Search Results (500)

This article presents a narrative review that explores the potential link between kisspeptin—a key regulator of the hypothalamic-pituitary-gonadal axis—and the pathogenesis of endometriosis. Kisspeptin plays a significant role in regulating reproductive functions by modulating the release of gonadotropin-releasing hormone (GnRH), which in turn stimulates the secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Recent studies suggest that kisspeptin may also impact peripheral reproductive tissues and influence inflammatory processes involved in the development of endometriosis. Altered kisspeptin signaling has been associated with the abnormal hormonal environment observed in endometriosis, which affects menstrual cycles and ovarian function. Research indicates that women with endometriosis exhibit altered levels of kisspeptin and its receptor, KISS1R, in both eutopic and ectopic endometrial tissues, suggesting a role in disease progression, particularly in tissue invasion and lesion formation. Kisspeptin’s role in regulating matrix metalloproteinases (MMPs), enzymes essential for tissue remodeling, further supports its potential contribution to the pathophysiology of endometriosis. Moreover, kisspeptin-based therapeutic strategies are currently under investigation, with the aim of providing targeted treatments that reduce the side effects commonly associated with existing therapies. Despite promising findings, further research is needed to fully understand the mechanisms by which kisspeptin influences endometriosis. Full article

Background: Adolescence is the period of life between the ages of 10 and 19. This period is essentially dominated by puberty. The first menstruation, called menarche, occurs, on average, at the age of 12–13. The period after menarche, especially the first 2 years, is characterized by anovulatory cycles, which can be accompanied by menstrual irregularities. This review aims to describe the current status of the diagnostic and therapeutic challenges of the physiological and pathological causes of menstrual irregularities in adolescence and evaluates the benefits from interdisciplinary collaboration to ensure optimal care. Methods: A systematic literature search was conducted in the PubMed database in April 2024 using the following term: “menstrual disorder adolescence”. A total of 1724 abstracts were screened, and relevant articles from the last 10 years were included. In addition, a supplementary topic-relevant literature search of the guidelines of the European Society of Human Reproduction and Embryology (ESHRE) and the guidelines of the Arbeitsgemeinschaft der wissenschaftlichen medizinischen Fachgesellschaft (awmf) was carried out. Results: In addition to cycle irregularities that occur physiologically as a result of anovulatory cycles in the context of the immaturity of the hypothalamic–pituitary–gonadal axis, there are other cycle abnormalities that can be classified as pathological and need to be recognized and treated. Conclusions: Increasing awareness of the various specialist disciplines of physiological and pathological cycle abnormalities in adolescence and interdisciplinary cooperation between them can have a positive influence on the quality of life of adolescent women with cycle abnormalities. Full article

Background: Oestradiol has been implicated as a factor in substrate utilisation in male and mouse studies but the effect of acute changes during the menstrual cycle is yet to be fully understood. Objective: To determine the role of oestradiol in respiratory exchange ratio (RER) during exercise at various intensities. Methods: This systematic review was conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. From inception to November 2023, four online databases (Cochrane, SPORTDiscus, MEDline and Web of Science) were searched for relevant articles. Studies that reported a resting oestradiol measurement in naturally menstruating women with exercise at a percentage of maximal aerobic capacity (%V˙O_2max) were included. Mean and standard deviation for oestradiol, RER and exercise intensity were extracted and study quality assessed using a modified Downs and Black checklist. Risk of bias was assessed using I₂ measure of heterogeneity and Egger’s regression test, assessment of bias from methodological quality was identified by sensitivity analysis. Eligible datasets were extracted for pairwise comparisons within a meta-analysis and correlation between change in oestradiol and change in RER. Data were also pooled to produce a mean and standard deviation for RER for menstrual stage and for low and high oestradiol groups. Results: Twenty-four articles were identified, over 50% were identified as high quality. Sixteen articles included datasets eligible for meta-analysis. Eleven articles utilised a submaximal constant-load exercise intensity, finding a standardised mean difference of − 0.09 ([CI: −0.35–0.17], p = 0.5) suggesting no effect of menstrual phase on constant-load exercise RER. In six articles using incremental exercise tests to exhaustion, a standardised mean difference of 0.60 ([CI 0.00–1.19], p = 0.05) was identified towards a higher maximal RER attained in follicular compared to luteal phase. There was no correlation (R = −0.26, p = 0.2) between change in oestradiol and change in RER between phases. All 24 articles, totalling 650 participants, were included in pooled analysis. When grouped by menstrual cycle phase or when grouped by oestradiol levels, RER was higher in the follicular phase than the luteal phase at low and high constant load exercise intensities. Discussion: Findings from the pooled-analysis and meta-analysis suggest that there may be menstrual cycle phase differences in RER that are intensity dependent. These differences may be related to sex hormone levels, but this was not supported by evidence of correlation between differences in RER and differences in oestradiol. At present, it remains best practice to assess performance in the same menstrual cycle phase if seeking to assess change from baseline. Full article

