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Endocrine Reviews Jul 2020More than 1 out of 10 women worldwide are diagnosed with polycystic ovary syndrome (PCOS), the leading cause of female reproductive and metabolic dysfunction. Despite... (Review)
Review
More than 1 out of 10 women worldwide are diagnosed with polycystic ovary syndrome (PCOS), the leading cause of female reproductive and metabolic dysfunction. Despite its high prevalence, PCOS and its accompanying morbidities are likely underdiagnosed, averaging > 2 years and 3 physicians before women are diagnosed. Although it has been intensively researched, the underlying cause(s) of PCOS have yet to be defined. In order to understand PCOS pathophysiology, its developmental origins, and how to predict and prevent PCOS onset, there is an urgent need for safe and effective markers and treatments. In this review, we detail which animal models are more suitable for contributing to our understanding of the etiology and pathophysiology of PCOS. We summarize and highlight advantages and limitations of hormonal or genetic manipulation of animal models, as well as of naturally occurring PCOS-like females.
Topics: Animals; Disease Models, Animal; Female; Humans; Polycystic Ovary Syndrome
PubMed: 32310267
DOI: 10.1210/endrev/bnaa010 -
Nature Cell Biology Aug 2022Endometriosis is characterized by the growth of endometrial-like tissue outside the uterus. It affects many women during their reproductive age, causing years of pelvic...
Endometriosis is characterized by the growth of endometrial-like tissue outside the uterus. It affects many women during their reproductive age, causing years of pelvic pain and potential infertility. Its pathophysiology remains largely unknown, which limits early diagnosis and treatment. We characterized peritoneal and ovarian lesions at single-cell transcriptome resolution and compared them to matched eutopic endometrium, unaffected endometrium and organoids derived from these tissues, generating data on over 122,000 cells across 14 individuals. We spatially localized many of the cell types using imaging mass cytometry. We identify a perivascular mural cell specific to the peritoneal lesions, with dual roles in angiogenesis promotion and immune cell trafficking. We define an immunotolerant peritoneal niche, fundamental differences in eutopic endometrium and between lesion microenvironments and an unreported progenitor-like epithelial cell subpopulation. Altogether, this study provides a holistic view of the endometriosis microenvironment that represents a comprehensive cell atlas of the disease in individuals undergoing hormonal treatment, providing essential information for future therapeutics and diagnostics.
Topics: Choristoma; Endometriosis; Endometrium; Female; Humans; Ovarian Cysts; Ovarian Neoplasms; Single-Cell Analysis; Tumor Microenvironment
PubMed: 35864314
DOI: 10.1038/s41556-022-00961-5 -
Cell Reports. Medicine Dec 2022Tumor-infiltrating lymphocytes (TILs), especially CD8 TILs, represent a favorable prognostic factor in high-grade serous ovarian cancer (HGSOC) and other tumor lineages....
Tumor-infiltrating lymphocytes (TILs), especially CD8 TILs, represent a favorable prognostic factor in high-grade serous ovarian cancer (HGSOC) and other tumor lineages. Here, we analyze the spatial heterogeneity of different TIL subtypes in HGSOC. We integrated RNA sequencing, whole-genome sequencing, bulk T cell receptor (TCR) sequencing, as well as single-cell RNA/TCR sequencing to investigate the characteristics and differential composition of TILs across different HGSOC sites. Two immune "cold" patterns in ovarian cancer are identified: (1) ovarian lesions with low infiltration of mainly dysfunctional T cells and immunosuppressive Treg cells and (2) omental lesions infiltrated with non-tumor-specific bystander cells. Exhausted CD8 T cells that are preferentially enriched in ovarian tumors exhibit evidence for expansion and cytotoxic activity. Inherent tumor immune microenvironment characteristics appear to be the main contributor to the spatial differences in TIL status. The landscape of spatial heterogeneity of TILs may inform potential strategies for therapeutic manipulation in HGSOC.
