Multicenter evaluation of blood-based biomarkers for the detection of endometriosis and adenomyosis: A prospective non-interventional study.

OBJECTIVE: To evaluate blood-based biomarkers to detect endometriosis and/or adenomyosis across nine European centers (June 2014-April 2018). METHODS: This prospective, non-interventional study assessed the diagnostic accuracy of 54 blood-based biomarker immunoassays in samples from 919 women (aged 18-45 years) with suspicion of endometriosis and/or adenomyosis versus symptomatic controls. Endometriosis was stratified by revised American Society for Reproductive Medicine stage. Symptomatic controls were "pathologic symptomatic controls" or "pathology-free symptomatic controls". The main outcome measure was receiver operating characteristic-area under the curve (ROC-AUC) and Wilcoxon P values corrected for multiple testing (q values). RESULTS: CA-125 performed best in "all endometriosis cases" versus "all symptomatic controls" (AUC 0.645, 95% confidence interval [CI] 0.600-0.690, q < 0.001) and increased (P < 0.001) with disease stage. In "all endometriosis cases" versus "pathology-free symptomatic controls", S100-A12 performed best (AUC 0.692, 95% CI 0.614-0.769, q = 0.001) followed by CA-125 (AUC 0.649, 95% CI 0.569-0.729, q = 0.021). In "adenomyosis only cases" versus "symptomatic controls" or "pathology-free symptomatic controls", respectively, the top-performing biomarkers were sFRP-4 (AUC 0.615, 95% CI 0.551-0.678, q = 0.045) and S100-A12 (AUC 0.701, 95% CI 0.611-0.792, q = 0.004). CONCLUSION: This study concluded that no biomarkers tested could diagnose or rule out endometriosis/adenomyosis with high certainty.

QS ENDO Pilot - A Study by the Stiftung Endometrioseforschung (SEF) on the Quality of Care Provided to Patients with Endometriosis in Certified Endometriosis Centers in the DACH Region.

Introduction Endometriosis significantly reduces patients' quality of life and is additionally a burden on healthcare and social security systems. There are currently no quality indicators for the treatment of endometriosis. The care of patients with endometriosis must be considered inadequate. QS ENDO aims to record the quality of care available in the DACH region and to introduce quality indicators for the diagnosis and treatment of endometriosis as part of providing quality assurance in endometriosis care. The first phase, QS ENDO Real, recorded the reality of current care using a questionnaire. The second phase, QS ENDO Pilot, investigated the treatment of 435 patients who underwent surgical treatment within a defined one month period in certified endometriosis centers. Material and Methods An online tool was used to gather information about 9 points which covered both prior patient history and the process of clinical diagnosis. Surgery reports were reviewed to obtain information about the surgical approach, the investigated sites, findings of any histological examinations, the use of classification systems, and information about resection status. Results 85.3% of patients were asked all 4 questions about their prior medical history. All 5 diagnostic steps were carried out in 34.5% of patients. The 3 areas needed to describe potential sites of disease were recorded in 67.1% of patients. Samples for histological examination were taken in 84.1% of patients. The endometriosis stage was classified in 94.7% of surgeries. A combination of the rASRM and the ENZIAN classifications, which is needed for complex cases, was used in 46.1% of patients. Complete resection was achieved in 81.6% of surgical procedures. Conclusion For the first time, the quality of care in certified endometriosis centers has been recorded using QS ENDO Pilot. Despite the high certification standards, a substantial number of required indicators were omitted.

Comparison of male and female perspective in couples involved in sexual relationships and facing endometriosis.