Background and Clinical Significance: Symptoms of spontaneous intracranial hypotension include orthostatic headaches due to decreased cerebrospinal fluid (CSF) levels. Here, we present a 24-year-old female admitted to an obstetrics and gynecology department with primary complaints of lower abdominal pain and dysmenorrhea with subsequent diagnosis of spontaneous intracranial hypotension (SIH). Case Presentation: The patient had experienced nausea and lower abdominal pain independent of her menstrual cycle 5 days before admission, for which she visited the emergency department 3 days later. On admission, her symptoms were temporarily relieved by administering analgesics; thus, she was discharged. However, later, the symptoms worsened. Consequently, she returned to the emergency department for further evaluation, including blood tests, imaging, and endoscopy, which revealed no nausea- or abdominal pain-related organic abnormalities. On day 10, she developed a headache, aggravated by lying in the supine position and improved by sitting. Additional history revealed a diagnosis of SIH owing to the worsening abdominal pain in the supine position. An ¹¹¹In CSF cavity scintigram showed no spinal fluid leakage; early intrabladder radioisotope (RI) accumulation was observed, and the residual 24 h CSF cavity RI was >30%. At a referral specialist hospital, an epidural saline infusion test was performed, which improved her headache and lower abdominal pain. Blood patch therapy improved her lower abdominal pain, headache, and dysmenorrhea. Conclusions: The final diagnosis was SIH, with symptoms attributed to CSF depletion. The patient also experienced rare paradoxical postural-related headaches and lower abdominal pain, aggravated by lying in the supine position, contributing to the final diagnosis. Full article

Background and Objectives: A similar secretory pattern of prolactin (PRL) and growth hormone (GH) during the menstrual cycle has been reported in response to a high dose of ghrelin in adult healthy women. The present study aimed to assess the pattern of PRL and GH secretions in response to a submaximal dose of ghrelin during different menstrual phases in adult healthy women. Materials and Methods: Eight female subjects with normal cyclicity were enrolled. These subjects were either in the early follicular (EF), late follicular (LF), or mid-luteal (ML) phase of their cycles. Each subject received an IV dose of normal saline (2 mL each time) during the first cycle after enrollment, followed by an IV dose of ghrelin (0.30 μg/kg bw) in the second cycle. The blood samples were collected before and after the IV dosage at −15, 0, 15, 30, 45, 60, 75, 90 and 120 min, where 0 min denotes the time of IV dosage. Results: All the enrolled subjects experienced ovulatory cycles as assessed by increased serum progesterone levels. Serum estradiol levels were significantly higher in the LF than in the EF (p < 0.001) and ML phases (p < 0.01); these levels were also significantly higher in the ML than in the EF phase (p < 0.01). The administration of saline did not affect serum GH or PRL levels. Following the administration of ghrelin, plasma ghrelin levels and serum GH levels increased significantly (p < 0.001). The response amplitude of GH was similar in the three stages of cycle 2. In contrast to GH, the ghrelin injection induced a significant increase in serum PRL levels only in the LF phase (p < 0.05). Conclusions: These results show, for the first time, a different pattern of PRL and GH in response to a submaximal dose of ghrelin during the normal menstrual cycle. It is suggested that the ghrelin threshold for pituitary lactotrophs is higher than for somatotrophs and that, unlike GH, ghrelin-stimulated PRL secretion can be influenced by ovarian steroids. Full article