Topics: Humans; Female; Ovarian Neoplasms; Prognosis; Multiomics; Ovarian Cysts; Receptors, Antigen, T-Cell; Tumor Microenvironment
PubMed: 36543113
DOI: 10.1016/j.xcrm.2022.100856 -
American Family Physician Apr 2016Adnexal masses can have gynecologic or nongynecologic etiologies, ranging from normal luteal cysts to ovarian cancer to bowel abscesses. Women who report abdominal or... (Review)
Review
Adnexal masses can have gynecologic or nongynecologic etiologies, ranging from normal luteal cysts to ovarian cancer to bowel abscesses. Women who report abdominal or pelvic pain, increased abdominal size or bloating, difficulty eating, or rapid satiety that occurs more than 12 times per month in less than a year should be evaluated for ovarian cancer. Pelvic examination has low sensitivity for detecting an adnexal mass; negative pelvic examination findings in a symptomatic woman should not deter further workup. Ectopic pregnancy must be ruled out in women of reproductive age. A cancer antigen 125 (CA 125) test may assist in the evaluation of an adnexal mass in appropriate patients. CA 125 levels are elevated in conditions other than ovarian cancer. Because substantial overlap in CA 125 levels between pre- and postmenopausal women may occur, this level alone is not recommended for differentiating between a benign and a malignant adnexal mass. Transvaginal ultrasonography is the first choice for imaging of an adnexal mass. Large mass size, complexity, projections, septation, irregularity, or bilaterality may indicate cancer. If disease is suspected outside of the ovary, computed tomography may be indicated; magnetic resonance imaging may better show malignant characteristics in the ovary. Serial ultrasonography and periodic measurement of CA 125 levels may help in differentiating between benign or potentially malignant adnexal masses. If an adnexal mass larger than 6 cm is found on ultrasonography, or if findings persist longer than 12 weeks, referral to a gynecologist or gynecologic oncologist is indicated.
Topics: Adnexal Diseases; CA-125 Antigen; Chorionic Gonadotropin, beta Subunit, Human; Diagnosis, Differential; Endometriosis; Female; Gynecological Examination; Humans; Leiomyoma; Magnetic Resonance Imaging; Ovarian Cysts; Ovarian Diseases; Ovarian Neoplasms; Pelvic Inflammatory Disease; Practice Guidelines as Topic; Pregnancy; Pregnancy, Ectopic; Tomography, X-Ray Computed; Torsion Abnormality; Ultrasonography; Uterine Neoplasms
PubMed: 27175840
DOI: No ID Found -
Fertility and Sterility Oct 2022Ovulatory disorders are common causes of amenorrhea, abnormal uterine bleeding, and infertility, and are frequent manifestations of polycystic ovary syndrome (PCOS)....
Ovulatory disorders are common causes of amenorrhea, abnormal uterine bleeding, and infertility, and are frequent manifestations of polycystic ovary syndrome (PCOS). There are many potential causes and contributors to ovulatory dysfunction that challenge clinicians, trainees, educators, and those who perform basic, translational, clinical, and epidemiological research. Similarly, therapeutic approaches to ovulatory dysfunction potentially involve a spectrum of lifestyle, psychological, medical, and procedural interventions. Collaborative research, effective education, and consistent clinical care remain challenged by the absence of a consensus comprehensive system for classification of these disorders. The existing and complex system, attributed to WHO, was developed more than three decades ago and did not consider more than 30 years of research into these disorders in addition to technical advances in imaging and endocrinology. This manuscript describes the development of a new classification of ovulatory disorders performed under the aegis of the International Federation of Gynecology and Obstetrics (FIGO) and conducted using a rigorously applied Delphi process. The stakeholder organizations and individuals who participated in this process comprised specialty journals, experts at large, national, specialty obstetrical and gynecological societies, and informed lay representatives. After two face-to-face meetings and five Delphi rounds, the result is a three-level multi-tiered system. The system is applied after a preliminary assessment identifies the presence of an ovulatory disorder. The primary level of the system is based on an anatomic model (Hypothalamus, Pituitary, Ovary) that is completed with a separate category for PCOS. This core component of the system is easily remembered using the acronym HyPO-P. Each anatomic category is stratified in the second layer of the system to provide granularity for investigators, clinicians, and trainees using the "GAIN-FIT-PIE" mnemonic (Genetic, Autoimmune, Iatrogenic, Neoplasm; Functional, Infectious and Inflammatory, Trauma and vascular; Physiological, Idiopathic, Endocrine). The tertiary level allows for specific diagnostic entities. It is anticipated that, if widely adopted, this system will facilitate education, clinical care, and the design and interpretation of research in a fashion that better informs progress in this field. Integral to the deployment of this system is a periodic process of reevaluation and appropriate revision, reflecting an improved understanding of this collection of disorders.