Background: While the sexuality of patients with endometriosis is an established topic in research, the possible effect of endometriosis on partnership sexuality has come to the fore only recently. To improve counseling, more information is needed on how both partners experience sexuality in the context of endometriosis. Aim: Previous research regarding endometriosis and sexuality normally focused on one partner to explore couples' intimate relations, whereas this study provides a comparison on both partners' perspectives on their common sexuality. Methods: An overall 302 couples received a questionnaire based on the Brief Index of Sexual Functioning and Sexual History Form, which was modified by endometriosis specialists to better focus on endometriosis-specific aspects. To detect different perspectives on common sexuality within the couple, the Wilcoxon test and the Pearson chi-square test were performed. Outcomes: Various aspects of couple sexuality were assessed by both partners to investigate divergent perspectives between the man and the woman within a couple. Results: On one hand, male and female partners seem to have divergent perspectives on sexual satisfaction in general, desired frequency of sexual contacts, and the question of the female partner engaging in sexual activity despite discomfort. On the other, they have similar perspectives on who takes initiative in sexual contacts, satisfaction with variety in the sexual relationship, and the impact of sexual limitations on their satisfaction within the partnership. Clinical implications: Endometriosis research addressing issues related to sexuality should include male partners; the same applies to consulting women with endometriosis in the context of their relationships rather than as individuals. Strengths and Limitations: This is the first analysis conducted on a larger scale of data from both partners in couples dealing with endometriosis. As it provides quantitative information only, some qualitative information remains unexplored. Conclusion: As both partners showed tendencies to overestimate their partners' sexual satisfaction and had different perspectives on sensitive topics in sexuality, such as the female partner engaging in sexual activity despite discomfort, addressing sexual communication could be a starting point in counseling couples dealing with endometriosis.

Effects of Vitamin D Supplementation on Surrogate Markers of Fertility in PCOS Women: A Randomized Controlled Trial.

Vitamin D (VD) might play an important role in polycystic ovary syndrome (PCOS) and female fertility. However, evidence from randomized controlled trials (RCT) is sparse. We examined VD effects on anti-Müllerian hormone (AMH) and other endocrine markers in PCOS and non-PCOS women. This is a post hoc analysis of a single-center, double-blind RCT conducted between December 2011 and October 2017 at the endocrine outpatient clinic at the Medical University of Graz, Austria. We included 180 PCOS women and 150 non-PCOS women with serum 25-hydroxyvitamin D (25(OH)D) concentrations <75 nmol/L in the trial. We randomized subjects to receive 20,000 IU of VD3/week (119 PCOS, 99 non-PCOS women) or placebo (61 PCOS, 51 non-PCOS women) for 24 weeks. Outcome measures were AMH, follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, dehydroepiandrosterone sulfate, and androstenedione. In PCOS women, we observed a significant treatment effect on FSH (mean treatment effect 0.94, 95% confidence interval [CI] 0.087 to 1.799, p = 0.031) and LH/FSH ratio (mean treatment effect -0.335, 95% CI -0.621 to 0.050, p = 0.022), whereas no significant effect was observed in non-PCOS women. In PCOS women, VD treatment for 24 weeks had a significant effect on FSH and LH/FSH ratio but no effect on AMH levels.

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.

QS ENDO Real - A Study by the German Endometriosis Research Foundation (SEF) on the Reality of Care for Patients with Endometriosis in Germany, Austria and Switzerland.

Endometriosis affects a significant number of young premenopausal women. Quite apart from the medical challenges, endometriosis is a relevant burden for healthcare and social security systems. Standardized quality indicators for the treatment of endometriosis have not previously been systematically verified. The three-stage study QS ENDO was initiated to record and improve the reality and quality of care. One of its aims is to create quality indicators for the diagnosis and treatment of endometriosis. For the first stage of QS ENDO Real, letters were sent to all 1014 gynecological departments in the German-speaking area of Europe (the DACH region) which included a questionnaire as a means of surveying the current state of care. A total of 296 (29.2%) of the centers which received the questionnaire participated in the survey. The subsequent evaluation of the completed questionnaires showed that the majority of patients with endometriosis (around 60%, based on estimates from the data) are not treated in hospitals which have been certified by the SEF. The guidelines recommend the use of specific classification systems (rASRM, ENZIAN) but, depending on the level of care offered by the hospital, only around 44.4 to 66.4% of departments used the rASRM score and only 27% of hospitals used the ENZIAN classification system to describe deep-infiltrating endometriosis. When taking patients' medical history, some centers (6.6 - 17.9%) considered questions about leading symptoms such as dyschezia, dysuria and dyspareunia to be unimportant. QS ENDO Real has made it possible, for the first time, to get an overview of the reality of care provided to patients with endometriosis in the German-speaking areas of Europe. The findings indicate that several of the measures recommended in international guidelines as the gold standard of care are only used to treat some of the patients. In this respect, more efforts will be needed to provide more advanced training. The approach used for treatment must be guideline-based, also in not-certified centers, to improve the quality of care in the treatment of patients with endometriosis.

