results of the available studies that examine the supplementation of vit D for endometriosis treatment. METHODS: A systematic search of the literature was conducted in four electronic databases (Medline, Cochrane, Scopus, Embase) and grey literature for original research articles on humans, animals and in vitro models published in any language. RESULTS: Four human studies, four animal studies and four in vitro studies were included. Quantitative synthesis of human studies showed no significant effect of vit D intake for dysmenorrhea (2 studies, 44 vit D vs 44 placebo, mean -0.71, 95% CI -1.94, 0.51) and non-cyclic pelvic pain (2 studies, 42 vit D vs 38 placebo, mean 0.34, 95% CI -0.02, 0.71). Regarding reproductive outcomes in women with endometriosis after in vitro fertilization, the only available study showed no differences between women taking vit D and women taking placebo. Three of the four included animal studies showed regression of endometriotic implants when treated with vit D. The in vitro studies demonstrated that vit D decreases invasion and proliferation of endometriotic lesions without affecting apoptosis. CONCLUSIONS: Although in vitro and animal studies suggest regression of the endometriotic implants and decrease of invasion and proliferation after vit D supplementation, this was not reflected in the results of the meta-analysis, which showed no benefit of vit D supplementation in patients with endometriosis and dysmenorrhea or non-cyclic pelvic pain as well as on the outcome of IVF treatment. However, given the heterogeneity and the diversity of the available studies, more research is required to shed light on the role of vit D supplementation in women with endometriosis.

Structured manual for MRI assessment of deep infiltrating endometriosis using the ENZIAN classification.

PURPOSE: Proposal of a systematic approach to assess Deep infiltrating endometriosis (DIE) through pelvic Magnetic resonance imaging (MRI) using the Enzian classification and examination of inter-rater agreement. METHODS: Three radiologists reviewed 23 MRI of patients with pelvic DIE at one tertiary referral center retrospectively and independently. Inclusion criteria were intraoperative confirmation of DIE and MR imaging according to ESUR (European Society of Urogenital Radiology) guidelines. Assessment of the anatomical pelvic compartments was performed using a manual based on the Enzian classification with step-by-step instructions using recommended planes and sequences presented here. Interrater agreement was measured using kappa statistics. RESULTS: According to the intraoperative site lesions in 53 anatomical compartments were present. Interrater agreement was best for compartments A (0.255) and FB (0.642). For FI (0.204) and B (0.146) it was slight, there was poor agreement for C (- 0.263), FA (- 0.022), and FO (- 0.030), respectively, and as for FU, no ureter infiltration was described. CONCLUSION: MRI as a noninvasive diagnostic tool offers essential advantages regarding classification and therapy planning for patients with DIE. However, its assessment is difficult and a more systematic approach is needed. Our proposed manual based on the Enzian classification is reproducible and could support radiologists and gynecologists.

Qualitative and quantitative aspects of sex life in the context of endometriosis: a multicentre case control study.

RESEARCH QUESTION: What are the specific characteristics of sexual activity in women with endometriosis compared with women without endometriosis? DESIGN: Multicentre case control study. Participants were recruited from university hospitals, district hospitals and doctor's offices in Germany, Switzerland and Austria. A total of 565 women with endometriosis were pair-matched to 565 control women by age and ethnic background. Diagnosis of endometriosis was confirmed by histology, and disease stage was classified according to American Society for Reproductive Medicine criteria. Data on sexuality were collected using selected questions from the Brief Index of Sexual Function and the Sexual History Form. RESULTS: Altogether, 69.1% of women with endometriosis and 77.8% of control women engaged in sexual activity during the month before the study period (P < 0.001). Overall, 42.3% of endometriosis-affected women and 30.5% of the control women desired a higher frequency of sexual activity (P < 0.001). Petting, foreplay and vaginal sexual intercourse were reported to be practised less often by women with endometriosis. Frequencies for masturbation, reciprocal masturbation, oral and anal sex were similar in both groups. Dyspareunia was negatively associated with sexual activity (OR 2.42, 95% CI 1.26 to 4.63), whereas chronic pain showed no association with sexual activity (OR 1.35, 95% CI 0.93, 1.96). CONCLUSIONS: Women with endometriosis have lower frequencies of petting, foreplay and vaginal sexual intercourse than control women; this difference has to be attributed, at least in part, to dyspareunia. Potentially pain-free sexual options are used to a limited degree. As endometriosis-affected women desire higher levels of sexual activity, sexual counselling should be included in medical support.

