RESUMEN
BACKGROUND: Premature ovarian failure (POF) is a clinical condition characterized by the cessation of ovarian function, leading to infertility. The underlying molecular mechanisms remain unclear, and no predictable biomarkers have been identified. This study aimed to investigate the protein and metabolite contents of serum extracellular vesicles to investigate underlying molecular mechanisms and explore potential biomarkers. METHODS: This study was conducted on a cohort consisting of 14 POF patients and 16 healthy controls. The extracellular vesicles extracted from the serum of each group were subjected to label-free proteomic and unbiased metabolomic analysis. Differentially expressed proteins and metabolites were annotated. Pathway network clustering was conducted with further correlation analysis. The biomarkers were confirmed by ROC analysis and random forest machine learning. RESULTS: The proteomic and metabolomic profiles of POF patients and healthy controls were compared. Two subgroups of POF patients, Pre-POF and Pro-POF, were identified based on the proteomic profile, while all patients displayed a distinguishable metabolomic profile. Proteomic analysis suggested that inflammation serves as an early factor contributing to the infertility of POF patients. For the metabolomic analysis, despite the dysfunction of metabolism, oxidative stress and hormone imbalance were other key factors appearing in POF patients. Signaling pathway clustering of proteomic and metabolomic profiles revealed the progression of dysfunctional energy metabolism during the development of POF. Moreover, correlation analysis identified that differentially expressed proteins and metabolites were highly associated, with six of them being selected as potential biomarkers. ROC curve analysis, together with random forest machine learning, suggested that AFM combined with 2-oxoarginine was the best diagnostic biomarker for POF. CONCLUSIONS: Omics analysis revealed that inflammation, oxidative stress, and hormone imbalance are factors that damage ovarian tissue, but the progressive dysfunction of energy metabolism might be the critical pathogenic pathway contributing to the development of POF. AFM combined with 2-oxoarginine serves as a precise biomarker for clinical POF diagnosis.
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Biomarcadores , Metabolismo Energético , Vesículas Extracelulares , Metabolómica , Insuficiencia Ovárica Primaria , Proteómica , Humanos , Femenino , Vesículas Extracelulares/metabolismo , Biomarcadores/sangre , Metabolismo Energético/fisiología , Insuficiencia Ovárica Primaria/sangre , Insuficiencia Ovárica Primaria/diagnóstico , Insuficiencia Ovárica Primaria/metabolismo , Proteómica/métodos , Adulto , Metabolómica/métodos , Progresión de la Enfermedad , Metaboloma/fisiologíaRESUMEN
This article is a summary of normal menstrual bleeding and how to recognize abnormalities based on patient's symptoms as well as identify possible causes in order to direct treatment. This article discusses abnormal uterine bleeding including the definition, etiology, evaluation, and treatment. It also discusses primary ovarian insufficiency, transgender medicine, and menopause.
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Insuficiencia Ovárica Primaria , Humanos , Femenino , Insuficiencia Ovárica Primaria/diagnóstico , Insuficiencia Ovárica Primaria/terapia , Menopausia/fisiología , Hemorragia Uterina/diagnóstico , Hemorragia Uterina/terapia , Atención Primaria de Salud , Enfermedades del Sistema Endocrino/diagnóstico , Trastornos de la Menstruación/diagnóstico , Trastornos de la Menstruación/terapiaRESUMEN
Premature ovarian failure (POF), which is often comorbid with dry eye disease (DED) is a key issue affecting female health. Here, we explored the mechanism underlying comorbid POF and DED to further elucidate disease mechanisms and improve treatment. Datasets related to POF (GSE39501) and DED (GSE44101) were identified from the Gene Expression Omnibus (GEO) database and subjected to weighted gene coexpression network (WGCNA) and differentially expressed genes (DEGs) analyses, respectively, with the intersection used to obtain 158 genes comorbid in POF and DED. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses of comorbid genes revealed that identified genes were primarily related to DNA replication and Cell cycle, respectively. Protein-Protein interaction (PPI) network analysis of comorbid genes obtained the 15 hub genes: CDC20, BIRC5, PLK1, TOP2A, MCM5, MCM6, MCM7, MCM2, CENPA, FOXM1, GINS1, TIPIN, MAD2L1, and CDCA3. To validate the analysis results, additional POF- and DED-related datasets (GSE48873 and GSE171043, respectively) were selected. miRNAs-lncRNAs-genes network and machine learning methods were used to further analysis comorbid genes. The DGIdb database identified valdecoxib, amorfrutin A, and kaempferitrin as potential drugs. Herein, the comorbid genes of POF and DED were identified from a bioinformatics perspective, providing a new strategy to explore the comorbidity mechanism, opening up a new direction for the diagnosis and treatment of comorbid POF and DED.
