Search

Pericytes (PCs) contribute to brain capillary/BBB integrity and PC migration is a hallmark for brain capillary leakage following pro-inflammatory insults. Estradiol promotes endothelial barrier integrity by inhibiting tumor necrosis factor-alpha (TNF-α)-induced PC migration. However, the underlying mechanisms remain unclear. Since micro-RNAs (miRs) regulate BBB integrity and increases in miR638 and TNF-α occur in pathological events associated with capillary leakage, we hypothesize that TNF-α mediates its capillary disruptive actions via miR638 and that estradiol blocks these actions. Using quantitative reverse transcription PCR, we first assessed the modulatory effects of TNF-α on miR638. The treatment of PCs with TNF-α significantly induced miR638. Moreover, transfection with miR638 mimic induced PC migration, whereas inhibitory miR638 (anti-miR) abrogated the pro-migratory actions of TNF-α, suggesting that TNF-α stimulates PC migration via miR638. At a molecular level, the pro-migratory effects of miR638 involved the phosphorylation of ERK1/2 but not Akt. Interestingly, estradiol downregulated the constitutive and TNF-α-stimulated expression of miR638 and inhibited the TNF-α-induced migration of PCs. In PCs treated with estrogen receptor (ER) ER-α, ER-β, and GPR30 agonists, a significant downregulation in miR638 expression was solely observed in response to DPN, an ER-β agonist. DPN inhibited the pro-migratory effects of TNF-α but not miR638. Additionally, the ectopic expression of miR638 prevented the inhibitory effects of DPN on TNF-α-induced PC migration, suggesting that interference in miR638 formation plays a key role in mediating the inhibitory actions of estradiol/DPN. In conclusion, these findings provide the first evidence that estradiol inhibits TNF-α-induced PC migration by specifically downregulating miR638 via ER-β and may protect the neurovascular unit during injury/stroke via this mechanism. [ABSTRACT FROM AUTHOR]

Introduction: Partnership is an important resource in dealing with endometriosis related chronic pain. Hence, our objective was to assess partnership in the context of endometriosis and its symptoms, considering the perspectives of both individuals involved. Methods: The study was designed as a multi-center matched case-control study in Switzerland, Germany and Austria. Altogether 381 women with surgically/histologically confirmed endometriosis and 381 control women, 250 male partners of endometriosis-affected women and 229 of control women were evaluated. Partnership quality, partnership happiness, separation thoughts, and areas of conflict were evaluated through the Partnership Questionnaire and a validated list of conflict areas. Results: Quality of partnership was rated as high by 60.1% of the women with endometriosis and 66.7% of the control women, as well as by 45.8 and 50.2% of their respective partners. Women with endometriosis mentioned separation thoughts, mostly related to sexual satisfaction, more often (34.9%/28.3%) and experienced more partnership-related conflicts than control women. Chronic pain, dyspareunia, dissatisfaction with sexuality, fatigue, and infertility were significantly associated with partnership conflicts. Fatigue and infertility but not pain experiences were related to lower partnership quality. Male partners in both groups reported separation thoughts equally often. In men, a high intensity of pain experienced by their partner was associated with reduced partnership happiness. Conclusion: Given the significance of partnership in dealing with chronic diseases and the connection between symptoms of endometriosis and a decrease in partnership quality, it is essential to incorporate strategies that alleviate the negative impacts on relationships for both partners into medical support. [ABSTRACT FROM AUTHOR]

To better understand the physiological basis of obesity in women, we investigated whether obesity or menstrual cycle phase affects laboratory test-meal size or meal-stimulated plasma cholecystokinin (CCK) concentration. Women with healthy weight (body mass index [BMI] of 18.5-24.9 kg/m2, N = 16) or obesity (BMI 30-39.9 kg/m2, N = 20) were tested once in the late-follicular or peri-ovulatory phase (LF/PO) and once in the mid-luteal phase (ML). Meals of ham sandwiches were offered and blood was sampled. Menstrual cycle phases were verified with participants' reports of menses and measurements of progesterone and luteinizing hormone (LH) concentrations. Women with obesity ate significantly larger meals than women with healthy weight, (mean, 711 [95% CI, 402-1013] kJ, P = 0.001, during the LF/PO and 426 [105-734] kJ, P = 0.027, larger during the ML). Women with healthy weight ate smaller meals during LF/PO than ML (decrease, 510 [192-821 kJ], P = 0.008), but women with obesity did not (decrease, 226 [−87-542] kJ, P = 0.15). CCK concentrations 18 to 30 minutes after meal onset were lower in women with obesity than in women with healthy weight during LF/PO (3.6 [3.1-4.1] vs 6.1 [4.5-7.7] pmol/L; P = 0.004), but not during ML, with a significant interaction effect (1.8 [1.2-2.4] pmol/L, P = 0.048). Women with obesity consumed larger meals than women with healthy weight but displayed reduced meal-stimulated plasma CCK concentrations. These data are consistent with the hypothesis that a defect in CCK secretion compromises satiation in obese women and contributes to the development or maintenance of obesity. [ABSTRACT FROM AUTHOR]

Background: Genital pain treatment regimens range from local or systemic pharmacological to non-pharmacological, manual and psychosexual therapies with poor to moderate evidence for their efficiency. The aim of this study was to evaluate the subjective therapeutic response (genital pain relief) of different treatment modalities for vulvodynia and the most prevalent other vulvar pathologies, chronic vulvar eczema and lichen sclerosus by means of a cross-sectional survey. Material and Methods: A questionnaire-based cohort study that included 128 vulvodynia, 116 eczema and 79 lichen sclerosus patients was used. All patients attended the vulvar clinic at the University Hospital of Zurich. The patients who had been treated were surveyed from January to October 2022, using a customized online questionnaire consisting of 37 questions on symptoms and treatment outcomes for guideline-recommended treatment modalities. The study was approved by the Cantonal Ethics Review Board of Zurich. Results: Altogether, 41 patients with vulvodynia, 37 with vulvar eczema and 23 with lichen sclerosus returned the questionnaire. The three groups were similar regarding pain characteristics and comorbidities. All three patient groups reported having benefited from non-pharmacological treatment (improvement rate vulvodynia 54%; eczema 51%; lichen sclerosus 58%), from topical (55%; 55%; 75%) and from locally invasive (46%; 66%; 50%) treatments. Overall, there was no significant difference in subjective treatment outcome between non-pharmacological, locally invasive, and topical treatments for vulvodynia, eczema, and lichen sclerosus. However, the use of oral medication was reported to be significantly less effective (p-value 0.050). Conclusion: In conclusion, we found that in the patients' perception, topical, invasive and non-pharmacological treatments, but not oral medications, are helpful for genital pain relief in women with vulvodynia, vulvar eczema, and lichen sclerosus. Therefore, we recommend an escalating therapy approach with first-line non-pharmacological treatments together with topical therapies. [ABSTRACT FROM AUTHOR]

