Ludwig Kiesel

University of Münster | WWU · Clinic for Obstetrics and Gynecology

Introduction Adenomyosis is a special subtype of endometriosis, affecting the myometrium, affecting about 20% of women in the reproductive age period. Clinical symptoms and intensity are diverse and can vary from heavy menstrual bleeding and dysmenorrhea to infertility and repeated pregnancy losses. Thus, patients often present with a long history...

Ferroptosis, an iron-dependent form of non-apoptotic cell death, plays a pivotal role in various diseases and is gaining considerable attention in the realm of endometriosis. Considering the classical pathomechanism theories, we hypothesized that ferroptosis, potentially driven by increased iron content at ectopic sites, may contribute to the progr...

Objective The aim of the study is to identify appropriate definitions and patient-reported outcome measures (PROMs) for each of the eight core outcomes previously selected for genitourinary symptoms associated with menopause: pain with sex, vulvovaginal dryness, vulvovaginal discomfort or irritation, discomfort or pain when urinating, change in mos...

Objective The aim of the study is to identify suitable definitions and patient-reported outcome measures (PROMs) to assess each of the six core outcomes previously identified through the COMMA (Core Outcomes in Menopause) global consensus process relating to vasomotor symptoms: frequency, severity, distress/bother/interference, impact on sleep, sat...

Endometriosis is a chronic condition affecting reproductive-aged women, characterized by the growth of ectopic endometrial tissue. Despite being benign, endometriosis is associated with an increased risk of certain cancers, including endometriosis-associated ovarian cancer (EAOC). Ovarian cancer is rare, but more common in women with endometriosis,...

Introduction Bisphenol A is a synthetic compound widely used in the production of polycarbonate plastics and epoxy resins worldwide. As an environmental toxin, it has been reported in plastic equipment and utensils, water bottles and bottle tops, water supply pipes and epoxy resins that coat most of the metal food cans. It is a known endocrine-disr...

The S3-guideline on endometrial cancer, first published in April 2018, was reviewed in its entirety between April 2020 and January 2022 and updated. The review was carried out at the request of German Cancer Aid as part of the Oncology Guidelines Program and the lead coordinators were the German Society for Gynecology and Obstetrics (DGGG), the Gyn...

The S3-guideline on endometrial cancer, first published in April 2018, was reviewed in its entirety between April 2020 and January 2022 and updated. The review was carried out at the request of German Cancer Aid as part of the Oncology Guidelines Program and the lead coordinators were the German Society for Gynecology and Obstetrics (DGGG), the Gyn...

By causing chronic systemic inflammation, oxidative stress, and other factors that, among others, affect the immune system, endometriosis can influence the pathogenesis of many other diseases. Since endometriosis affects approximately 10% of women, it is important to know the systemic effects and comorbidities of the disease in order to prevent seq...

Simple Summary Ovarian cancer has high prevalence and mortality in women. An early diagnosis of cancer is associated with a better prognosis of the oncologic patients. Ovarian cancer generally presents non-specific symptoms, and thus is frequently diagnosed only when the patients have an advance stage of the disease, resulting in higher mortality....

Purpose MicroRNA-218 (miR-218) is a key regulator of numerous processes relevant to tumor progression. In the present study, we aimed to characterize the relationship between miR-218 and the Epidermal Growth Factor Receptor (EGFR) as well as to understand downstream effects in triple-negative breast cancer (TNBC). Methods We assessed miR-218 and E...

Background: Women in the peri- or postmenopause can experience symptoms related to the gradual degradation of ovarian function. Hormone replacement therapy (HRT) is the most effective therapy to treat common menopausal symptoms such as hot flashes and vaginal discomfort. However, safety concerns have been raised revolving, among others also, aroun...

Objective: Progesterone metabolites 5α-dihydroprogesterone (5αP) and 3α-dihydroprogesterone (3αP) have opposite effects on proliferation, apoptosis and metastasis in the breast. Evidence regarding their influence on ductal carcinoma in situ (DCIS) lesions is lacking. Methods: MCF10DCIS.com cells were cultured in a 3D culture system and treated w...

Introduction: In breast cancer patients, menopausal symptoms are often reached earlier and in a more severe manner than in healthy women. They can dramatically reduce a patient's quality of life. Treatment for breast cancer patients remains difficult due to hormone replacement therapy being contraindicated. Therefore, treatment alternatives like h...

Background Ductal carcinoma in situ (DCIS) is a precursor form of breast cancer. 13%–50% of these lesions will progress to invasive breast cancer, but the individual progression risk cannot be estimated. Therefore, all patients receive the same therapy, resulting in potential overtreatment of a large proportion of patients. Aims The role of the tu...