Uterine physiology encompasses the intricate processes governing the structure, function, and regulation of the uterus, a pivotal organ within the female reproductive system. The escalating prevalence of obesity has emerged as a significant global health issue, profoundly impacting various facets of well-being, including female reproductive health. These effects extend to uterine structure and function, influencing reproductive health outcomes in women. They encompass alterations in uterine morphology, disruptions in hormonal signaling, and inflammatory processes. Insulin and leptin, pivotal hormones regulating metabolism, energy balance, and reproductive function, play crucial roles in this context. Insulin chiefly governs glucose metabolism and storage, while leptin regulates appetite and energy expenditure. However, in obesity, resistance to both insulin and leptin can develop, impacting uterine function. Inflammation and oxidative stress further exacerbate the development of uterine dysfunction in obesity. Chronic low-grade inflammation and heightened oxidative stress, characteristic of obesity, contribute to metabolic disruptions and tissue damage, including within the uterus. Obesity significantly disrupts menstrual cycles, fertility, and pregnancy outcomes in women. The accumulation of excess adipose tissue disrupts hormonal equilibrium, disturbs ovarian function, and fosters metabolic irregularities, all of which detrimentally impact reproductive health. Full article

The concept of “period poverty” describes the lack of access to menstrual health education and menstrual care products. This quasi-experimental mixed-methods study evaluated a collaboration called Just 4U™ to address period poverty. This collaboration was formed between My Vital Cycles^®, as the provider of educational content, and Modibodi^®, as the provider of period pants as a reusable menstrual product (RMP). Five co-educational schools, including a regional school, participated and were of average to below-average socio-educational advantage ranking in Australia. The pre- and post-intervention evaluation with 63 postmenarcheal adolescents (14–18-year-old) in Grades 9–12 showed an improvement in their ovulatory menstrual health literacy. Open-ended questions explored their perspectives on the RMP. Overall, the RMP was well received by participants, who reported a positive impact on their mindset and cycle management. School staff (n = 6) who had observed delivery of Just 4U™ were interviewed. They believed the program had benefited the participants and recommended that teacher training would help the intervention to be sustainably implemented in schools. Findings highlight the worthwhile inclusion of RMPs alongside ovulatory menstrual health education. This study contributes to ongoing research in adolescent ovulatory menstrual health education. Full article

This review presents current opinions on an uncommon condition called catamenial pneumothorax (CP), which is usually associated with thoracic endometriosis syndrome (TES). TES is characterized by the presence of endometriotic lesions in pleura and lung parenchyma and presents with various clinical signs and symptoms, including catamenial pneumothorax. Their diagnosis is often delayed. Pulmonary endometric lesions, however, often detected in patients with hemothorax and hemoptysis, may be absent in a proportion of cases of pneumothorax. The typical presentation of CP includes signs and symptoms of pneumothorax, which occur along with menstruation, most commonly around 24 h before and 48–72 h after its onset. However, they may not occur during every menstrual cycle. Suggestive CP lesions on conventional radiography (RTG) include pneumoperitoneum accompanying right-sided pneumothorax, lung opacities, pleural effusion, and nodular infiltrates. Chest and abdomen computed tomography (CT), particularly contrast-enhanced, may additionally show pneumoperitoneum and diaphragmatic lesions. The management of CP includes supportive treatment of acute symptoms and causal treatment to prevent recurrent disease. This article presents the pathophysiology of CP, an overview of the diagnostic methods, and the current therapeutic approaches. The necessity for a multidisciplinary approach to the diagnosis of CP and to the choice of the best treatment modality is underlined (promising new therapeutic options are also mentioned); however, international guidelines are still missing. Full article

Background/Objectives: Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women of fertile age. Some studies suggest that a ketogenic diet (KD) may have a role in treating PCOS. We aimed to demonstrate the long-term effectiveness of a KD in PCOS. Methods: Eighteen patients with PCOS phenotype A were enrolled: 28% were of normal weight, 28% were overweight, and 44% had obesity. All participants followed a KD without meal replacements for 45 days. After this period, patients underwent gradual carbohydrate reintroduction over 45 days, and thereafter healthy eating indications were given. Twelve patients completed the study. The patients were assessed at baseline and after 6 months. Anthropometric data, body composition, pelvic ultrasound, blood chemistry, hirsutism, and menstrual cycles frequency were recorded; Results: Besides improvement in anthropometric parameters, menstrual cycles (p 0.012), ovarian volume (p 0.029), FSH (p 0.05), LH (p 0.037), and progesterone (p 0.017) improved independently of weight or fat loss. However, testosterone and hirsutism improvements were influenced by weight and fat mass reduction. Conclusions: Our study showed that a KD followed by gradual carbohydrate reintroduction in PCOS has beneficial effects medium term, mostly independent of body weight loss, even in normal-weight women, suggesting that nutritional ketosis exerts beneficial effects per se. Full article