The abnormal growth of oligodendrocyte precursor cells (OPCs) significantly contributes to the progression of glioblastoma tumors. Hence, molecules that block OPC growth may be of therapeutic importance in treating gliomas. 2-Methoxyestradiol (2ME), an endogenous tubulin-interacting metabolite of estradiol, is effective against multiple proliferative disorders. Based on its anti-carcinogenic and anti-angiogenic actions, it is undergoing phase II clinical trials. We hypothesize that 2ME may prevent glioma growth by targeting OPC growth. Here, we tested this hypothesis by assessing the impact of 2ME on the growth of an OPC line, "Oli-neu", and dissected the underlying mechanism(s). Treatment with 2ME inhibited OPC growth in a concentration-dependent manner, accompanied by significant upregulation in the expression of p21 and p27, which are negative cell-cycle regulators. Moreover, treatment with 2ME altered OPC morphology from multi-arm processes to rounded cells. At concentrations of 1uM and greater, 2ME induced apoptosis, with increased expressions of caspase 3, PARP, and caspase-7 fragments, externalized phosphatidylserine staining/APOPercentage, and increased mitochondrial activity. Flow cytometry and microscopic analysis demonstrated that 2ME triggers endoreduplication in a concentration-dependent fashion. Importantly, 2ME induced cyclin E, JNK1/2, and p53 expression, as well as OPC fusion, which are key mechanisms driving endoreduplication and whole-genome duplication. Importantly, the inhibition of p53 with pifithrin-α rescued 2ME-induced endoreduplication. The pro-apoptotic and endoreduplication actions of 2ME were accompanied by the upregulation of survivin, cyclin A, Cyclin B, Cyclin D2, and ppRB. Similar growth inhibitory, apoptotic, and endoreduplication effects of 2ME were observed in CG4 cells. Taken together, our findings provide evidence that 2ME not only inhibits OPC growth and triggers apoptosis, but also activates OPCs into survival (fight or flight) mode, leading to endoreduplication. This inherent survival characteristic of OPCs may, in part, be responsible for drug resistance in gliomas, as observed for many tubulin-interacting drugs. Importantly, the fate of OPCs after 2ME treatment may depend on the cell-cycle status of individual cells. Combining tubulin-interfering molecules with drugs such as pifithrin-α that inhibit endoreduplication may help inhibit OPC/glioma growth and limit drug resistance. [ABSTRACT FROM AUTHOR]

Endothelial progenitor cells (EPCs) play a critical role in cardiovascular regeneration. Enhancement of their native properties would be highly beneficial to ensuring the proper functioning of the cardiovascular system. As androgens have a positive effect on the cardiovascular system, we hypothesized that dihydrotestosterone (DHT) could also influence EPC-mediated repair processes. To evaluate this hypothesis, we investigated the effects of DHT on cultured human EPCs' proliferation, viability, morphology, migration, angiogenesis, gene and protein expression, and ability to integrate into cardiac tissue. The results showed that DHT at different concentrations had no cytotoxic effect on EPCs, significantly enhanced the cell proliferation and viability and induces fast, androgen-receptor-dependent formation of capillary-like structures. DHT treatment of EPCs regulated gene expression of androgen receptors and the genes and proteins involved in cell migration and angiogenesis. Importantly, DHT stimulation promoted EPC migration and the cells' ability to adhere and integrate into murine cardiac slices, suggesting it has a role in promoting tissue regeneration. Mass spectrometry analysis further highlighted the impact of DHT on EPCs' functioning. In conclusion, DHT increases the proliferation, migration, and androgen-receptor-dependent angiogenesis of EPCs; enhances the cells' secretion of key factors involved in angiogenesis; and significantly potentiates cellular integration into heart tissue. The data offer support for potential therapeutic applications of DHT in cardiovascular regeneration and repair processes. [ABSTRACT FROM AUTHOR]

Background: The impact of sexual abstinence on sperm quality, particularly in pathological cases, is a subject of debate. We investigated the link between abstinence duration and semen quality in both normal and pathological samples. Methods: We analyzed semen samples from 4423 men undergoing fertility evaluation, comprising 1256 samples from healthy individuals and 3167 from those with conditions such as oligozoospermia, asthenozoospermia, teratozoospermia, or a combination of these factors, namely oligoasthenoteratozoospermia (OAT). Parameters including sperm concentration, the percentage of progressively motile spermatozoa, total motile sperm count, and the percentage of spermatozoa with normal morphology were assessed at various abstinence durations (each day, 0–2, 3–7, and >7 days). Results: Extended abstinence correlated with higher sperm concentration overall (p < 0.001), except in oligozoospermia. Longer abstinence reduced progressive motility in normal (p < 0.001) and teratozoospermic samples (p < 0.001). Shorter abstinence was linked to higher morphologically normal sperm in normal samples (p = 0.03), while longer abstinence did so in oligoasthenoteratozoospermic samples (p = 0.013). Conclusion: The findings suggest that a prolonged abstinence time is linked to higher sperm concentration, while optimal sperm motility is observed after shorter abstinence periods. However, results regarding morphology remain inconclusive. Recommendations on abstinence duration should be tailored based on the specific parameter requiring the most significant improvement. [ABSTRACT FROM AUTHOR]

To better understand the physiological basis of obesity in women, we investigated whether obesity or menstrual cycle phase affects laboratory test-meal size or meal-stimulated plasma cholecystokinin (CCK) concentration. Women with healthy weight (body mass index [BMI] of 18.5-24.9 kg/m2, N = 16) or obesity (BMI 30-39.9 kg/m2, N = 20) were tested once in the late-follicular or peri-ovulatory phase (LF/PO) and once in the mid-luteal phase (ML). Meals of ham sandwiches were offered and blood was sampled. Menstrual cycle phases were verified with participants' reports of menses and measurements of progesterone and luteinizing hormone (LH) concentrations. Women with obesity ate significantly larger meals than women with healthy weight, (mean, 711 [95% CI, 402-1013] kJ, P = 0.001, during the LF/PO and 426 [105-734] kJ, P = 0.027, larger during the ML). Women with healthy weight ate smaller meals during LF/PO than ML (decrease, 510 [192-821 kJ], P = 0.008), but women with obesity did not (decrease, 226 [−87-542] kJ, P = 0.15). CCK concentrations 18 to 30 minutes after meal onset were lower in women with obesity than in women with healthy weight during LF/PO (3.6 [3.1-4.1] vs 6.1 [4.5-7.7] pmol/L; P = 0.004), but not during ML, with a significant interaction effect (1.8 [1.2-2.4] pmol/L, P = 0.048). Women with obesity consumed larger meals than women with healthy weight but displayed reduced meal-stimulated plasma CCK concentrations. These data are consistent with the hypothesis that a defect in CCK secretion compromises satiation in obese women and contributes to the development or maintenance of obesity. [ABSTRACT FROM AUTHOR]