Training and education in diagnosis and therapy of endometriosis.

Background: Polycystic ovary syndrome (PCOS) is the most common cause of infrequent periods (oligomenorrhoea) and absence of periods (amenorrhoea). It affects about 5% to 20% of women worldwide and often leads to anovulatory infertility. Aromatase inhibitors (AIs) are a class of drugs that were introduced for ovulation induction in 2001. Since abo...

Due to demographic change and the resultant increase in the number of years women spend postmenopausal, there is an increasing demand for good treatment options for GSM (genitourinary syndrome of the menopause). Especially for patients for whom hormonal therapy is not an option for medical or personal reasons, vaginal CO2 (carbon dioxide) laser the...

Study question Do Musashi proteins mechanistically contribute to the pathogenetic properties of endometriotic cells? Summary answer Silencing of Musashi-1 and Muashi-2 reduces the expression of stemness-related genes, inhibits spheroid growth and viability, and increases apoptosis in endometriotic cells. What is known already Putative stem cells...

In 2005, under the auspices of ESHRE, a group of international experts evaluated the existing best evidence and published the first European guideline on the management of endometriosis. This highly successful project was the first guideline by ESHRE and was adopted by many counties as their national standard. A second, fully-updated edition was pr...

Purpose Hyaluronan modulates tumour progression, including cell adhesion, cohesion, proliferation and invasion, and the cancer stem cell phenotype. In ovarian cancer, high levels of stromal hyaluronan are associated with poor prognosis. In this work, hyaluronan synthases (HAS1-3) and hyaluronidases (HYAL1-4, PH-20, HYALP1) were examined with regard...

Research has shown that endometriosis is an estrogen-dependent disease. Dysregulation of steroid action appears to be one of the key pathogenetic factors in altered cellular function in the endometrium as well as in lesions in women suffering from endometriosis. The normal hormonal balance and homeostasis are disturbed, leading to an increased estr...

Syndecans are transmembrane heparan sulfate proteoglycans that integrate signaling at the cell surface. By interacting with cytokines, signaling receptors, proteases, and extracellular matrix proteins, syndecans regulate cell proliferation, metastasis, angiogenesis, and inflammation. We analyzed public gene expression datasets to evaluate the dysre...

Ductal carcinoma in situ (DCIS) is a form of breast cancer that is restricted to the lactiferous ducts and has not yet invaded the surrounding breast tissue. Dysregulation of the transmembrane heparan sulphate proteoglycan Syndecan‐1 (Sdc‐1) plays a role in tumour progression of invasive breast cancer (IBC). In DCIS, Sdc‐1, c‐Met and E‐cadherin are...

The stem cell marker and RNA-binding protein Musashi-1 is overexpressed in endometriosis. Musashi-1-siRNA knockdown in Ishikawa cells altered the expression of stem cell related genes, such as OCT-4. To investigate the role of both human Musashi homologues (MSI-1 and MSI-2) in the pathogenesis of endometriosis, immortalized endometriotic 12-Z cells...

Study question: How should endometriosis be diagnosed and managed based on the best available evidence from published literature? Summary answer: The current guideline provides 109 recommendations on diagnosis, treatments for pain and infertility, management of disease recurrence, asymptomatic or extrapelvic disease, endometriosis in adolescents...

Aim This update of the interdisciplinary S3 guideline on the Diagnosis, Therapy and Follow-up of Cervical Cancer (AWMF Registry No. 032/033OL) was published in March 2021. This updated guideline was funded by German Cancer Aid (Deutsche Krebshilfe) as part of the German Guideline Program in Oncology. The guideline was coordinated by the German Soci...

Aim This is an update of the interdisciplinary S3-guideline on the Diagnosis, Therapy and Follow-up of Cervical Cancer (AWMF Registry No. 032/033OL), published in March 2021. The work on the updated guideline was funded by German Cancer Aid (Deutsche Krebshilfe) as part of the German Guideline Program in Oncology. The guideline was coordinated by t...

Research question Does resveratrol exert a potent inhibitory effect on the development of endometriosis by interfering over some pivotal processes? Design In vitro cultures of primary endometriotic stromal cells, immortalized endometrial stromal (St-T1b) and endometriotic epithelial (12Z) cells were utilized to assess the effects of resveratrol on...

Cervical cancer ranks fourth among the most commonly diagnosed malignant tumors in women worldwide. Previously published evidence suggested a possible connection between the expression of the membrane-bound heparan sulfate proteoglycan syndecan-1 (Sdc-1) and the development of cervical carcinoma. Sdc-1 serves as a matrix receptor and coreceptor for...