Sexual Satisfaction and Frequency of Orgasm in Women With Chronic Pelvic Pain due to Endometriosis.

BACKGROUND: Dyspareunia, one of the main symptoms of the chronic gynecological pelvic pain disorder endometriosis, may interfere with the likelihood of reaching an orgasm, yet for women with dyspareunia, no data on orgasm rates in different sexual activities are available. AIM: The aim of this study was to evaluate the ability to reach an orgasm and its association with sexual satisfaction during different sexual activities in women with a chronic pelvic pain disorder and in healthy control women. METHODS: A set of questionnaires including the brief index of sexual functioning and global sexual functioning was used to evaluate sexuality in women affected with endometriosis (n = 434) and a nonaffected control group (n = 434) recruited in German-speaking countries. OUTCOMES: The primary outcome measure of this study was the orgasm rate during different types of sexual activities. RESULTS: Only the ability to have an orgasm during sexual intercourse (P = .002) but not during masturbation (P = .509) or partnered noncoital sexual activities (P = .229) is affected by endometriosis. Dyspareunia was associated with a reduced ability to experience an orgasm during intercourse for endometriosis patients (P = .020) and control women (P = .006). The ability to orgasm during noncoital sexual activities (P = .006) and sexual intercourse (P = .038) was associated with a higher sexual satisfaction in women with endometriosis. For controls, only the ability to achieve an orgasm with sexual intercourse was associated with sexual satisfaction (P = .038). CLINICAL IMPLICATIONS: Sexual counselling as part of medical support could help couples living with chronic pelvic pain of the female partner integrate noncoital sexual activities in their sex lives, leading to fewer sex-related problems and higher sexual desire and satisfaction. STRENGTHS AND LIMITATIONS: This study is the first to examine different ways of achieving an orgasm and sexual satisfaction in a large group of women with endometriosis and a matched control group. The breadth of the questionnaire allowed a differentiated analysis of factors influencing the likelihood of achieving an orgasm and overall sexual satisfaction. The one limitation is that the length and the intimate nature of the questionnaire possibly resulted in reluctance to answer this part of the questionnaire. CONCLUSION: Partnered noncoital sexual activities may represent an alternative to reach orgasm for women with endometriosis-related chronic pelvic pain or anorgasmia during sexual intercourse. Hämmerli S, Kohl-Schwartz A, Imesch P, et al. Sexual Satisfaction and Frequency of Orgasm in Women With Chronic Pelvic Pain due to Endometriosis. J Sex Med 2020;17:2417-2426.

Ibrutinib in Gynecological Malignancies and Breast Cancer: A Systematic Review.

Ibrutinib is an orally available, small-molecule tyrosine kinase inhibitor. Its main purpose is to inhibit Bruton's tyrosine kinase (BTK), an enzyme that is crucial in B cell development. It is FDA approved for the treatment of certain hematological malignancies. Several promising off-target drug effects have led to multiple, mostly preclinical investigations regarding its use in solid tumors. Unfortunately, data on its effectiveness in gynecological malignancies are limited, and (systematic) reviews are missing. The objective of this review was to summarize the existing literature and to analyze the evidence of ibrutinib as a treatment option in gynecological malignancies, including breast cancer. Studies were identified in MEDLINE and EMBASE using a defined search strategy, and preclinical or clinical research projects investigating ibrutinib in connection with these malignancies were considered eligible for inclusion. Our findings showed that preclinical studies generally confirm ibrutinib's efficacy in cell lines and animal models of ovarian, breast, and endometrial cancer. Ibrutinib exerts multiple antineoplastic effects, such as on-target BTK inhibition, off-target kinase inhibition, and immunomodulation by interference with myeloid-derived suppressor cells (MDSCs), programmed death-ligand 1 (PD-L1), and T cell response. These mechanisms were elaborated and discussed in the context of the evidence available. Further research is needed in order to transfer the preclinical results to a broader clinical appliance.

Doxycycline reduces MMP-2 activity and inhibits invasion of 12Z epithelial endometriotic cells as well as MMP-2 and -9 activity in primary endometriotic stromal cells in vitro.