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Síndromes de Ojo Seco , Redes Reguladoras de Genes , Insuficiencia Ovárica Primaria , Mapas de Interacción de Proteínas , Humanos , Femenino , Síndromes de Ojo Seco/genética , Síndromes de Ojo Seco/diagnóstico , Insuficiencia Ovárica Primaria/genética , Insuficiencia Ovárica Primaria/diagnóstico , Mapas de Interacción de Proteínas/genética , Biomarcadores , Perfilación de la Expresión Génica , Ontología de Genes , Bases de Datos Genéticas , Biología Computacional/métodosRESUMEN
The objective of the study was to evaluate the profile and diagnostic significance of serum autoantibodies in infertile patients with premature ovarian insufficiency (POI). The pilot study included 26 patients of reproductive age with POI and diminished ovarian reserve who received complex treatment using new surgical technologies (Group 1) and 18 patients without POI (Group 2). The profile of serum autoantibodies, including anti-ovarian antibodies, antibodies against thyroid peroxidase (TPO), steroidogenic enzymes, and steroid and gonadotropic hormones, was studied using modified ELISAs and human recombinant steroidogenic enzymes (CYP11A1, CYP19A1, CYP21A2). Patients in Group 1 had higher levels of IgG autoantibodies against steroidogenic enzymes, estradiol, progesterone, and TPO than those in Group 2. Tests for IgG antibodies against CYP11A1, CYP19A1, and CYP21A2 exhibited high sensitivity (65.4-76.9%), specificity (83.3-89.9%), and AUC values (0.842-0.910) for POI, the highest in the first test. Three-antibodies panel screening showed higher diagnostic accuracy (84.1% versus 75-79.6%). The levels of these antibodies correlated with menstrual irregularities and a decrease in the antral follicle count. Thus, antibodies against CYP11A1, CYP19A1, and CYP21A2 have a high diagnostic value for POI. Three-antibody panel screening may improve the accuracy of POI diagnosis and be useful for identifying high-risk groups, early stages of the disease, and predicting POI progression.