(1) Background: Hormonal fluctuations across the menstrual cycle lead to multiple changes in physiological parameters such as body temperature, cardiovascular function, respiratory rate and perfusion. Electronic wearables analyzing those parameters might present a convenient alternative to urinary ovulation tests for predicting the fertile window. (2) Methods: We conducted a prospective observational study including women aged 18–45 years without current hormonal therapy who used a wrist-worn medical device and urinary ovulation tests for a minimum of three cycles. We analyzed the accuracy of both the retrospective and prospective algorithms using a generalized linear mixed-effects model. The findings were compared to real-world data from bracelet users who also reported urinary ovulation tests. (3) Results: A total of 61 study participants contributing 205 cycles and 6081 real-life cycles from 3268 bracelet users were included in the analysis. The mean error in identifying ovulation with the wrist-worn medical device retrospective algorithm in the clinical study was 0.31 days (95% CI −0.13 to 0.75). The retrospective algorithm identified 75.4% of fertile days, and the prospective algorithm identified 73.8% of fertile days correctly within the pre-specified equivalence limits (±2 days). The quality of the retrospective algorithm in the clinical study could be confirmed by real-world data. (4) Conclusion: Our data indicate that wearable sensors may be used to accurately detect the periovulatory period. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the use of wearable sensors for prediction of intraamniotic infection in pregnant women with PPROM. Materials and methods: In a prospective proof of principle study, we included 50 patients diagnosed with PPROM at the University Hospital Zurich between November 2017 and May 2020. Patients were instructed to wear a bracelet during the night, which measures physiological parameters including wrist skin temperature, heart rate, heart rate variability, and breathing rate. A two-way repeated measures ANOVA was performed to evaluate the difference over time of both the wearable device measured parameters and standard clinical monitoring values, such as body temperature, pulse, leucocytes, and C-reactive protein, between women with and without intraamniotic infection. Results: Altogether, 23 patients (46%) were diagnosed with intraamniotic infection. Regarding the physiological parameters measured with the bracelet, we observed a significant difference in breathing rate (19 vs 16 per min, P <.01) and heart rate (72 vs 67 beats per min, P =.03) in women with intraamniotic infection compared to those without during the 3 days prior to birth. In parallel to these changes standard clinical monitoring values were significantly different in the intraamniotic infection group compared to women without infection in the 3 days preceding birth. Conclusion: Our results suggest that wearable sensors are a promising, noninvasive, patient friendly approach to support the early detection of intraamniotic infection in women with PPROM. However, confirmation of our findings in larger studies is required before implementing this technique in standard clinical management. [ABSTRACT FROM AUTHOR]

Copyright of Gynäkologische Endokrinologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction: Recent evidence shows that endometriosis, a significant cause of infertility, may already present in adolescents. Dysmenorrhea, often leading to school absences, is a key symptom of the maturing menstrual cycle but also of endometriosis. However, it is often perceived as "normal" and left untreated. In adolescents, laparoscopy, the standard procedure to diagnose endometriosis, is performed particularly cautiously. To improve reproductive health in adolescents, we evaluate associations between early menstrual experiences and endometriosis. Methods: Retrospective data on early menstrual experiences from 563 women with surgically/histologically verified endometriosis and from 563 age-matched controls were compared. Study participants were recruited in Switzerland, Germany, and Austria. Information on menstrual experiences was collected via a structured questionnaire. Results: The bivariate analysis showed that early menarche (p = 0.004), dysmenorrhea and negative memories of menarche (p < 0.001) were significantly associated with a diagnosis of endometriosis. After controlling for confounders in bivariate regression analysis occurrence of dysmenorrhea (p = <0.001, OR 5,74, 95% CI 3.82-7.22) especially with onset >3 years after menarche ((p = <0.001, OR 3.42, 95% CI 2.09-5.64) remained statistically significant predictors for diagnosis of endometriosis. Dysmenorrhea in mothers and mothers' perceived attitude towards menstruation were not associated with the occurrence of Endometriosis. Conclusions: Dysmenorrhea and onset of dysmenorrhea at menarche or several years after it are strongly associated with the development of endometriosis. As mothers perceived attitudes towards menstruation show no significant association with their daughters' experiences, physical symptoms accompanying menarche and menstrual period pain in adolescents seem to be very reliable predictors in diagnosis of endometriosis. Therefore, dysmenorrhea in adolescents requires careful investigation of possible endometriosis, especially if it does not respond to medical management. [ABSTRACT FROM AUTHOR]

(1) Background: Basic vital signs change during normal pregnancy as they reflect the adaptation of maternal physiology. Electronic wearables like fitness bracelets have the potential to provide vital signs continuously in the home environment of pregnant women. (2) Methods: We performed a prospective observational study from November 2019 to November 2020 including healthy pregnant women, who recorded their wrist skin temperature, heart rate, heart rate variability, and breathing rate using an electronic wearable. In addition, eight emotions were assessed weekly using five-point Likert scales. Descriptive statistics and a multivariate model were applied to correlate the physiological parameters with maternal emotions. (3) Results: We analyzed data from 23 women using the electronic wearable during pregnancy. We calculated standard curves for each physiological parameter, which partially differed from the literature. We showed a significant association of several emotions like feeling stressed, tired, or happy with the course of physiological parameters. (4) Conclusions: Our data indicate that electronic wearables are helpful for closely observing vital signs in pregnancy and to establish modern curves for the physiological course of these parameters. In addition to physiological adaptation mechanisms and pregnancy disorders, emotions have the potential to influence the course of physiological parameters in pregnancy. [ABSTRACT FROM AUTHOR]

During the first 3 months of the coronavirus disease 2019 (COVID-19) pandemic, our hospital's quality management team determined a decline in the rate of cesarean deliveries (CD). Thus, in this study we examined both the factors associated with this decrease as well as neonatal outcomes. This was a retrospective observational cohort study comparing deliveries (n=597) between March and May 2020 (first nationwide "lockdown" in Switzerland) with those during the same period in 2018 and 2019 (n=1,063). A multivariable logistic regression analysis was used to examine the association between CD and the pandemic, adjusting for relevant risk factors for CD. The overall rate of CD during the pandemic period was lower (30.0%), than during the pre-pandemic period (38.7%, unadjusted odds ratio 0.68, 95% confidence interval [95%CI]: 0.55 to 0.84, p=0.0004) a result that was supported by the adjusted odds ratio (0.73, 95%CI: 0.54 to 0.99, p=0.04). The results of this study confirmed a significant reduction in the rate of CD in early 2020, during the first lockdown period due to COVID-19, but without major differences in maternal and infant health indicators or in obstetric risk factors than before the pandemic. These results may have been due to a difference in the composition of the obstetric team as well as the behavior of the obstetrics team and in the patients during the pandemic, given the burden it placed on healthcare systems. However, this hypothesis remains to be tested in further research. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