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.

Effects of vitamin D supplementation on metabolic and endocrine parameters in healthy premenopausal women: A randomized controlled trial.

BACKGROUND & AIMS: Vitamin D supplementation may affect glycemic as well as hormonal regulation. Thus, the aim of the current study was to investigate whether vitamin D supplementation has any significant effects on metabolic and endocrine parameters in healthy premenopausal women. Primary outcome measure was the plasma glucose area under the curve (AUCgluc). METHODS: The current study was a single-center, double-blind, randomized placebo-controlled trial that was conducted at the Medical University of Graz, Austria, between March 2013 and October 2017. One-hundred and fifty healthy premenopausal women with 25-hydroxyvitamin D [25(OH)D] concentrations <75 nmol/L once weekly received either 20,000 IU of cholecalciferol or placebo (2:1 ratio) over a total of 24 weeks. RESULTS: In total, 127 women [age 36.2 ± 8.7 years; BMI 25.3 ± 5.6 kg/m2; baseline 25(OH)D 55.8 ± 19.7 nmol/L] completed the study. Vitamin D supplementation had no significant effect on AUCgluc (mean treatment effect 11.70; p = 0.069), while it had a significant treatment effect on homeostatic model assessment-insulin resistance (HOMA-IR; mean treatment effect 0.31; p = 0.019) and quantitative insulin-sensitivity check index (QUICKI; mean treatment effect -0.019; p = 0.013). There was no significant effect on the remaining secondary outcome parameters. CONCLUSIONS: In this randomized-controlled trial in healthy premenopausal women, there was a significant treatment effect of vitamin D supplementation on HOMA-IR and QUICKI, while there was no significant treatment effect on AUCgluc.

Effects of Vitamin D Supplementation on Body Composition and Metabolic Risk Factors in Men: A Randomized Controlled Trial.

Vitamin D might play a role in metabolic processes and obesity. We therefore examined vitamin D effects on metabolic markers and obesity in a randomized controlled trial (RCT). This is a post-hoc analysis of the Graz Vitamin D&TT-RCT, a single-center, double-blind, randomized placebo-controlled trial. We included 200 healthy men with serum 25-hydroxyvitamin D (25(OH) D) levels <75 nmol/L. Subjects received 20,000 IU of vitamin D3/week (n = 100) or placebo (n = 100) for 12 weeks. Outcome measures were metabolic markers, anthropometric measures, and body composition assessed by Dual-energy X-ray absorptiometry. One-hundred and ninety-two men completed the study. We found a significant treatment effect on fasting glucose/fasting insulin ratio (-5.3 (-10.4 to -0.2), p = 0.040), whereas we observed no significant effect on the remaining outcome parameters. In subgroup analyses of men with baseline 25(OH)D levels <50 nmol/L (n = 80), we found a significant effect on waist circumference (1.6 (0.3 to 2.9) cm, p = 0.012), waist-to-hip ratio (0.019 (0.002 to 0.036), p = 0.031), total body fat (0.029 (0.004 to 0.055) %, p = 0.026), and android fat (1.18 (0.11 to 2.26) %, p = 0.010). In middle-aged healthy men, vitamin D treatment had a negative effect on insulin sensitivity. In vitamin D deficient men, vitamin D has an unfavorable effect on central obesity and body composition.