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Autoanticuerpos , Enzima de Desdoblamiento de la Cadena Lateral del Colesterol , Infertilidad Femenina , Insuficiencia Ovárica Primaria , Humanos , Femenino , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Insuficiencia Ovárica Primaria/inmunología , Insuficiencia Ovárica Primaria/sangre , Insuficiencia Ovárica Primaria/diagnóstico , Adulto , Infertilidad Femenina/inmunología , Infertilidad Femenina/sangre , Infertilidad Femenina/diagnóstico , Enzima de Desdoblamiento de la Cadena Lateral del Colesterol/inmunología , Aromatasa/inmunología , Esteroide 21-Hidroxilasa/inmunología , Yoduro Peroxidasa/inmunología , Proyectos Piloto , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Biomarcadores/sangre , Progesterona/sangre , Progesterona/inmunología , Estradiol/sangreRESUMEN
Premature Ovarian Insufficiency (POI), also known as Premature Ovarian Failure (POF), is a heterogeneous disorder characterized by the cessation of ovarian function before age 40. Clinical symptoms include menstrual disorders: amenorrhea/oligomenorrhea or symptoms of estrogen deficiency. This review aims to provide the most important summary of the immunophenotypic profile of premature ovarian failure syndrome, along with a review of the latest reports on the usefulness of inflammatory markers. The inflammatory microenvironment in POI applies to many levels. Concomitants of autoimmune ovarian inflammation and impaired cellular immune response may be a picture of impaired regulation in autoimmune ovarian disease. The serum concentration of pro-inflammatory cytokines, like IL-6, IL-8, IL-17, tumor necrosis factor α (TNF-α), and interferon-gamma (IFN-γ), tend to increase, whereas levels of the anti-inflammatory cytokine, IL-10, tend to decrease. In our review, we focus on whether the measured immunological parameters could help in the diagnosis and prognosis of the syndrome. Among the inflammatory markers, neutrophil-to-lymphocyte ratio (NLR) is noteworthy, as it is decreased in patients with POI. It is important to stress that besides case series, we need properly powered studies with randomization to answer which treatment is effective, and how to deal with concurrent autoimmunity. In this review, we emphasize the importance of the premature ovarian failure syndrome immunoprofile for a proper understanding of the complexity of this syndrome, potential diagnostic points, and therapeutic targets.
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Biomarcadores , Citocinas , Insuficiencia Ovárica Primaria , Humanos , Insuficiencia Ovárica Primaria/inmunología , Insuficiencia Ovárica Primaria/diagnóstico , Insuficiencia Ovárica Primaria/sangre , Femenino , Biomarcadores/sangre , Citocinas/sangre , Citocinas/metabolismo , Inmunofenotipificación , Inflamación/inmunología , Inflamación/diagnóstico , Inflamación/sangre , Mediadores de Inflamación/metabolismo , Mediadores de Inflamación/sangre , Neutrófilos/inmunología , Linfocitos/inmunología , Autoinmunidad , AnimalesRESUMEN
OBJECTIVES: Childhood cancer survivors are at risk for premature ovarian insufficiency, especially after treatment with alkylating agents. The objective of this report is to highlight a case in which this phenomenon caused a false-positive pregnancy test. CASE PRESENTATION: A workup was performed in a 14-year-old girl with a positive pregnancy test. She was diagnosed with stage IV neuroblastoma of the left adrenal gland at the age of 4 years. She received extensive treatment, including alkylating agents, and had been diagnosed with premature ovarian insufficiency. An LH/hCG suppression test was performed using high dose 17â¯bèta-estradiol: hCG levels normalized. CONCLUSIONS: The pregnancy test was false-positive due to production of low amounts of hCG by the pituitary gland as a result of high LH concentrations following premature ovarian insufficiency. It may be helpful to perform the LH/hCG suppression test to prove pituitary origin of the hCG overproduction.
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Insuficiencia Ovárica Primaria , Humanos , Femenino , Insuficiencia Ovárica Primaria/diagnóstico , Insuficiencia Ovárica Primaria/patología , Adolescente , Embarazo , Pruebas de Embarazo , Neuroblastoma/complicaciones , Neuroblastoma/patología , Neuroblastoma/tratamiento farmacológico , Neoplasias de las Glándulas Suprarrenales/complicaciones , Neoplasias de las Glándulas Suprarrenales/patología , Neoplasias de las Glándulas Suprarrenales/diagnóstico , Reacciones Falso Positivas , Hormona Luteinizante/sangre , PronósticoRESUMEN
The typical age at menopause is 50-51 years in high-income countries. However, early menopause is common, with around 8% of women in high-income countries and 12% of women globally experiencing menopause between the ages of 40 years and 44 years. Menopause before age 40 years (premature ovarian insufficiency) affects an additional 2-4% of women. Both early menopause and premature ovarian insufficiency can herald an increased risk of chronic disease, including osteoporosis and cardiovascular disease. People who enter menopause at younger ages might also experience distress and feel less supported than those who reach menopause at the average age. Clinical practice guidelines are available for the diagnosis and management of premature ovarian insufficiency, but there is a gap in clinical guidance for early menopause. We argue that instead of distinct age thresholds being applied, early menopause should be seen on a spectrum between premature ovarian insufficiency and menopause at the average age. This Series paper presents evidence for the short-term and long-term consequences of early menopause. We offer a practical framework for clinicians to guide diagnosis and management of early menopause, which considers the nature and severity of symptoms, age and medical history, and the individual's wishes and priorities to optimise their quality of life and short-term and long-term health. We conclude with recommendations for future research to address key gaps in the current evidence.