Topics: Endocrinology; Female; Gynecology; Humans; Polycystic Ovary Syndrome; Pregnancy; Uterine Diseases
PubMed: 35995633
DOI: 10.1016/j.fertnstert.2022.07.009 -
Advances in Clinical and Experimental... Mar 2019An approach to ovarian endometrial cysts has changed considerably during recent years, especially in regard to treatment of recurrent endometriosis, fertility sparing... (Review)
Review
An approach to ovarian endometrial cysts has changed considerably during recent years, especially in regard to treatment of recurrent endometriosis, fertility sparing and infertility management. Surgical treatment is the primary therapeutic option. The most efficient types of treatment are radical procedures involving adhesiolysis, removal of the cyst along with its capsule and any remaining endometriotic foci. However, small asymptomatic cysts should not be treated surgically, especially in patients older than 35 years. Surgical treatment can be considered in infertile women and those who failed to get pregnant despite 1-1.5 years of trials, as well as in cases in which in vitro fertilization is not an option. Also large cysts, with more than 4 cm in diameter, should be treated surgically due to the risk of their rupture or torsion. The most efficient preventive measure for recurrent ovarian endometriosis is unilateral oophorectomy with sparing the contralateral ovary. Such a procedure should be considered in women who are no longer interested in childbearing or present with another endometriotic cyst in the same ovary. The role of pharmacotherapy is fairly limited; it should be considered in patients in whom diffuse endometriosis is associated with pain. Therapeutic agents from the following groups can be used: estrogen-progestin preparation, gestagens, including progesteronereleasing intrauterine systems and gonadotropin-releasing hormone agonists. Women with infertility should get pregnant as soon as possible, and in patients who failed to get pregnant and/or are older than 35 years, in vitro fertilization should be the treatment of choice.
Topics: Endometriosis; Endometrium; Female; Humans; Infertility, Female; Laparoscopy; Neoplasm Recurrence, Local; Ovarian Cysts; Ovariectomy; Pregnancy
PubMed: 30659784
DOI: 10.17219/acem/90767 -
Radiologia 2017Acute pelvic pain is a common condition in emergency. The sources of acute pelvic pain are multifactorial, so it is important to be familiar with this type of...
Acute pelvic pain is a common condition in emergency. The sources of acute pelvic pain are multifactorial, so it is important to be familiar with this type of pathologies. The purpose of this article is review the main causes of gynecological acute pelvic pain and their radiologic appearances to be able to make an accurate diagnosis and provide objective criteria for patient management.
Topics: Acute Pain; Diagnosis, Differential; Emergencies; Endometriosis; Female; Genital Diseases, Female; Humans; Ovarian Cysts; Pelvic Inflammatory Disease; Pelvic Pain; Pregnancy; Pregnancy, Ectopic; Torsion Abnormality
PubMed: 27979433
DOI: 10.1016/j.rx.2016.09.010 -
The Indian Journal of Medical Research Oct 2019Polycystic ovary syndrome (PCOS) is a common endocrine disorder predominantly affecting women of reproductive age. Clinical manifestations are diverse including... (Review)
Review
Polycystic ovary syndrome (PCOS) is a common endocrine disorder predominantly affecting women of reproductive age. Clinical manifestations are diverse including hyperandrogenism, anovulation, infertility and increased risk of metabolic diseases besides psychosocial dysfunction. This review provides information on the problem of PCOS in India, its pathophysiology, genetics and an overview of current management options to instigate further research in this field. Prevalence of PCOS in India ranges from 3.7 to 22.5 per cent depending on the population studied and the criteria used for diagnosis. Abnormalities in leptin-adiponectin (adipocyte biology), oxidative stress and autoimmunity are among the mechanisms studied regarding pathogenesis of PCOS. Many candidate gene studies have shown associations with PCOS in various studies. Studies have consistently demonstrated the relationship between the well-known manifestation of hyperandrogenism among Indian PCOS women and the metabolic morbidities including insulin resistance, glucose intolerance and cardiovascular risk. Management of individual components of PCOS can be achieved by medications or surgical methods, though further clarification regarding pathogenesis of PCOS is needed to sharpen our therapeutic armamentarium.
Topics: Female; Humans; India; Polycystic Ovary Syndrome
PubMed: 31823915
DOI: 10.4103/ijmr.IJMR_1937_17 -
Endocrine Reviews Oct 2015Polycystic ovary syndrome (PCOS) is a heterogeneous and complex disorder that has both adverse reproductive and metabolic implications for affected women. However, there... (Review)
Review
Polycystic ovary syndrome (PCOS) is a heterogeneous and complex disorder that has both adverse reproductive and metabolic implications for affected women. However, there is generally poor understanding of its etiology. Varying expert-based diagnostic criteria utilize some combination of oligo-ovulation, hyperandrogenism, and the presence of polycystic ovaries. Criteria that require hyperandrogenism tend to identify a more severe reproductive and metabolic phenotype. The phenotype can vary by race and ethnicity, is difficult to define in the perimenarchal and perimenopausal period, and is exacerbated by obesity. The pathophysiology involves abnormal gonadotropin secretion from a reduced hypothalamic feedback response to circulating sex steroids, altered ovarian morphology and functional changes, and disordered insulin action in a variety of target tissues. PCOS clusters in families and both female and male relatives can show stigmata of the syndrome, including metabolic abnormalities. Genome-wide association studies have identified a number of candidate regions, although their role in contributing to PCOS is still largely unknown.
Topics: Diagnosis, Differential; Female; Humans; Polycystic Ovary Syndrome
PubMed: 26426951
DOI: 10.1210/er.2015-1018