Effects of Vitamin D Supplementation on Bone Turnover and Bone Mineral Density in Healthy Men: A Post-Hoc Analysis of a Randomized Controlled Trial.

Vitamin D is well known for its effects on calcium and mineral metabolism. However, vitamin D effects on bone turnover markers (BTMs), which are used together with bone mineral density (BMD) to evaluate bone health, are less clear. We therefore examined vitamin D effects on BTMs (beta-cross laps (CTX) and osteocalcin (OC)) and BMD in a post-hoc analysis of a randomized controlled trial (RCT). This is a post-hoc analysis of the Graz Vitamin D&TT-RCT, a single-center, double-blind, randomized placebo-controlled trial conducted between December 2012 and November 2017 at the endocrine outpatient clinic at the Medical University of Graz, Austria. A total of 200 healthy men with serum 25-hydroxyvitamin D (25(OH)D) levels <75 nmol/L participated in the trial. Subjects were randomized to receive 20,000 IU of vitamin D3/week (n = 100) or placebo (n = 100) for 12 weeks. Outcome measures were BTMs, BMD, and trabecular bone score (TBS). A total of 192 men (mean age and 25(OH)D: 43 (±13) years and 54.9 (±18.3) nmol/L, respectively) completed the study. We found no significant treatment effect on BTMs, BMD, or TBS (p > 0.05 for all). In middle-aged healthy men, vitamin D treatment for 12 weeks had no significant effect on BTMs or BMD.

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.

Effects of vitamin D supplementation on metabolic and endocrine parameters in PCOS: a randomized-controlled trial.

PURPOSE: Vitamin D status may be associated with insulin resistance and other key features of polycystic ovary syndrome (PCOS), but data from preliminary randomized controlled trials (RCTs) are conflicting. Therefore, we aimed to investigate the effects of vitamin D supplementation on plasma glucose area under the curve (AUCgluc, primary outcome measure) and on other metabolic and endocrine parameters (secondary outcome measures). METHODS: This study was a single-center, double-blind, randomized placebo-controlled trial conducted between December 2011 and July 2017 at the Medical University of Graz, Austria. One-hundred and eighty women with PCOS and 25-hydroxyvitamin D [25(OH)D] concentrations < 75 nmol/L were randomized in a 2:1 ratio to either receive 20,000 IU of cholecalciferol weekly or placebo over 24 weeks. Primary outcome was the between-group difference in AUCgluc at study end while adjusting for baseline values. RESULTS: In total, 123 participants completed the study [age 25.9 ± 4.7 years; BMI 27.5 ± 7.3 kg/m2; baseline 25(OH)D 48.8 ± 16.9 nmol/L, baseline fasting glucose 84 ± 8 mg/dL]. Vitamin D supplementation lead to a significant increase in 25(OH)D [mean treatment effect 33.4 nmol/L; 95% confidence interval (CI) 24.5 to 42.2; p < 0.001] but had no significant effect on AUCgluc (mean treatment effect - 9.19; 95% CI - 21.40 to 3.02; p = 0.139). Regarding secondary outcome measures, we observed a significant decrease in plasma glucose at 60 min during oral glucose tolerance test (mean treatment effect - 10.2 mg/dL; 95% CI - 20.2 to - 0.3; p = 0.045). CONCLUSIONS: Vitamin D supplementation had no significant effect on metabolic and endocrine parameters in PCOS with the exception of a reduced plasma glucose during OGTT.

Effects of vitamin D supplementation on androgens in men with low testosterone levels: a randomized controlled trial.