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Menopausia Prematura , Osteoporosis , Insuficiencia Ovárica Primaria , Femenino , Humanos , Adulto , Calidad de Vida , Insuficiencia Ovárica Primaria/diagnóstico , Insuficiencia Ovárica Primaria/etiología , Menopausia , Osteoporosis/diagnóstico , Osteoporosis/prevención & controlRESUMEN
The prediction of menopause and premature ovarian insufficiency (POI) involves understanding the factors that contribute to the timing of these events. Menopause is a natural biological process marked by the cessation of menstrual periods, typically occurring around the age of 51. On the other hand, POI refers to the loss of ovarian function before the age of 40. Several factors have been used to predict menopause and POI such as age, antimüllerian hormone, inhibins and follicle-stimulating hormone serum levels, antral follicle counts, menstrual cycle length, and, recently, some genetic markers. It seems that age has the best predictive power and all the other ones are only adding in a very limited way to the prediction of menopause. Low levels of antimüllerian hormone in young women might indicate a greater risk for POI and could facilitate early diagnosis. It is, however, important to note that predicting the exact timing of menopause and POI is challenging, and individual variations are significant. Although these factors can provide some insights, they are not foolproof predictors. Advances in medical research and technology may lead to more accurate methods for predicting menopause and POI in the future.
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Menopausia , Insuficiencia Ovárica Primaria , Humanos , Femenino , Insuficiencia Ovárica Primaria/sangre , Insuficiencia Ovárica Primaria/diagnóstico , Insuficiencia Ovárica Primaria/fisiopatología , Menopausia/sangre , Valor Predictivo de las Pruebas , Factores de Riesgo , Biomarcadores/sangre , Adulto , Factores de Edad , Hormona Antimülleriana/sangre , Menopausia Prematura/sangre , Persona de Mediana EdadRESUMEN
Acyl-CoA-binding domain-containing protein 5-related retinal dystrophy with leukodystrophy (ACBD5) is a peroxisomal disorder due to deficiency of ACBD5. Presenting features include retinal dystrophy, progressive leukodystrophy, and ataxia. Only seven cases of ACBD5-related retinal dystrophy have been reported in the literature to date, including one other case diagnosed in adulthood. Here we report a case with novel compound heterozygous ACBD5 mutations, presenting with the common features of rod monochromatism and progressive leukodystrophy with spasticity and ataxia. Additional novel clinical features included head and neck tremor and ovarian insufficiency. The patient's symptoms were present since infancy, but a diagnosis was only reached in adulthood when whole exome sequencing was performed. This case, which reports two novel mutations and additional clinical manifestations, contributes to the emerging phenotype of ACBD5-related retinal dystrophy with leukodystrophy, and delineation of the natural history and disease progression.