Purpose: Hyaluronan modulates tumor progression, including cell adhesion, cohesion, proliferation and invasion, and the cancer stem cell phenotype. In ovarian cancer, high levels of stromal hyaluronan are associated with poor prognosis. In this work hyaluronan synthases (HAS1-3) and hyaluronidases (HYAL1-5, HYALP1) were examined with regard to diff...

Purpose While the stem cell marker Musashi-1 (MSI-1) has been identified as a key player in a wide array of malignancies, few findings exist on its prognostic relevance and relevance for cancer cell death and therapy resistance in breast cancer. Methods First, we determined prognostic relevance of MSI-1 in database analyses regarding multiple surv...

Melanoma is one of the most common cancers in adolescents and adults at fertile age, especially in women. With novel and more effective systemic therapies that began to profoundly change the dismal outcome of melanoma by prolonging overall survival, the wish for fertility preservation or even parenthood has to be considered for a growing portion of...

PurposeDuctal carcinoma in situ (DCIS) is a preform of breast cancer. 13-50% of these lesions will progress to invasive breast cancer (IBC), but the individual progression risk cannot be estimated. Therefore, all patients receive the same therapy, resulting in potential overtreatment of a large proportion of patients. The role of the tumor microenv...

Introduction Worldwide, there are 657 million women aged 45–59 and around half contribute to the labor force during their menopausal years. There is a diversity of experience of menopause in the workplace. It is shaped not only by menopausal symptoms and context but also by the workplace environment. It affects quality of life, engagement, performa...

Aim The aim of the interdisciplinary S3-guideline Perimenopause and Postmenopause – Diagnosis and Interventions is to provide help to physicians as they inform women about the physiological changes which occur at this stage of life and the treatment options. The guideline should serve as a basis for decisions taken during routine medical care. This...

Syndecan-4, a predicted target of the microRNA miR-140-3p, plays an important role in multiple steps of tumor progression and is the second most abundant heparan sulfate proteoglycan produced by breast carcinoma cell lines. To investigate the potential functional relationship of miR-140-3p and syndecan-4, MDA-MB-231, SKBR3, and MCF-7 breast cancer...

Triple-negative breast cancer (TNBC) is characterized by increased angiogenesis, metastasis, and poor survival. Dysregulation of the cell surface heparan sulfate proteoglycan and signaling co-receptor Syndecan-1 is linked to poor prognosis. To study its role in angiogenesis, we silenced Syndecan-1 in TNBC cell lines using a 3D human umbilical vein...

Objective: Genitourinary symptoms, such as vaginal dryness and pain with sex, are commonly experienced by postmenopausal women. Comparing treatments for these genitourinary symptoms are restricted by the use of different outcome measures in clinical trials and the omission of outcomes, which may be relevant to women. The aim of this project was to...

Rapid advances in oncology have led to an increased survival rate in cancer patients, who live long enough to reach the natural age of menopause or experience the end of gonadal function as a side effect of oncological treatment. Survivors after gynaecological malignancies are a major challenge as these diseases are hormone-dependent and hormone re...

Objective: Vasomotor symptoms (VMS) (hot flashes and night sweats) affect most women over the menopause transition. Comparing the safety and effectiveness of treatments for vasomotor symptoms is limited by the use of inconsistent outcome measures, and uncertainty as to which outcomes are most important to symptomatic women. To address this, we hav...

Introduction Vulvovaginal atrophy (VVA) is a chronic condition caused by estrogen deficiency. It affects around 50% of postmenopausal women, reducing their general and sexual quality of life as well as the quality of their personal relationships. Aim The aim of this clinical guide is to set out an individualized approach to the management of VVA w...

STUDY QUESTION What are the effects of plant-derived antioxidant compounds urolithin A (UA) and B (UB) on the growth and pathogenetic properties of an in vitro endometriosis model? SUMMARY ANSWER Both urolithins showed inhibitory effects on cell behavior related to the development of endometriosis by differentially affecting growth, adhesion, moti...

Purpose: The aim of the study was to assess the impact of endometriosis on subsequent pregnancy and delivery. Methods: retrospective analysis by questionnaire / interview of cases (endometriosis laparoscopically removed / child wish) vs. controls (endometriosis laparoscopically excluded / child wish) from the University Hospital Muenster, Germany,...