BACKGROUND: Matrix metalloproteinases (MMPs), especially the gelatinases MMP-2 and MMP-9, play a crucial role in the pathogenesis of endometriosis by enabling invasion. Doxycycline is a well-tolerated antibiotic and a potent MMP-inhibitor in subantimicrobial doses. METHODS: Gelatin zymography and activity assays were used to detect latent and active MMP-2 and -9 in cell culture supernatants of immortalized epithelial (12Z) and two isolates of primary endometriotic stromal cells treated with doxycycline. The invasiveness of 12Z endometriotic cells treated with doxycycline was assessed in matrigel-coated invasion chambers. The effect on latent and active MMP-2 expression of the combination of progesterone and doxycycline was tested in 12Z. RESULTS: Doxycycline significantly reduced the MMP-2 activity and pro-MMP-2 expression in 12Z and the MMP-2 and -9 activity as well as expression of pro-MMP-2 and -9 in primary endometriotic stromal cells. The percentage of 12Z cells invading through a matrigel-coated membrane was reduced to 65 and 22% of the control after treatment with doxycycline at doses of 1 µg/ml and 10 µg/ml, respectively. Furthermore, a combination of progesterone and doxycycline showed an additive effect in low doses on the reduction of MMP-2 activity and pro-MMP2 expression in 12Z endometriotic cells. CONCLUSIONS: In conclusion, the MMP-inhibiting features of subantimicrobial-dose doxycycline may be further evaluated as a well-tolerable additional therapeutic approach, e.g. in combination with progestins such as dienogest, in patients with infiltrative endometriosis with insufficient response to current medical treatment options.

The use of home remedies and complementary health approaches in endometriosis.

RESEARCH QUESTION: Conventional treatments are often associated with adverse effects and endometriosis pain symptoms may reoccur despite treatment. Consequently, many women use complementary health approaches (CHA) and home remedies (HR) to relieve their pain. The aim of this study was to examine the frequency and the subjectively perceived efficacy of CHA/HR use by women affected by endometriosis. DESIGN: Retrospective evaluation using medical charts and a questionnaire. Women recruited in hospitals and in self-help groups were asked about the use of 'topical heat', 'repose/relaxation', 'movement/massages', 'homeopathy/phytotherapy', 'acupuncture/traditional Chinese medicine (TCM)' and 'kinesiology/physiotherapy'. RESULTS: From a total of 574 women with a confirmed diagnosis of endometriosis, 359 (62.5%) applied some form of CHA/HR. Women suffering from fatiguing disease symptoms more often selected alternative therapies (odds ratio [OR] 3.14, 95% confidence interval [CI] 1.39-7.11, P = 0.006) compared with women without these characteristics. Furthermore, women dissatisfied with healthcare provided by their treating physician, more frequently (OR 2.30, 95% CI 1.19-4.45, P = 0.013) chose the aforementioned alternative strategies. CONCLUSION: As conventional therapies may not be sufficiently effective, women's needs should be closely examined, and individual treatment options should be discussed and initiated by clinicians to provide the best comprehensive treatment possible for endometriosis.

The ENZIAN score as a preoperative MRI-based classification instrument for deep infiltrating endometriosis.

PURPOSE: Comparison of preoperative magnetic resonance imaging (MRI) with intraoperative findings in patients with deep infiltrating endometriosis (DIE) by means of the ENZIAN score. METHODS: This retrospective two-center study includes 63 patients with deep infiltrating endometriosis, who underwent surgery between 2012 and 2016 at both the University Hospital of Zurich and the Cantonal Hospital of Schaffhausen. Inclusion criteria were a preoperative pelvic MRI and intraoperative or bioptic confirmation of DIE. The preoperative MRI findings were compared with the intraoperative results by means of the ENZIAN score. Furthermore, the various MRI sequences were analyzed for their diagnostic value based on a Likert scale. RESULTS: Sensitivity and negative predictive values of MRI confirmed by surgery were 95.2% and 91.7% (lesions in the vaginal/rectovaginal space), 78.4% and 56% (uterosacral ligaments), 91.4% and 89.7% (rectum/sigmoid colon), 57.1% and 94.1% (myometrium), 85.7% and 98.3% (bladder), and 73.3% and 92.2% (intestine), respectively. T2 axial and sagittal MRI sequences in combination with a T1 sequence were diagnostically sufficient. CONCLUSIONS: The MRI-based ENZIAN score correlates well with the intraoperative findings, enabling a better planning of the surgical procedure for patients and physicians. However, considerable difficulty and a poorer comparability result from the variations in sequences used in the detection of this multifaceted disease. Therefore, a standardization of MRI protocols used in the detection of DIE will be a crucial step towards increased diagnostic validity and the ENZIAN score may be used as an anatomical land map and valuable communication tool between radiologists and gynecologists.

Fatigue - a symptom in endometriosis.