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Insuficiencia Ovárica Primaria , Distrofias Retinianas , Femenino , Humanos , Mutación , Linaje , Distrofias Retinianas/diagnóstico , Distrofias Retinianas/genética , Distrofias Retinianas/metabolismo , Fenotipo , Insuficiencia Ovárica Primaria/diagnóstico , Insuficiencia Ovárica Primaria/genética , Ataxia , Proteínas de la Membrana/genética , Proteínas Adaptadoras Transductoras de Señales/genéticaRESUMEN
Premature ovarian insufficiency (POI) is a condition in which there is a decline in ovarian function in women who are younger than 40 years resulting in a hypo-oestrogenic state with elevated gonadotrophins and oligomenorrhoea/amenorrhoea. This leads to short term complications of menopausal symptoms and long-term effects on bone and cardiovascular health, cognition as well as the impact of reduced fertility and sexual function associated with this condition. It is managed by sex steroid replacement either with HRT or combined hormonal contraception until the age of natural menopause (51) and this can provide a beneficial role with both symptom control and minimising the long-term adverse effects associated with this condition. Women who undergo a menopause between 40 and 45 years are deemed to have an "early menopause". The limited data available for this group suggest that they also have an increased morbidity if not adequately treated with hormone therapy. As such, women who have an early menopause should be managed in a similar way to those with POI, with the recommendation that they should take HRT at least until the natural age of menopause. This is the same for induced menopause that is caused by medical or surgical treatment that impacts the ovaries. It is important to ensure early diagnosis and access to specialist care to help support and manage these patients to reduce the symptoms and risks of long-term complications. This review looks at the diagnosis, causes, short and long-term complications and management of POI, early and induced menopause.
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Menopausia Prematura , Insuficiencia Ovárica Primaria , Humanos , Femenino , Insuficiencia Ovárica Primaria/etiología , Insuficiencia Ovárica Primaria/terapia , Insuficiencia Ovárica Primaria/diagnóstico , Menopausia , Amenorrea/etiologíaRESUMEN
STUDY QUESTION: Is it possible to find the cause of primary ovarian insufficiency (POI) in more women by extensive screening? SUMMARY ANSWER: Adding next generation sequencing techniques including a POI-associated gene panel, extended whole exome sequencing data, as well as specific autoantibody assays to the recommended diagnostic investigations increased the determination of a potential etiological diagnosis of POI from 11% to 41%. WHAT IS KNOWN ALREADY: POI affects â¼1% of women. Clinical presentations and pathogenic mechanisms are heterogeneous and include genetic, autoimmune, and environmental factors, but the underlying etiology remains unknown in the majority of cases. STUDY DESIGN, SIZE, DURATION: Prospective cross-sectional study of 100 women with newly diagnosed POI of unknown cause consecutively referred to Haukeland University Hospital, Bergen, Norway, January 2019 to December 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS: In addition to standard recommended diagnostic investigations including screening for chromosomal anomalies and premutations in the fragile X mental retardation 1 gene (FMR1) we used whole exome sequencing, including targeted analysis of 103 ovarian-related genes, and assays of autoantibodies against steroid cell antigens. MAIN RESULTS AND THE ROLE OF CHANCE: We identified chromosomal aberrations in 8%, FMR1 premutations in 3%, genetic variants related to POI in 16%, and autoimmune POI in 3%. Furthermore in 11% we identified POI associated genetic Variants of unknown signifcance (VUS). A homozygous pathogenic variant in the ZSWIM7 gene (NM_001042697.2) was found in two women, corroborating this as a novel cause of monogenic POI. No associations between phenotypes and genotypes were found. LIMITATIONS, REASONS FOR CAUTION: Use of candidate genetic and autoimmune markers limit the possibility to discover new markers. To further investigate the genetic variants, family studies would have been useful. We found a relatively high proportion of genetic variants in women from Africa and lack of genetic diversity in the genomic databases can impact diagnostic accuracy. WIDER IMPLICATIONS OF THE FINDINGS: Since no specific clinical or biochemical markers predicted the underlying cause of POI discussion of which tests should be part of diagnostic screening in clinical practice remains open. New technology has altered the availability and effectiveness of genetic testing, and cost-effectiveness analyses are required to aid sustainable diagnostics. STUDY FUNDING/COMPETING INTEREST(S): The study was supported by grants and fellowships from Stiftelsen Kristian Gerhard Jebsen, the Novonordisk Foundation, the Norwegian Research Council, University of Bergen, and the Regional Health Authorities of Western Norway. The authors declare no conflict of interest. TRIAL REGISTRATION NUMBER: NCT04082169.