This study aimed to identify unique characteristics in the peripheral blood mononuclear cells (PBMCs) of endometriosis patients and develop a non-invasive early diagnostic tool. Using single-cell RNA sequencing (scRNA-seq), we constructed the first single-cell atlas of PBMCs from endometriosis patients based on 107,964 cells and 25,847 genes. Within CD16⁺ monocytes, we discovered JUP as a dysregulated gene. To assess its diagnostic potential, we measured peritoneal fluid (PF) and serum JUP levels in a large cohort of 199 patients including 20 women with ovarian cancer (OC). JUP was barely detectable in PF but was significantly elevated in the serum of patients with endometriosis and OC, with levels 1.33 and 2.34 times higher than controls, respectively. Additionally, JUP was found in conditioned culture media of CD14⁺/CD16⁺ monocytes aligning with our scRNA-seq data. Serum JUP levels correlated with endometriosis severity and endometrioma presence but were unaffected by dysmenorrhea, menstrual cycle, or adenomyosis. When combined with CA125 (cancer antigen 125) JUP enhanced the specificity of endometriosis diagnosis from 89.13% (CA125 measured alone) to 100%. While sensitivity remains a challenge at 19%, our results suggest that JUP’s potential to enhance diagnostic accuracy warrants additional investigation. Furthermore, employing serum JUP as a stratification marker unlocked the potential to identify additional endometriosis-related genes, offering novel insights into disease pathogenesis. Full article

This Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) systematic review synthesized effects of background levels of per- and polyfluorylalkyl substance (PFAS) levels on reproductive health outcomes in the general public: fertility, preterm birth, miscarriage, ovarian health, menstruation, menopause, sperm health, and in utero fetal growth. The inclusion criteria included original research (or primary) studies, human subjects, and investigation of outcomes of interest following non-occupational exposures. It drew from four databases (Web of Science, PubMed, Embase and Health and Environmental Research Online (HERO)) using a standardized search string for all studies published between 1 January 2017 and 13 April 2022. Risk of bias was assessed by two independent reviewers. Data were extracted and reviewed by multiple reviewers. Each study was summarized under its outcome in terms of methodology and results and placed in context, with recommendations for future research. Of 1712 records identified, 30 were eligible, with a total of 27,901 participants (33 datasets, as three studies included multiple outcomes). There was no effect of background levels of PFAS on fertility. There were weakly to moderately increased odds of preterm birth with higher perfluorooctane sulfonic acid (PFOS) levels; the same for miscarriage with perfluorooctanoic acid (PFOA) levels. There was limited yet suggestive evidence for a link between PFAS and early menopause and primary ovarian insufficiency; menstrual cycle characteristics were inconsistent. PFAS moderately increased odds of PCOS- and endometriosis-related infertility, respectively. Sperm motility and DNA health were moderately impaired by multiple PFAS. Fetal growth findings were inconsistent. This review may be used to inform forthcoming drinking water standards and policy initiatives regarding PFAS compounds and drinking water. Future reviews would benefit from more recent studies. Larger studies in these areas are warranted. Future studies should plan large cohorts and open access data availability to capture small effects and serve the public. Funding: Great Lakes Water Authority (Detroit, MI), the Erb Family Foundation through Healthy Urban Waters at Wayne State University (Detroit, MI), and Wayne State University CLEAR Superfund Research (NIH P42ES030991). Full article

Background/Objectives: Premenstrual syndrome (PMS), a clinical condition that manifests in the form of various physical and psychological symptoms, occurs periodically during the luteal phase of the menstrual cycle and reduces quality of life. Methods: Here, we conducted in vitro and in vivo experiments to investigate the effects of Lactobacillus helveticus HY7801 (HY7801) on PMS symptoms. Results: Data from the in vitro experiments showed that HY7801 inhibits prolactin secretion by estradiol-induced GH3 cells, as well as the secretion of pro-inflammatory cytokines by LPS-induced Raw 264.7 cells. Additionally, the oral administration of HY7801 (10⁹ colony-forming units/kg/day) to mice with metoclopramide-induced hyperprolactinemia reduced uterine tissue mass and endometrial thickness, both of which were increased excessively in the presence of prolactin. HY7801 also regulated the serum levels of follicle-stimulating hormone and prostaglandin E1/E2, as well as recovering the progesterone/estradiol ratio. HY7801 also downregulated the serum levels of prolactin and pro-inflammatory cytokines such as interleukin (Il)-6, tumor necrosis factor-alpha (Tnf), and IL-1β. Finally, HY7801 reduced the expression of genes encoding inflammatory cytokines (i.e., Tnf and Il-6), cyclooxygenase-2 (Cox-2), and inducible nitric oxide synthase (iNOS) in mice with hyperprolactinemia. Conclusion: In summary, HY7801 may be a functional bacterium that alleviates PMS symptoms by modulating hormones and inflammatory markers. Full article