PURPOSE: It has been hypothesized that vitamin D is associated with androgen levels in men. We, therefore, aimed to evaluate whether vitamin D supplementation increases serum total testosterone (TT) levels in men with low TT levels at baseline. METHODS: The Graz Vitamin D&TT-RCT is a single-center, double-blind, randomized placebo-controlled trial conducted between March 2013 and November 2017 at the endocrine outpatient clinic at the Medical University of Graz, Austria. One-hundred healthy men with serum TT levels < 10.4 nmol/l and 25-hydroxyvitamin D [25(OH)D] levels < 75 nmol/l participated in the trial. Subjects were randomized to receive 20,000 IU of vitamin D3/week (n = 50) or placebo (n = 50) for 12 weeks. Primary outcome was TT measured using mass spectrometry. Secondary outcomes were free testosterone, free androgen index, sex hormone-binding globulin, estradiol, follicle-stimulating hormone, luteinizing hormone, metabolic characteristics, and body composition. RESULTS: Ninety-four men [mean age and 25(OH)D: 47 (± 12) years and 56.3 (± 18.3) nmol/l, respectively] completed the study. We found no significant treatment effect on serum TT or on the remaining secondary outcome variables. CONCLUSION: Vitamin D treatment had no effect on serum TT levels in middle-aged healthy men with low TT levels.

Satisfaction with medical support in women with endometriosis.

Endometriosis affects various aspects of women's lives. We searched for predictors for patient satisfaction with medical support (PSwMS) in women with endometriosis. The study was designed as a multi-centre retrospective cohort study. We approached women with histologically confirmed endometriosis from 2010 until 2016, comparing women satisfied to women dissatisfied with medical support. We analysed data on characteristics of endometriosis, PSwMS and the influence of disease characteristics on PSwMS. Information on satisfaction with medical support was collected through a standardized questionnaire. After exclusion of 73 women because of inchoately filled in questionnaires, data from 498 women was evaluated. Altogether, it was observed that 54.6% (n = 272) of the study participants were satisfied with medical support and 45.4% (n = 226) were not. Feeling adequately informed by the time of diagnosis (p < 0.001), taking women's mental troubles seriously (p < 0.001) and supporting women in handling their pain (p < 0.001) were significantly associated with satisfaction. We found adequate information to be the most distinctive indicator for PSwMS. Further, acknowledging psychological distress and supporting women in handling their symptoms rather than to alleviate them, positively affect PSwMS. To achieve PSwMS, healthcare providers have to give adequate information on endometriosis and its management.

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.

Endometriosis, especially mild disease: a risk factor for miscarriages.

OBJECTIVE: To investigate the prevalence of miscarriage in women with endometriosis (WwE) compared with disease-free control women (CW). DESIGN: Cross-sectional analysis nested in a retrospective observational study (n = 940). SETTING: Hospitals and associated private practices. PATIENT(S): Previously pregnant women (n = 268) within reproductive age in matched pairs. INTERVENTION(S): Retrospective analysis of surgical reports and self-administered questionnaires. MAIN OUTCOME MEASURE(S): Rate of miscarriage, subanalysis for fertility status (≤12 vs. >12 months' time to conception), endometriosis stages (revised American Society of Reproductive Medicine classification [rASRM] I/II vs. III/IV) and phenotypic localizations (superficial peritoneal, ovarian, and deep infiltrating endometriosis). RESULT(S): The miscarriage rate was higher in WwE (35.8% [95% confidence interval 29.6%-42.0%]) compared with CW (22.0% [16.7%-27.0%]); adjusted incidence risk ratio of 1.97 (95% CI 1.41-2.75). This remained significant in subfertile WwE (50.0% [40.7%-59.4%]) vs. CW (25.8% [8.5%-41.2%]) but not in fertile WwE (24.5% [16.3%-31.6%]) vs. CW (21.5% [15.9%-26.8%]). The miscarriage rate was higher in women with milder forms (rASRM I/II 42.1% [32.6%-51.4%] vs. rASRM III/IV 30.8% [22.6%-38.7%], compared with 22.0% [16.7%-27.0%] in CW), and in women with superficial peritoneal endometriosis (42.0% [32.0%-53.9%]) compared with ovarian endometriosis (28.6% [17.7%-38.7%]) and deep infiltrating endometriosis (33.9% [21.2%-46.0%]) compared with CW (22.0% [16.7%-27.0%]). CONCLUSION(S): Mild endometriosis, as in superficial lesions, is related to a great extent of inflammatory disorder, possibly leading to defective folliculogenesis, fertilization, and/or implantation, presenting as increased risk of miscarriage. CLINICAL TRIAL REGISTRATION NUMBER: NCT02511626.