MicroRNA 193a-3p (miR193a-3p) is a short non-coding RNA with tumor suppressor properties. Breast cancer (BC) progression is governed by active interaction between breast cancer cells, vascular (V)/lymphatic (L) endothelial cells (ECs), and BC secretome. We have recently shown that miR193a-3p, a tumor suppressor miRNA, inhibits MCF-7 BC cell-driven growth of VECs via direct antimitogenic actions and alters MCF-7 secretome. Since LEC-BC cross-talk plays a key role in BC progression, we investigated the effects of miR193a-3p on MCF-7 secretome and estradiol-mediated growth effects in LECs and LEC + MCF-7 spheroids, and delineated the underlying mechanisms. Transfection of LECs with miR193a-3p, as well as secretome from MCF-7 transfected cells, inhibited LEC growth, and these effects were mimicked in LEC + MCF-7 spheroids. Moreover, miR193a-3p inhibited ERK1/2 and Akt phosphorylation in LECs and LEC + MCF-7 spheroids, which are importantly involved in promoting cancer development and metastasis. Treatment of LECs and LEC + MCF-7 spheroids with estradiol (E2)-induced growth, as well as ERK1/2 and Akt phosphorylation, and was abrogated by miR193a-3p and secretome from MCF-7 transfected cells. Gene expression analysis (GEA) in LEC + MCF-7 spheroids transfected with miR193a-3p showed significant upregulation of 54 genes and downregulation of 73 genes. Pathway enrichment analysis of regulated genes showed significant modulation of several pathways, including interferon, interleukin/cytokine-mediated signaling, innate immune system, ERK1/2 cascade, apoptosis, and estrogen receptor signaling. Transcriptomic analysis showed downregulation in interferon and anti-apoptotic and pro-growth molecules, such as IFI6, IFIT1, OSA1/2, IFITM1, HLA-A/B, PSMB8/9, and PARP9, which are known to regulate BC progression. The cytokine proteome array of miR193a-3p transfected MCF secretome and confirmed the upregulation of several growth inhibitory cytokines, including IFNγ, Il-1a, IL-1ra, IL-32, IL-33, IL-24, IL-27, cystatin, C-reactive protein, Fas ligand, MIG, and sTIM3. Moreover, miR193a-3p alters factors in MCF-7 secretome, which represses ERK1/2 and Akt phosphorylation, induces pro-apoptotic protein and apoptosis in LECs, and downregulates interferon-associated proteins known to promote cancer growth and metastasis. In conclusion, miR193a-3p can potentially modify the tumor microenvironment by altering pro-growth BC secretome and inhibiting LEC growth, and may represent a therapeutic molecule to target breast tumors/cancer. [ABSTRACT FROM AUTHOR]

BACKGROUND Sexuality has a key impact on quality of life and on reproductive health. Infertility often results in sexual dysfunction. Despite this close association, addressing sexuality is not a standard component of infertility counselling, especially since in most countries sexual medicine is not a core element of specialist training. Even today, many doctors and patients consider discussing sexuality to be more challenging than other aspects of reproductive medicine. The present review addresses the complex consequences of infertility on sexuality. OBJECTIVE AND RATIONALE Our goals were: (i) to identify the prevalence of sexual problems resulting from infertility, (ii) to evaluate characteristics of sexual difficulties and disorders resulting from infertility and (iii) to analyse factors involved in the complex association between sexual problems and infertility. SEARCH METHODS A systematic search for publications containing keywords related to sexual disorders and infertility was performed via PubMed, Web of Science and Psyndex. A total of 170 manuscripts published between January 1966 and April 2021 were identified after verification of inclusion and exclusion criteria. The reference lists in these manuscripts were searched for further relevant literature. Studies were reviewed for quality-related methodological details. OUTCOMES Couples diagnosed with infertility have an increased risk of sexual disorders. Loss of sexual desire and erectile dysfunction are among the most frequent sexual disorders resulting from infertility. Currently available literature reflects only fragmentarily the complexity of the diverse interactions. Sexuality plays out against the backdrop of interactions among personal, cultural, infertility-related and sexuality-related factors. Considering this complexity, it is crucial to evaluate individual profiles as well as partnership interactions to avoid a negative impact of infertility on a couple's sexual life. WIDER IMPLICATIONS Identifying sexual disorders as relevant considerations in the context of infertility and exploring their impact during the entire course of diagnosis and treatment constitute an important contribution to comprehensively care for the couples concerned. Counselling should focus on preventing the onset and aggravation of sexual disorders. As sexuality represents a major component of quality of life and of partnership, such support may improve not only the current overall wellbeing but also the chances of a satisfactory long-term partnership and family life. [ABSTRACT FROM AUTHOR]

To better understand the physiological basis of obesity in women, we investigated whether obesity or menstrual cycle phase affects laboratory test-meal size or meal-stimulated plasma cholecystokinin (CCK) concentration. Women with healthy weight (body mass index [BMI] of 18.5-24.9 kg/m2, N = 16) or obesity (BMI 30-39.9 kg/m2, N = 20) were tested once in the late-follicular or peri-ovulatory phase (LF/PO) and once in the mid-luteal phase (ML). Meals of ham sandwiches were offered and blood was sampled. Menstrual cycle phases were verified with participants' reports of menses and measurements of progesterone and luteinizing hormone (LH) concentrations. Women with obesity ate significantly larger meals than women with healthy weight, (mean, 711 [95% CI, 402-1013] kJ, P = 0.001, during the LF/PO and 426 [105-734] kJ, P = 0.027, larger during the ML). Women with healthy weight ate smaller meals during LF/PO than ML (decrease, 510 [192-821 kJ], P = 0.008), but women with obesity did not (decrease, 226 [−87-542] kJ, P = 0.15). CCK concentrations 18 to 30 minutes after meal onset were lower in women with obesity than in women with healthy weight during LF/PO (3.6 [3.1-4.1] vs 6.1 [4.5-7.7] pmol/L; P = 0.004), but not during ML, with a significant interaction effect (1.8 [1.2-2.4] pmol/L, P = 0.048). Women with obesity consumed larger meals than women with healthy weight but displayed reduced meal-stimulated plasma CCK concentrations. These data are consistent with the hypothesis that a defect in CCK secretion compromises satiation in obese women and contributes to the development or maintenance of obesity. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) cell secretome in the tumor microenvironment (TME) facilitates neo-angiogenesis by promoting vascular endothelial cell (VEC) growth. Drugs that block BC cell growth or angiogenesis can restrict tumor growth and are of clinical relevance. Molecules that can target both BC cell and VEC growth as well as BC secretome may be more effective in treating BC. Since small non-coding microRNAs (miRs) regulate cell growth and miR193a-3p has onco-suppressor activity, we investigated whether miR193a-3p inhibits MCF-7-driven growth (proliferation, migration, capillary formation, signal transduction) of VECs. Using BC cells and VECs grown in monolayers or 3D spheroids and gene microarrays, we demonstrate that: pro-growth effects of MCF-7 and MDA-MB231 conditioned medium (CM) are lost in CM collected from MCF-7/MDA-MB231 cells pre-transfected with miR193a-3p (miR193a-CM). Moreover, miR193a-CM inhibited MAPK and Akt phosphorylation in VECs. In microarray gene expression studies, miR193a-CM upregulated 553 genes and downregulated 543 genes in VECs. Transcriptomic and pathway enrichment analysis of differentially regulated genes revealed downregulation of interferon-associated genes and pathways that induce angiogenesis and BC/tumor growth. An angiogenesis proteome array confirmed the downregulation of 20 pro-angiogenesis proteins by miR193a-CM in VECs. Additionally, in MCF-7 cells and VECs, estradiol (E2) downregulated miR193a-3p expression and induced growth. Ectopic expression of miR193a-3p abrogated the growth stimulatory effects of estradiol E2 and serum in MCF-7 cells and VECs, as well as in MCF-7 and MCF-7+VEC 3D spheroids. Immunostaining of MCF-7+VEC spheroid sections with ki67 showed miR193a-3p inhibits cell proliferation. Taken together, our findings provide first evidence that miR193a-3p abrogates MCF-7-driven growth of VECs by altering MCF-7 secretome and downregulating pro-growth interferon signals and proangiogenic proteins. Additionally, miR193a-3p inhibits serum and E2-induced growth of MCF-7, VECs, and MCF-7+VEC spheroids. In conclusion, miRNA193a-3p can potentially target/inhibit BC tumor angiogenesis via a dual mechanism: (1) altering proangiogenic BC secretome/TME and (2) inhibiting VEC growth. It may represent a therapeutic molecule to target breast tumor growth. [ABSTRACT FROM AUTHOR]