Autophagy is a cellular process crucial for maintaining homeostasis by degrading damaged proteins and organelles. It is stimulated in response to stress, recycling nutrients and generating energy for cell survival. In normal endometrium, it suppresses tumorigenesis by preventing toxic accumulation and maintaining cellular homeostasis. It is involved in the cyclic remodelling of the endometrium during the menstrual cycle and contributes to decidualisation for successful pregnancy. Such a process is regulated by various signalling pathways, including PI3K/AKT/mTOR, AMPK/mTOR, and p53. Dysregulation of autophagy has been associated with benign conditions like endometriosis and endometrial hyperplasia but also with malignant neoplasms such as endometrial carcinoma. In fact, it has emerged as a crucial player in endometrial carcinoma biology, exhibiting a dual role in both tumour suppression and tumour promotion, providing nutrients during metabolic stress and allowing cancer cell survival. It also regulates cancer stem cells, metastasis and therapy resistance. Targeting autophagy is therefore a promising therapeutic strategy in endometrial carcinoma and potential for overcoming resistance to standard treatments. The aim of this review is to delve into the intricate details of autophagy’s role in endometrial pathology, exploring its mechanisms, signalling pathways and potential therapeutic implications. Full article

This study aimed to evaluate the concentration of osteopontin in peritoneal fluid and plasma as potential biomarkers for diagnosing endometriosis. Osteopontin levels were measured using surface plasmon resonance imaging (SPRI) biosensors in patients suspected of having endometriosis. Plasma samples were collected from 120 patients, and peritoneal fluid was collected from 86 patients. Based on the detection of endometriosis lesions during laparoscopy, participants were divided into a study group (patients with endometriosis) and a control group (patients without endometriosis). The results showed no significant differences in plasma osteopontin levels between women with endometriosis and the control group (19.86 ± 6.72 ng/mL vs. 18.39 ± 4.46 ng/mL, p = 0.15). Similarly, peritoneal fluid osteopontin concentrations did not differ significantly between patients with and without endometriosis (19.04 ± 5.37 ng/mL vs. 17.87 ± 5.13 ng/mL, p = 0.29). Furthermore, osteopontin levels in both plasma and peritoneal fluid were not significantly associated with the stage of endometriosis, the presence of endometrioma, or the menstrual cycle phase. The findings of this study do not support osteopontin concentration as a reliable biomarker for endometriosis. However, further research is necessary to explore osteopontin’s potential role in the disease. Full article

Endometrial disorders, such as infertility and endometriosis, significantly impact reproductive health, thus necessitating better models to study endometrial function. Current in vitro models fail to replicate the complexity of the human endometrium throughout the entire menstrual cycle. This study aimed to assess the physiological response of human endometrial organoids (hEOs) to in vitro hormonal treatments designed to mimic the hormonal fluctuations of the menstrual cycle. Endometrial biopsies from three healthy women were used to develop hEOs, which were treated over 28 days with three hormonal stimulation strategies: (1) estrogen only (E) to mimic the proliferative phase, (2) the addition of progesterone (EP) to simulate the secretory phase, and (3) the further addition of cAMP (EPC) to enhance the secretory functions of hEOs. Gene and protein expression were analyzed using qPCR, IHC, and ELISA. The hEOs exhibited proliferation, gland formation, and appropriate expression of markers such as E-cadherin and Ki67. The hormonal treatments induced significant changes in PR, HSD17B1, PAEP, SPP1, and other genes relevant to endometrial function, closely mirroring in vivo physiological responses. The prominent changes were observed in EPC-treated hEOs (week 4) with significantly high expression of uterine milk components such as glycodelin (PAEP) and osteopontin (SPP1), reflecting mid- to late-secretory phase physiology. This model successfully recapitulates human menstrual cycle dynamics and offers a promising platform for studying endometrial disorders and advancing personalized treatments in gynecology. Full article