STUDY QUESTION: Is fatigue a frequent symptom of endometriosis? SUMMARY ANSWER: Fatigue is an underestimated symptom of endometriosis as it affects the majority of women with endometriosis, but it is not widely discussed in literature. WHAT IS KNOWN ALREADY: Fatigue can be a symptom of endometriosis causing major distress impacting the daily activities and quality of life of women with endometriosis. However, few studies with large sample sizes have investigated fatigue as a symptom of endometriosis. STUDY DESIGN, SIZE, DURATION: The study was designed as a multi-center matched case-control study. Recruitment took place at hospitals and private practices in Switzerland, Germany and Austria between 2010 and 2016. Data was collected from 1120 women, 560 of them with endometriosis. The women with endometriosis were matched to 560 control women in regard to age ±3 years and ethnic background. PARTICIPANTS/MATERIALS, SETTING, METHODS: Diagnosis of women with endometriosis had to be surgically and histologically confirmed. Surgical exclusion or absence of any endometriosis-identifying symptoms was required for control subjects. Materials included surgical and histological reports as well as data retrieved from a self-administered questionnaire. This study focused on the symptom fatigue in endometriosis. Relationships of variables were established by regression analysis and associations were quantified as odds ratios. MAIN RESULTS AND THE ROLE OF CHANCE: Frequent fatigue was experienced by a majority of women diagnosed with endometriosis (50.7% versus 22.4% in control women, P < 0.001). Fatigue in endometriosis was associated with insomnia (OR: 7.31, CI: 4.62-11.56, P < 0.001), depression (OR: 4.45, CI: 2.76-7.19, P < 0.001), pain (OR: 2.22, CI: 1.52-3.23, P < 0.001), and occupational stress (OR: 1.45, CI: 1.02-2.07, P = 0.037), but was independent of age, time since first diagnosis and stage of the disease. LIMITATIONS, REASONS FOR CAUTION: Women with asymptomatic endometriosis cannot be excluded in the control group which would lead to underestimation of our results. The study's design allows no evaluation of causal effects. WIDER IMPLICATIONS OF THE FINDINGS: As fatigue is experienced by numerous women with endometriosis, it needs to be addressed in the discussion of management and treatment of the disease. In addition to treating endometriosis, it would be beneficial to reduce insomnia, depression, pain and occupational stress in order to better manage fatigue. STUDY FUNDING/COMPETING INTEREST(S): There was no additional funding received for this study and no conflict of interest. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, NCT02511626.

Does Endometriosis Affect Sexual Activity and Satisfaction of the Man Partner? A Comparison of Partners From Women Diagnosed With Endometriosis and Controls.

BACKGROUND: Endometriosis-associated pain and dyspareunia influence female sexuality, but little is known about men's experiences in affected couples. AIM: To investigate how men partners experience sexuality in partnership with women with endometriosis. METHODS: A multi-center case-control study was performed between 2010 and 2015 in Switzerland, Germany, and Austria. 236 Partners of endometriosis patients and 236 partners of age-matched control women without endometriosis with a similar ethnic background were asked to answer selected, relevant questions of the Brief Index of Sexual Functioning and the Global Sexual Functioning questionnaire, as well as some investigator-derived questions. OUTCOMES: We sought to evaluate sexual satisfaction of men partners of endometriosis patients, investigate differences in sexual activities between men partners of women with and without endometriosis, and identify options to improve partnership sexuality in couples affected by endometriosis. RESULTS: Many partners of endometriosis patients reported changes in sexuality (75%). A majority of both groups was (very) satisfied with their sexual relationship (73.8% vs 58.1%, P = .002). Nevertheless, more partners of women diagnosed with endometriosis were not satisfied (P = .002) and their sexual problems more strongly interfered with relationship happiness (P = .001) than in partners of control women. Frequencies of sexual intercourse (P < .001) and all other partnered sexual activities (oral sex, petting) were significantly higher in the control group. The wish for an increased frequency of sexual activity (P = .387) and sexual desire (P = .919) did not differ statistically between both groups. CLINICAL TRANSLATION: There is a need to evaluate qualitative factors that influence sexual satisfaction in endometriosis patients. CONCLUSIONS: This is one of the first studies to investigate male sexuality affected by endometriosis. The meticulous verification of diagnosis and disease stage according to operation reports and histology allows for a high reliability of diagnosis. Our men's response rate of almost 50% is higher compared to other studies. Recruiting men through their woman partner may have caused selection bias. The adjustment to the specific situation in endometriosis by selecting questions from the Brief Index of Sexual Functioning and Global Sexual Functioning and adding investigator-derived questions likely influenced the validity of the questionnaires. Despite the fact that both partners of endometriosis patients and of control women largely reported high sexual satisfaction, there are challenges for some couples that arise in the context of a sexual relationship when one partner has endometriosis. Challenges such as sexuality-related pain or a reduced frequency of sexual activities should be addressed by health care professionals to ameliorate any current difficulties and to prevent the development or aggravation of sexual dysfunction. Hämmerli S, Kohl Schwartz AS, Geraedts K, et al. Does Endometriosis Affect Sexual Activity and Satisfaction of the Man Partner? A Comparison of Partners From Women Diagnosed With Endometriosis and Controls. J Sex Med 2018;15:853-865.