Altered expression of progesterone receptor isoforms A and B in human eutopic endometrium in endometriosis patients.

Recent data implicate an altered expression of progesterone receptor isoform A (PR-A) and B (PR-B) in the endometrium of endometriosis patients. This prospective exploratory study aimed to precisely determine the PR-A and PR-B expression using immunohistochemical techniques in eutopic endometrium of women with endometriosis compared with disease-free women throughout the menstrual cycle. All symptomatic patients underwent laparoscopy for the diagnosis of endometriosis and histological confirmation of the disease (EO) whereas controls were proven disease-free (CO). In CO samples (n=10) an increased expression of PR-A and PR-B during the proliferative to early secretory phase and a decreased expression of both receptor isoforms during the mid to late secretory phase was ascertained in accordance with previous studies. In patients with endometriosis (n=16) no cycle dependent pattern of PR-A and PR-B expression was identified in contrast to patients without endometriosis. Moreover, in EO samples a huge variety of inter- and intra-individual differences in PR-A and PR-B expression were detected. These data provide further evidence that dysregulation of the PR-A and PR-B expression might contribute to the pathophysiology of endometriosis.

When sex is not on fire: a prospective multicentre study evaluating the short-term effects of radical resection of endometriosis on quality of sex life and dyspareunia.

OBJECTIVE: The aim of the current study was to evaluate the effect of surgical removal of endometriosis on dyspareunia, sexual function, quality of sex life and interpersonal relationships. STUDY DESIGN: A questionnaire-based multicentre prospective study was conducted in six tertiary referral centres in Austria and Germany. Ninety-six patients with histologically proven endometriosis and dyspareunia were included. Before surgery and averagely 10 months postoperatively (range 9-12 months), the Female Sexual Function Index (FSFI) and the Female Sexual Distress Scale (FSDS) were used to screen women's sexuality. Additionally, we evaluated psychological parameters and pain intensity during/after sexual intercourse via a self-administered questionnaire. RESULTS: Pain scores measured via NAS during/after intercourse decreased significantly after surgery. Frequencies of interrupted sexual intercourse, feelings of guilt towards the partner, being afraid of pain before/during sexual intercourse and feelings of being a burden for the relationship also decreased significantly in patients with peritoneal endometriosis and deep infiltrating endometriosis. Interestingly, sexually related personal distress did not improve in women with peritoneal endometriosis/vaginal resection, but improved in cases of deep infiltrating endometriosis (DIE). CONCLUSION: Radical laparoscopic excision of endometriosis offers an effective treatment option and offers a significant improvement in dyspareunia and quality of sex life.

Hematopoietic stem and progenitor cells acquire distinct DNA-hypermethylation during in vitro culture.

Hematopoietic stem and progenitor cells (HPCs) can be maintained in vitro, but the vast majority of their progeny loses stemness during culture. In this study, we compared DNA-methylation (DNAm) profiles of freshly isolated and culture-expanded HPCs. Culture conditions of CD34(+) cells - either with or without mesenchymal stromal cells (MSCs) - had relatively little impact on DNAm, although proliferation is greatly increased by stromal support. However, all cultured HPCs - even those which remained CD34(+) - acquired significant DNA-hypermethylation. DNA-hypermethylation occurred particularly in up-stream promoter regions, shore-regions of CpG islands, binding sites for PU.1, HOXA5 and RUNX1, and it was reflected in differential gene expression and variant transcripts of DNMT3A. Low concentrations of DNAm inhibitors slightly increased the frequency of colony-forming unit initiating cells. Our results demonstrate that HPCs acquire DNA-hypermethylation at specific sites in the genome which is relevant for the rapid loss of stemness during in vitro manipulation.