Vascular and lymphatic vessels drive breast cancer (BC) growth and metastasis. We assessed the cell growth (proliferation, migration, and capillary formation), gene-, and protein-expression profiles of Vascular Endothelial Cells (VECs) and Lymphatic Endothelial Cells (LECs) exposed to a conditioned medium (CM) from estrogen receptor-positive BC cells (MCF-7) in the presence or absence of Estradiol. We demonstrated that MCF-7-CM stimulated growth and capillary formation in VECs but inhibited LEC growth. Consistently, MCF-7-CM induced ERK1/2 and Akt phosphorylation in VECs and inhibited them in LECs. Gene expression analysis revealed that the LECs were overall (≈10-fold) more sensitive to MCF-7-CM exposure than VECs. Growth/angiogenesis and cell cycle pathways were upregulated in VECs but downregulated in LECs. An angiogenesis proteome array confirmed the upregulation of 23 pro-angiogenesis proteins in VECs. In LECs, the expression of genes related to ATP synthesis and the ATP content were reduced by MCF-7-CM, whereas MTHFD2 gene, involved in folate metabolism and immune evasion, was upregulated. The contrasting effect of MCF-7-CM on the growth of VECs and LECs was reversed by inhibiting the TGF-β signaling pathway. The effect of MCF-7-CM on VEC growth was also reversed by inhibiting the VEGF signaling pathway. In conclusion, BC secretome may facilitate cancer cell survival and tumor growth by simultaneously promoting vascular angiogenesis and inhibiting lymphatic growth. The differential effects of BC secretome on LECs and VECs may be of pathophysiological relevance in BC. [ABSTRACT FROM AUTHOR]

Background: Pain plays a central role in endometriosis. The complex relationship among pain characteristics, comorbid pain disorders and daily life represents a challenge for medical support. This multicentre cross‐sectional case–control study analysed the association between endometriosis‐related chronic pain and functions of daily life in 510 women with endometriosis, 265 (52%) who experienced chronic pain, either from endometriosis alone (N = 134, 26.3%) or in association with additional pain disorders (N = 131, 25.7%). Methods: Self‐administered questionnaires from the Brief Pain Inventory and the Pain Disability Index were used to investigate associations between pain characteristics (frequency, duration, intensity) and daily life. Also, associations between different endometriosis characteristics (rASRM stage, presence of adhesions, localisation of lesions) and pain were evaluated. Results: Chronic pain is negatively associated with almost all (12/14) aspects of daily life investigated, including standing, walking, sitting, defaecation, sleep, sports activities, family and domestic responsibilities, sexuality, social functioning, professional life, mood, and joy of life. Altogether, 33.7% of women with chronic pain reported moderate and 27.5% severe limitations. Comorbid pain disorders resulted in significantly more limitations. The length of pain episodes showed a particularly important influence, especially for family/domestic responsibilities (OR 22.94, p < 0.001), professional life (OR 16.56, p < 0.001) and social functioning (OR 41.03, p < 0.001). Conclusions: Our data confirm that despite treatment, about 50% of women experience pain. Pain was associated with at least moderate negative effects on almost all areas of daily life; additional pain comorbidities increased limitations. Improving pain management is essential for improving quality of life in women with endometriosis. Significance: The study provides an accurate overview of the impact of endometriosis‐associated pain on daily life. This is important because pain plays a central role in women living with endometriosis, and despite modern therapies, many women continue to suffer from chronic pain. The detailed analysis of its impact with a comprehensive survey of all aspects of daily life in a very large study population is unique. We expect an improved understanding of consequences of pain to significantly advance medical support in these patients. [ABSTRACT FROM AUTHOR]

Background: The importance of menstrual cycle physiology in appetite and obesity is poorly understood. We investigated the effects of body mass index (BMI), menstrual cycle phase and sweet and salty taste on monetary valuation of snack foods. Methods: We recruited 72 women and after the application of in- and exclusion criteria 31 participants with healthy weight and 25 with obesity remained. The participants completed a willingness to pay (WTP) task to measure subjective value of 30 snack food items in the pre-ovulatory and mid-luteal cycle phases. Results: Generalized linear mixed model (GLMM) analysis revealed that BMI, cycle phase and snack taste interacted to influence WTP (−0.15 [−0.22, −0.03], p = 0.002). Hence, WTP was inversely related to BMI, but the strength of the relation depended on cycle phase and taste. The WTP of participants with healthy weight for salty taste changed across cycle phase but the WTP for sweet taste was not affected by cycle phase. Moreover, the cycle effect for the salty snacks ceased in participants with obesity. Conclusion: The inverse effect of BMI on WTP valuation of snack foods contrasts with the positive effect of BMI on pleasantness ratings for milkshakes by the same women that we previously reported. This indicates that the two measures reflect different aspects of food-related valuative processing in obesity. Furthermore, the WTP data suggest that the selection of salty snacks may differ from that of sweet snacks in the pre-ovulatory phase of the menstrual cycle for individuals of healthy weight. The cycle phase does not seem to affect food valuation of participants with obesity. These findings are relevant to understanding and treating obesity in women. [ABSTRACT FROM AUTHOR]

Copyright of Gynäkologische Endokrinologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

New approaches to ovarian stimulation protocols, such as luteal start, random start or double stimulation, allow for flexibility in ovarian stimulation at different phases of the menstrual cycle. It has been proposed that the success of these methods is based on the continuous growth of multiple cohorts ("waves") of follicles throughout the menstrual cycle which leads to the availability of ovarian follicles for ovarian controlled stimulation at several time points. Though several preliminary studies have been published, their scientific evidence has not been considered as being strong enough to integrate these results into routine clinical practice. This work aims at adding further scientific evidence about the efficiency of variable-start protocols and underpinning the theory of follicular waves by using mathematical modeling and numerical simulations. For this purpose, we have modified and coupled two previously published models, one describing the time course of hormones and one describing competitive follicular growth in a normal menstrual cycle. The coupled model is used to test ovarian stimulation protocols in silico. Simulation results show the occurrence of follicles in a wave-like manner during a normal menstrual cycle and qualitatively predict the outcome of ovarian stimulation initiated at different time points of the menstrual cycle. [ABSTRACT FROM AUTHOR]