Pelvic Exenterations for Advanced and Recurrent Endometrial Cancer: Clinical Outcomes of 40 Patients.

OBJECTIVE: The aim of this study was to analyze the clinical experience and outcome of patients who have undergone pelvic exenteration for primary advanced or recurrent endometrial cancer. METHODS: We analyzed the medical records of 40 women who underwent pelvic exenteration to treat primary advanced or recurrent endometrial cancer. RESULTS: Pelvic exenteration was performed in 40 patients with primary advanced or recurrent endometrial cancer. Three patients (8%) underwent a primary exenteration, and 37 patients (92%) underwent a secondary exenteration. A total exenteration, anterior exenteration, and posterior exenteration was performed in 85%, 5%, and 10% of patients, respectively.In 31 cases, exenteration was performed with a curative aim, and in 9 cases, exenteration was performed with a palliative aim. The overall survival rates were 61.4% at 5 years and 51.1% at 10 years. For the 31 patients who underwent pelvic exenteration with a curative aim, the overall survival rates were higher than those for the entire study population and were 72.6% at 5 years and 59.4% at 10 years. For the 9 patients who underwent a palliative exenteration, the overall survival rates were 19.1% at 5 years and 0% at 10 years. This is to the best of our knowledge the biggest study of pelvic exenteration in patients with endometrial cancer. CONCLUSIONS: Our data show that pelvic exenterations are a valid therapeutic option with long-term survival in select patients.

The estrogen metabolites 2-methoxyestradiol and 2-hydroxyestradiol inhibit endometriotic cell proliferation in estrogen-receptor-independent manner.

Endometriosis, a painful disorder associated with infertility, is estimated to occur in approximately 7-10% of reproductive age women. Although endometriosis is considered as an estrogen-dependent disease, the role of estrogen metabolites via receptor-independent mechanisms has not yet been comprehensively clarified. In the present study, growth studies were performed comparing the effect of estradiol (E2), estrogen metabolites, that is, 2-hydroxyestradiol (2-OHE2) and 2-methoxyestradiol (2-ME), as well as estrogen-receptor-independent mechanisms using the estrogen receptor antagonist fulvestrant, on cell proliferation of endometriotic cells. The estrogen metabolites 2-OHE2 and 2-ME inhibited cell growth in a dose-dependent manner in pharmacological doses. Lower concentrations of 2-OHE2 had a stimulating effect on cell proliferation while pharmacologic doses exerted an antimitogenic effect. The effects on cell growth were at least partially receptor-independent, as demonstrated by simultaneous receptor antagonization with fulvestrant. In conclusion, our results demonstrate that in pharmacological doses the estrogen metabolites 2-ME and 2-OHE2 show inhibiting effects on the proliferation of endometriotic cells and may be promising substances for the treatment of endometriosis.

Investigating migraine phenotype and dynamics in women with endometriosis: an observational pilot study.

INTRODUCTION: Migraine and endometriosis are chronic disabling pain conditions. There is evidence for a shared genetic background. Migraine phenotype and course in patients with the comorbidity are insufficient investigated. Both conditions can be treated with progestins. METHODS: For this observational study we included women with migraine and endometriosis, visiting our clinic from 2015 to 2021. We collected available information from charts and complemented these data by a structured phone interview to collect more specific information on migraine and the course of both diseases. RESULTS: From 344 patients fulfilling the inclusion criteria, 94 suffered from both, endometriosis and migraine. Migraine with aura was reported by 41% of the patients and was associated with earlier onset of migraine (age < 17 years (OR 6.54) and with a history of medication overuse headache (OR 9.9, CI 1.6-59.4). Present monthly migraine frequency (1.5 ± 2.6) was significantly lower than five years before the interview (2.9 ± 4.64). There was a correlation between medication overuse headache and use of analgesics more than 3 days/months for dysmenorrhoea (p < 0.03). ASRM endometriosis score was not associated with migraine characteristics. CONCLUSIONS: We conclude that the comorbidity of endometriosis is highly linked to migraine with aura. Migraine onset in these patients was earlier. Further studies are needed to explore, if the observed decrease in migraine frequency can be attributed to recent endometriosis surgery and to understand if early diagnosis and treatment of both conditions may contribute to improve the course of both conditions. Trial registration BASEC Nr. 2021-00285.