Endometriosis is a painful gynecological condition characterized by ectopic growth of endometrial cells. Little is known about its pathogenesis, which is partially due to a lack of suitable experimental models. Here, we use endometrial stromal (St-T1b), primary endometriotic stromal, epithelial endometriotic (12Z) and co-culture (1:1 St-T1b:12Z) sp...

Aims This is an official interdisciplinary guideline published and coordinated by the German Society for Gynecology and Obstetrics (DGGG), the Austrian Society for Gynecology and Obstetrics (OEGGG) and the Swiss Society for Gynecology and Obstetrics (SGGG). The guideline was developed for use in German-speaking regions and is backed by numerous pro...

Breast cancer continues to be a serious public health problem. The role of the hedgehog pathway in normal development of the mammary gland as well as in carcinogenesis and progression of breast cancer is the subject of intense investigation, revealing functional interactions with cell surface heparan sulfate. Nevertheless, its influence on breast c...

Simple Summary Endometrial cancer is the most frequent gynecologic tumor in developed countries. Obesity is an established risk factor for this disease. This work provides an overview of pathophysiological interactions and pathways in obese women initiating tumorigenesis. Furthermore, the clinical impact of adiposity on the treatment of endometrial...

Background Polycystic ovary syndrome (PCOS) is the most common cause of infrequent periods (oligomenorrhoea) and absence of periods (amenorrhoea), often leading to subfertlity. The aim of this meta-analysis was to compare the effectiveness and safety of aromatase inhibitors with other medical therapies for ovulation induction in subfertile women wi...

Introduction: The prevalence of urinary incontinence and of other lower urinary tract symptoms increases after the menopause and affects between 38 % and 55 % of women aged over 60 years. While urinary incontinence has a profound impact on quality of life, few affected women seek care. Aim: The aim of this clinical guide is to provide an evidenc...

Heparan sulfate (HS) is a glycosaminoglycan found mainly in its protein-conjugated form at the cell surface and the extracellular matrix. Its high sulfation degree mediates functional interactions with positively charged amino acids in proteins. 2-O sulfation of iduronic acid and 3-O sulfation of glucosamine in HS are mediated by the sulfotransfera...

In women with endometriosis wishing to conceive, therapeutic strategies can differ significantly from those applied in patients suffering from endometriosis-associated pain. In the case of infertility, endocrine therapy is not an option. The resection of endometriosis needs to be carefully indicated since follicular reserve can be at risk due to th...

Downregulated microRNA-142-3p signaling contributes to the pathogenesis of endometriosis, an invasive disease where the lining of the uterus grows at ectopic locations, by yet incompletely understood mechanisms. Using bioinformatics and in vitro assays, this study identifies cytoskeletal regulation and integrin signaling as two relevant categories...

Downregulated microRNA-142-3p signaling contributes to the pathogenesis of endometriosis [1] [2], an invasive disease where the lining of the uterus grows at ectopic locations, by yet incompletely understood mechanisms. Using bioinformatics and in vitro assays, this study identifies cytoskeletal regulation and integrin signaling as two relevant cat...

Heparan sulfate proteoglycans (HSPGs) act as signaling coreceptors by interactions of their sulfated glycosaminoglycan chains with numerous signaling molecules. In breast cancer, the function of heparan sulfate 2‐O‐sulfotransferase (HS2ST1 ), the enzyme mediating 2‐O‐sulfation of HS, is largely unknown. Hence, a comparative study on the functional...

Introduction Globally, 985 million women are aged 50 and over, leading to increasing concerns about chronic conditions such as cardiovascular disease, osteoporosis, dementia, and cognitive decline, which can adversely affect quality of life and independent living. Aim To evaluate the evidence from observational studies and randomized trials on the...

Endometriosis is a painful gynaecological condition characterized by ectopic growth of endometrial cells outside of the uterus. Little is known about the mechanisms by which endometrial fragments invade tissues. This is partially due to a lack of suitable experimental models. In this study, we show that a spheroid 3D model, but not single cells mim...

Background State-of-the art therapy for recurrent ovarian cancer suitable for platinum-based re-treatment includes bevacizumab-containing combinations (eg, bevacizumab combined with carboplatin–paclitaxel or carboplatin–gemcitabine) or the most active non-bevacizumab regimen: carboplatin–pegylated liposomal doxorubicin. The aim of this head-to-head...

The therapeutic potential of Musashi (MSI) RNA-binding proteins, important stemness-associated gene expression regulators, remains insufficiently understood in breast cancer. This study identifies the interplay between MSI protein expression, stem cell characteristics, radioresistance, cell invasiveness and migration. MSI-1, MSI-2 and Notch pathway...