Introduction: Youths are particularly at risk of experiencing sexual victimization but research tends to focus on the most violent forms (i.e. rape or child sexual abuse) and on female cases. This study aimed at identifying factors associated to different types of unwanted sexual experiences (USE) among young females and males as well as estimating probabilities of experiencing sexual victimization among gender. Methods: Data were drawn from a cross-sectional survey on sexual health and behaviors using a nationally representative sample of youths aged 24–26 living in Switzerland. Respondents (N = 5290) were divided in three categories of reported USE, ordered by conceptualized severity. The fourth group was constituted of those never having experienced any. Weighted bivariate and multivariate analyses were performed using demographic characteristics and risk behavior indicators. Results: At the multivariate level, the higher the severity of USE, the higher the number of associated factors, revealing the complexity of this issue. Females had a higher probability of experiencing sexual victimization than of never experiencing any, with a probability of two out of three. They faced higher probabilities of sexual victimization than males, although males' probability of USE were not as marginal as expected, further considering that they are found to face higher rates of non-disclosure than females. Conclusion: USE is a complex issue, and the level of complexity increases in parallel with its severity. Although it is much more frequent among females, males report highers rates than expected. Policy implications: When investigating sexual victimization, there is a need to consider the diverse forms of USE and adopt a gendered approach in order to better comprehend sexual victimization and effectively intervene on the social, legal, and public health levels to prevent sexual victimization among youths. [ABSTRACT FROM AUTHOR]

In Silico Clinical Trials (ISCT), i.e. clinical experimental campaigns carried out by means of computer simulations, hold the promise to decrease time and cost for the safety and efficacy assessment of pharmacological treatments, reduce the need for animal and human testing, and enable precision medicine. In this paper we present methods and an algorithm that, by means of extensive computer simulation-based experimental campaigns (ISCT) guided by intelligent search, optimise a pharmacological treatment for an individual patient (precision medicine). We show the effectiveness of our approach on a case study involving a real pharmacological treatment, namely the downregulation phase of a complex clinical protocol for assisted reproduction in humans. [ABSTRACT FROM AUTHOR]

Background:One of the possible negative consequences of sexting is the non-consensual sharing of received-intimate content. This study aimed to determine the characteristics and motives of youths who shared received-intimate images without consent. Methods: Data were obtained from a self-administrated Swiss survey on sexual behaviours among young adults (aged 24-26 years). Out of the 7142 participants, 5175 responded to the question 'Have you ever shared (forwarding or showing) a sexy photograph/video of someone else (known or unknown) without consent'?; 85% had never shared (Never), 6% had shared once (Once) and 9% had shared several times (Several). Data are presented as relative risk ratios with 95% confidence intervals. Results: Participants who had shared received-intimate content without consent had higher odds of being male [2.73 (2.14-3.47)], foreign-born [1.45 (1.04-2.03)], reporting a non-heterosexual orientation [1.46 (1.10-1.93)], having sent one's own intimate image [1.76 (1.32-2.34)] and receiving a shared-intimate image of someone unknown [4.56 (3.28-6.36)] or known [2.76 (1.52-5.01)] compared with participants who had never shared. The main reported motivations were for fun (62%), showing off (30%) and failure to realise what they were doing (9%). Conclusions: Given the reported motivations, it appears crucial to remind youths of the seriousness of non-consensual sharing. Although females may also be perpetrators, the behaviour was more prevalent among males. Prevention and education need to consider a broad range of young people in their scenarios. Even if a particular focus on understanding and preventing males' perpetration must be considered, overall perpetration, including female's, must be discussed. [ABSTRACT FROM AUTHOR]

Background The aims of this research were to determine personal differences depending on the reason for regretting or not first vaginal intercourse and its effects on sexual behaviour later on among young adults, and to assess the association between reasons for engaging in first vaginal intercourse and regretting it.Methods: Data were drawn from the 2017 Swiss national survey on youth sexual behaviours among young adults (mean age 26 years) living in Switzerland. Out of the 7142 participants, 4793 (51% females) answered the question 'Looking back now to the first time you had vaginal intercourse, do you think that…' with five possible answers: (1) I should not have done it (6.7%); (2) I should have waited longer (7.7%); (3) I should have done it earlier (7.4%); (4) It was about the right time (67.9%); and (5) I don't know (10.3%). The five groups were compared on sociodemographic and sex behaviour-related variables, analysed separately by gender.Results: One-third of participants regretted their first experience. In the multivariate analysis, compared with the 'right time' group, all other groups were more likely to find their first experience unpleasant and to have done it with a casual partner. Those in the 'I should not have done it' and 'I should have waited longer' groups were also more likely to have done it because of external pressure, especially among females.Conclusions: The study results underline the significance to choose the right time and the right partner for first vaginal intercourse and the importance of including partner respect and avoiding external pressure as part of sexual education. [ABSTRACT FROM AUTHOR]

Sex education (SE) remains a subject of debate, including controversies on resources. The purpose of this paper was to determine the main SE resource during adolescence and its associations with personal characteristics and sexual behaviors of youths. Data were obtained from a self-administrated Swiss national survey on sexuality among young adults (mean age 26.3). Participants (N = 4978) were divided into six groups according to their main SE resource during their adolescence: Friends (1939; 38.9%), Parents (1361; 27.3%), School (n = 949; 19.1%), The Internet (399; 8.0%), Nobody (172; 3.5%) and Other (157; 3.2%). Groups were compared on sociodemographic, first sexual experiences, pregnancy, risky sexual behaviors, and undesired sexual experiences data. Males and non-heterosexual participants were overrepresented in the Internet group while, females more often reported their parents as their main SE resource. Participants in the School group reported the lowest rates of sexually transmitted infections and Friends the highest. Compared to the School group, those in the Friends, Internet, Nobody, and Other groups were more likely to report undesired sexual experiences. Few differences appeared between parents and school. Even though some resources such as friends or the Internet presented negative outcomes when they were assessed individually, we cannot deny the important place that they occupy in the lives of some youths. [ABSTRACT FROM AUTHOR]

Stress is a risk factor for impaired general, mental, and reproductive health. The role of physiological and supraphysiological estradiol concentrations in stress perception and stress processing is less well understood. We, therefore, conducted a prospective observational study to investigate the association between estradiol, stress perception, and stress-related cognitive performance within serial measurements either during the natural menstrual cycle or during fertility treatment, where estradiol levels are strongly above the physiological level of a natural cycle, and consequently, represent a good model to study dose-dependent effects of estradiol. Data from 44 women receiving in vitro fertilization (IVF) at the Department of Reproductive Endocrinology in Zurich, Switzerland was compared to data from 88 women with measurements during their natural menstrual cycle. The German version of the Perceived Stress Questionnaire (PSQ) and the Cognitive Bias Test (CBT), in which cognitive performance is tested under time stress were used to evaluate subjective and functional aspects of stress. Estradiol levels were investigated at four different time points during the menstrual cycle and at two different time points during a fertility treatment. Cycle phases were associated with PSQ worry and cognitive bias in normally cycling women, but different phases of fertility treatment were not associated with subjectively perceived stress and stress-related cognitive bias. PSQ lack of joy and PSQ demands related to CBT in women receiving fertility treatment but not in women with a normal menstrual cycle. Only strong changes of the estradiol level during fertility treatment were weakly associated with CBT, but not with subjectively experienced stress. Our research emphasizes the multidimensional character of stress and the necessity to adjust stress research to the complex nature of stress perception and processing. Infertility is associated with an increased psychological burden in patients. However, not all phases of the process to overcome infertility do significantly increase patient stress levels. Also, research on the psychological burden of infertility should consider that stress may vary during the different phases of fertility treatment. Clinical trial registration: ClinicalTrials.gov # NCT02098668. [ABSTRACT FROM AUTHOR]