Impact of family history for endometriosis, migraine, depression and early menopause on endometriosis symptoms, localization and stage: A case control study.

INTRODUCTION: Endometriosis is a common disabling pain condition in women of childbearing age, frequently showing familial clustering. Nevertheless, little is known about whether familial predispositions influence its severity or presentation. In this study, we investigate disease characteristics in endometriosis patients with a family history (FH) for endometriosis or the comorbidities migraine, depression and early menopause (EMP). MATERIALS AND METHODS: We performed an observational case-control study enrolling women with histologically confirmed endometriosis in a tertiary center. Based on surgical findings, patient records and phone interviews, we examined the relations between a FH for endometriosis, migraine, depression or EMP and endometriotic signs and symptoms, such as response to combined hormonal contraceptives (CHC) and analgesics, disease localization, infiltration depth, Enzian- and rASRM-scores. RESULTS: A positive FH for endometriosis, migraine, depression or EMP was reported by 10.2 %, 33.4 %, 32.6 % and 9.9 % of the 344 patients. A positive FH of endometriosis was associated with an increased risk for high rASRM-scores (rASRM 3 + 4: OR 2.74 (95 % CI 1.16-6.49), p = 0.017) and the presence of endometriomas (OR 2.70 (1.22-5.95), p = 0.011). A positive FH for migraine was associated with less response of endometriosis symptoms to CHC (OR 0.469 (0.27-0.82) p = 0.025). Depression in the family was linked to less severe rASRM-scores (rASRM 3 + 4: OR 0.63 (0.39-0.99), p = 0.046) and less endometriomas (OR 0.58 (0.67-0.92), p = 0.02), but increased the risk of both migraine (OR 1.66 (1.01-2.73), p = 0.043) and depression (OR 3.04 (1.89-4.89), p < 0.001) while showing a better response to CHC (OR 2.0 (1.15-3.48, p < 0.001). Patients with EMP in their family reported more current endometriosis symptoms at present (OR 3.72 (1.67-8.30), p = 0.001), more dysmenorrhea (OR 2.13 (1.04-4.35), p = 0.037), more frequent severe dysmenorrhea (OR 2.32 (1.14-4.74), p = 0.019) and suffered significantly more often > 5 days of non-cyclic pain (OR 3.58 (1.72-7.44), p < 0.001). CONCLUSIONS: Around 30% reported a positive FH for migraine or depression. Patients with a positive FH for endometriosis, migraine, depression or EMP differ in symptoms and surgical findings when compared to controls. While a FH for endometriosis is associated with higher rASRM scores and more endometriomas, women with a FH for depression had lower rASRM scores and less endometriomas while responding better to CHC. In contrast, women with a FH for migraine showed less response to CHC.

MRI-Based Radiomics as a Promising Noninvasive Diagnostic Technique for Adenomyosis.

Background: MRI diagnostics are important for adenomyosis, especially in cases with inconclusive ultrasound. This study assessed the potential of MRI-based radiomics as a novel tool for differentiating between uteri with and without adenomyosis. Methods: This retrospective proof-of-principle single-center study included nine patients with and six patients without adenomyosis. All patients had preoperative T2w MR images and histological findings served as the reference standard. The uterus of each patient was segmented in 3D using dedicated software, and 884 radiomics features were extracted. After dimension reduction and feature selection, the diagnostic yield of individual and combined features implemented in the machine learning models were assessed by means of receiver operating characteristics analyses. Results: Eleven relevant radiomics features were identified. The diagnostic performance of individual features in differentiating adenomyosis from the control group was high, with areas under the curve (AUCs) ranging from 0.78 to 0.98. The performance of ML models incorporating several features was excellent, with AUC scores of 1 and an area under the precision-recall curve of 0.4. Conclusions: The set of radiomics features derived from routine T2w MRI enabled accurate differentiation of uteri with adenomyosis. Radiomics could enhance diagnosis and furthermore serve as an imaging biomarker to aid in personalizing therapies and monitoring treatment responses.