Objectives Endometriosis is a gynaecological disease most commonly causing severe and chronic pelvic pain as well as an impaired quality of life. The aim of this study was to investigate if and how endometriosis affects choices regarding professional life as well as the quality of daily working life. Design, setting and participants In the context of a multicentre case-control study, we collected data from 505 women with surgically/histologically confirmed diagnosis of endometriosis and 505 matched controls. Study participants were recruited prospectively in hospitals and doctors' practices in Switzerland, Germany and Austria. Using a detailed questionnaire, the study investigated work-life and career choices of study participants. Main outcome measures Associations between endometriosis/disease symptoms and limitations in career development as well as ability to work. Results Women with endometriosis were less often able to work in their desired profession than women from the control group (adjusted OR=1.84, 95% CI: 1.15 to 2.94, R²=0.029, p=0.001) and they had to take health-related limitations into consideration in their career decisions to a significantly higher degree than women in the control group (OR=4.79, 95% CI: 2.30 to 9.96, R²=0.063, p<0.001). Among women with endometriosis, chronic pain was significantly associated with increased sick leave (OR=3.52, 95% CI: 2.02 to 6.13, R²=0.072, p<0.001) as well as with loss of productivity at work (OR=3.08, 95% CI: 2.11 to 4.50, R²=0.087, p<0.001). Conclusions Endometriosis is associated with impairment of professional life, in particular with regard to career choices. Further research to develop strategies to support endometriosis-affected women in realising professional opportunities is recommended. [ABSTRACT FROM AUTHOR]

Objectives: The aims of the study were to conduct an analysis of intrauterine device (IUD)-related outcomes, including continuation rates, reasons for discontinuation, rates of dislocation and risk factors for dislocation, in a clinical setting with regular ultrasound monitoring of the IUD position.Methods: A retrospective chart review was carried out of all IUD insertions over a period of 5 years.Results: A total of 755 IUDs were inserted over the study period. The overall observation time was 1572 woman-years. The removal rate was highest in the first year after insertion and did not differ between devices: the 52 mg levonorgestrel-releasing intrauterine system (LNG-IUS; 18%) and third generation copper-T (Cu-T) IUDs (20%). Most removals were related to dislocation; fewer dislocations were seen with the LNG-IUS compared with the Cu-T IUDs (p< .001). More removals of the LNG-IUS were carried out because of amenorrhoea, pain and hormone-related adverse events (20% of all removals). The discontinuation rate was higher in young women (age <25 years; p< .03), demonstrating the limitations of long-acting reversible contraception in this age group. The dislocation rate for devices replaced after dislocation was 31% in women receiving a Cu-T IUD and 38% in women receiving an LNG-IUS.Conclusions: The first year after IUD insertion is crucial with regard to discontinuation. Most removals were attributed to dislocation and affected mainly younger women. Dislocations occurred more rarely in LNG-IUS users and the rate decreased over time. We recommend follow-up within the first 6-12 months, especially in young women. Structured counselling and consideration of risk factors for dislocation may reduce removal rates for adverse events and dislocations. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Circadian and circannual rhythms influence not only the environment, but also human physiology. In times of increasing numbers of couples struggling with infertility, and thus increasing demand for successful assisted reproduction, the aim of our study was to evaluate circadian and circannual rhythms and their association with semen quality. A total of 12 245 semen samples from 7068 men, collected at the andrology laboratory of the Department of Reproductive Endocrinology, University Hospital Zurich, between 1994 and 2015, were uniformly analysed in terms of sperm concentration, total sperm count, progressive motility and normal morphology. On the basis of these four parameters, we retrospectively examined the circadian and circannual changes of semen quality. The Mann-Whitney U test and multiple linear regression analysis were used for the statistical evaluation. The semen samples collected in the early morning before 7:30 a.m. showed the highest levels in sperm concentration, total sperm count and normal morphology, all with statistical significance. Progressive motility did not show any significant alterations based on circadian rhythm. Furthermore, a significant increase in sperm concentration and total sperm count was found in spring, with significant decreases in the summer. The highest percentage of normal morphology was found in summer. For progressive motility, no significant seasonal variation could be demonstrated. Male semen quality varies with both circadian and circannual rhythms. Collection of semen in the early morning, where semen quality was highest, can be used to improve natural fertility as well as fertility resulting from assisted reproduction. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: It is not uncommon for women with endometriosis to be advised that becoming pregnant might be a useful strategy to manage their symptoms and reduce disease progression. Consequently, many women diagnosed with endometriosis and motivated to become pregnant, may also have expectations regarding improvement of symptoms and the disease. However, study results on the effect of pregnancy on endometriosis are controversial and pregnancy in women with endometriosis is not always associated with improved symptoms. Moreover, there is increasing evidence that endometriosis may interfere with a successful pregnancy outcome.Objective and Rationale: The objective was to evaluate the evidence on whether pregnancy and lactation has a beneficiary effect on growth characteristics and symptoms of endometriosis diagnosed prior to pregnancy.Search Methods: A search for articles containing keywords related to pregnancy and endometriosis was performed via PubMed. Manuscripts dealing with a potential effect of pregnancy on endometriosis were systematically reviewed. We included English, French and German language publications on human studies from 1966 to May 2017. Bibliographies of these manuscripts were searched for further relevant literature.Outcomes: Five small observational studies were identified concerning the longitudinal development of endometriotic lesions during and after pregnancy, four of medium and one of low quality. Eleven publications reported measurements of endometriomas during pregnancy and the postpartum period (the five studies just mentioned and six case reports). Another 22 case reports/small case series (maximum of five cases), six studies on histology of endometriotic lesions in pregnancy, plus eight studies on the role of pregnancy in initial development and recurrence of endometriosis were included. Few studies of very limited quality are available to evaluate the effect of pregnancy and the postnatal period on the development of endometriosis. The development of endometriosis is variable and there is no evidence that pregnancy can be expected to generally reduce the size and number of endometriotic lesions. Growth and structural changes of lesions during pregnancy may occur with decidualization. Results on the association between pregnancy and symptoms of endometriosis are controversial and strongly biased.Wider Implications: Available data on the development of endometriosis during and after pregnancy show fewer beneficial effects than previously reported. Therefore, women aiming for pregnancy on the background of endometriosis should not be told that pregnancy may be a strategy for managing symptoms and reducing progression of the disease. [ABSTRACT FROM AUTHOR]

Human and animal data indicate that the dopaminergic system plays a crucial role in sexual drive and function. Using a double-blind, placebo-controlled crossover design, this prototype study investigated the effect of the D2 dopamine agonist cabergoline on sexual parameters in 13 healthy women. Cardiovascular and genital parameters were monitored continuously. Sexual drive and function were measured using self-report sexual experience scales. In contrast to previous theories and assumptions, we found that cabergoline did not alter objective and subjective sexual parameters in healthy women. This finding suggests that there may be sex differences in the influence of the dopaminergic system on human sexual functioning. [ABSTRACT FROM AUTHOR]

We previously reported that piperine, an active alkaloidal principal of black and long peppers, enhances drug bioavailability by inhibiting drug metabolism. Another mechanism influencing drug availability/uptake is its free fraction. Since piperine is highly lipophilic, we hypothesize that it could also interact with drugs through binding displacement and influence their bioavailability. Accordingly, using equilibrium dialysis, we investigated whether piperine alters the binding of model drug ligands, that is flunitrazepam, diazepam, warfarin, salicylic acid, propranolol, lidocaine, and disopyramide to human plasma (n = 4). Since alterations in binding influence drug disposition, we also studied the effects of piperine on the uptake of plasma bound 3 H-propranolol and 14 C-warfarin by cultured bovine brain microvascular endothelial cells (BMECs). Piperine (1-1000 μM) increased the free fraction (fu) of both albumin and alpha-acid glycoprotein bound drugs in a concentration-dependent manner (p < 0.01). Moreover, piperine (10 μM) increased the uptake of 3 H-propranolol and 14 C-warfarin by BMECs (p < 0.01). In conclusion, our findings provide the first evidence that piperine displaces plasma bound drugs from both albumin and alpha-acid glycoprotein and facilitates drug uptake across biological membranes (e.g. BMEC). Moreover, it is feasible that piperine may similarly facilitate the transport of drugs into tissues, in vivo, and alter both pharmacokinetics and pharmacodynamics of administered drugs. Copyright © 2017 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background: Interpretation of observational studies on associations between prefrontal cognitive functioning and hormone levels across the female menstrual cycle is complicated due to small sample sizes and poor replicability. Methods: This observational multisite study comprised data of n = 88 menstruating women from Hannover, Germany, and Zurich, Switzerland, assessed during a first cycle and n = 68 re-assessed during a second cycle to rule out practice effects and false-positive chance findings. We assessed visuospatial working memory, attention, cognitive bias and hormone levels at four consecutive time-points across both cycles. In addition to inter-individual differences we examined intra-individual change over time (i.e., within-subject effects). Results: Estrogen, progesterone and testosterone did not relate to inter-individual differences in cognitive functioning. There was a significant negative association between intra-individual change in progesterone and change in working memory from pre-ovulatory to mid-luteal phase during the first cycle, but that association did not replicate in the second cycle. Intra-individual change in testosterone related negatively to change in cognitive bias from menstrual to pre-ovulatory as well as from pre-ovulatory to mid-luteal phase in the first cycle, but these associations did not replicate in the second cycle. Conclusions: There is no consistent association between women's hormone levels, in particular estrogen and progesterone, and attention, working memory and cognitive bias. That is, anecdotal findings observed during the first cycle did not replicate in the second cycle, suggesting that these are false-positives attributable to random variation and systematic biases such as practice effects. Due to methodological limitations, positive findings in the published literature must be interpreted with reservation. [ABSTRACT FROM AUTHOR]

Background: Obesity is caused by an imbalance between energy intake, i.e. eating and energy expenditure (EE). Severe obesity is more prevalent in women than men worldwide, and obesity pathophysiology and the resultant obesity-related disease risks differ in women and men. The underlying mechanisms are largely unknown. Pre-clinical and clinical research indicate that ovarian hormones may play a major role.Objective and Rationale: We systematically reviewed the clinical and pre-clinical literature on the effects of ovarian hormones on the physiology of adipose tissue (AT) and the regulation of AT mass by energy intake and EE.Search Methods: Articles in English indexed in PubMed through January 2016 were searched using keywords related to: (i) reproductive hormones, (ii) weight regulation and (iii) central nervous system. We sought to identify emerging research foci with clinical translational potential rather than to provide a comprehensive review.Outcomes: We find that estrogens play a leading role in the causes and consequences of female obesity. With respect to adiposity, estrogens synergize with AT genes to increase gluteofemoral subcutaneous AT mass and decrease central AT mass in reproductive-age women, which leads to protective cardiometabolic effects. Loss of estrogens after menopause, independent of aging, increases total AT mass and decreases lean body mass, so that there is little net effect on body weight. Menopause also partially reverses women's protective AT distribution. These effects can be counteracted by estrogen treatment. With respect to eating, increasing estrogen levels progressively decrease eating during the follicular and peri-ovulatory phases of the menstrual cycle. Progestin levels are associated with eating during the luteal phase, but there does not appear to be a causal relationship. Progestins may increase binge eating and eating stimulated by negative emotional states during the luteal phase. Pre-clinical research indicates that one mechanism for the pre-ovulatory decrease in eating is a central action of estrogens to increase the satiating potency of the gastrointestinal hormone cholecystokinin. Another mechanism involves a decrease in the preference for sweet foods during the follicular phase. Genetic defects in brain α-melanocycte-stimulating hormone-melanocortin receptor (melanocortin 4 receptor, MC4R) signaling lead to a syndrome of overeating and obesity that is particularly pronounced in women and in female animals. The syndrome appears around puberty in mice with genetic deletions of MC4R, suggesting a role of ovarian hormones. Emerging functional brain-imaging data indicates that fluctuations in ovarian hormones affect eating by influencing striatal dopaminergic processing of flavor hedonics and lateral prefrontal cortex processing of cognitive inhibitory controls of eating. There is a dearth of research on the neuroendocrine control of eating after menopause. There is also comparatively little research on the effects of ovarian hormones on EE, although changes in ovarian hormone levels during the menstrual cycle do affect resting EE.Wider Implications: The markedly greater obesity burden in women makes understanding the diverse effects of ovarian hormones on eating, EE and body adiposity urgent research challenges. A variety of research modalities can be used to investigate these effects in women, and most of the mechanisms reviewed are accessible in animal models. Therefore, human and translational research on the roles of ovarian hormones in women's obesity and its causes should be intensified to gain further mechanistic insights that may ultimately be translated into novel anti-obesity therapies and thereby improve women's health. [ABSTRACT FROM AUTHOR]

Copyright of European Journal of Contraception & Reproductive Health Care is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Childhood sexual abuse (CSA) can have a serious effect on general and obstetric health. Breastfeeding includes several triggers for memories of abuse experiences, which will likely influence decisions about breastfeeding and its implementation in daily life. This is important since breastfeeding improves maternal well-being and bonding with the child. Research aim: As breastfeeding strongly influences the long-term health of children, we investigated experiences with breastfeeding in women with a history of CSA. Methods: Data on breastfeeding were collected within a research project designed to compare labor and delivery experiences in women with a history of CSA to women without such antecedents. Data from 85 women having experienced CSA and 170 controls pair-matched for maternal age, children’s age, and nationality were evaluated. The clinical record of pregnancy and a self-administered questionnaire were used to collect data. Results: Although the prevalence of breastfeeding was similar in women with and without CSA experiences (96.5% vs. 90.6%), women exposed to CSA more often described complications associated with breastfeeding (77.7% vs. 67.1%, p = .08). Mastitis (49.4% vs. 27.6%, p < .01) and pain (29.4% vs. 18.8%, p = .15) were reported significantly more often by women after CSA. For 20% of women after CSA, breastfeeding was a trigger for memories of CSA. Furthermore, 58% of women with CSA reported dissociation when breastfeeding. Conclusion: In addition to the growing list of potential health consequences of CSA experience, this experience seems to be associated with an increased number of problems when breastfeeding. However, most women with a history of CSA intend to breastfeed despite particular challenges related to CSA. A support protocol tailored to the specific needs of these women during pregnancy and the lactation period may help to improve breastfeeding and the early mother–child relationship. [ABSTRACT FROM AUTHOR]

Copyright of Der Gynäkologe is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Gynecological Endocrinology is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)