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Insuficiencia Ovárica Primaria , Humanos , Femenino , Insuficiencia Ovárica Primaria/diagnóstico , Insuficiencia Ovárica Primaria/genética , Mutación , Estudios Transversales , Autoanticuerpos , Estudios Prospectivos , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/genéticaRESUMEN
Primary ovarian insufficiency (sometimes known as premature ovarian insufficiency) is a result of loss of ovarian follicular activity before the age of 40 years. It is an endocrine deficiency state in women, characterized by premature estrogen deprivation. In the absence of estrogen replacement, women experience bothersome menopause symptoms and a predisposition to accelerated aging and multimorbidity accumulation. Unless a true contraindication exists, estrogen therapy is recommended at least until the age of natural menopause. This Practice Pearl summarizes the clinical manifestations, diagnostic evaluation, and management of primary ovarian insufficiency.
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Menopausia Prematura , Insuficiencia Ovárica Primaria , Femenino , Humanos , Adulto , Insuficiencia Ovárica Primaria/diagnóstico , Insuficiencia Ovárica Primaria/genética , Insuficiencia Ovárica Primaria/tratamiento farmacológico , Terapia de Reemplazo de Estrógeno , Menopausia , Estrógenos/uso terapéuticoRESUMEN
PURPOSE: To investigate the skeletal phenotype of adolescent girls with premature ovarian insufficiency (POI). METHODS: Data are presented from two adolescent girls who participated in a clinical research protocol to evaluate axial bone mineral density (BMD) (via dual-energy x-ray absorptiometry, DXA) and appendicular bone density, microarchitecture, and strength (via high-resolution peripheral quantitative computed tomography, HRpQCT). Anthropometric data were also obtained, and pubertal staging was performed by a clinician. RESULTS: Both cases presented with an undetectable estradiol concentration and an elevated follicle stimulating hormone (FSH), meeting the criteria for POI. Each also received alkylating agents as part of their chemotherapy and radiotherapy, but in different locations as one presented with stage IV neuroblastoma and the other, metastatic medulloblastoma. Both had a low BMD of the axial and appendicular skeleton, as well as microarchitectural changes of the latter. The low BMD Z-score (<-2.0) seen when interpreting their DXA measurements for chronological age improved when adjusted for short stature, but it was not normalized. Lastly, most variables obtained by HRpQCT were abnormal for each participant, indicating that appendicular bone structure and strength were compromised. CONCLUSIONS: Chemotherapy and radiation affect growth, puberty, and bone accrual deleteriously. However, as these cases show, POI in an adolescent is not always classic primary ovarian insufficiency. Adolescents with brain cancer can present with signs of estrogen deficiency but may not be able to secrete FSH to the extent of elevation typically seen in long-term cancer survivors. Estrogen deficiency is almost universally present in either clinical setting and prompt recognition facilitates early provision of hormone replacement therapy that may then allow for a resumption of bone accrual as an adolescent approaches her peak bone mass.
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Supervivientes de Cáncer , Hipogonadismo , Neoplasias , Insuficiencia Ovárica Primaria , Humanos , Adolescente , Femenino , Densidad Ósea , Insuficiencia Ovárica Primaria/complicaciones , Insuficiencia Ovárica Primaria/diagnóstico , Absorciometría de Fotón , Hormona Folículo Estimulante , EstrógenosRESUMEN
BACKGROUND: Female survivors of childhood cancer are at risk for primary ovarian insufficiency (POI), defined as the cessation of gonadal function before the age of 40 years. We aimed to develop and validate models to predict age-specific POI risk among long-term survivors of childhood cancer. METHODS: To develop models to predict age-specific POI risk for the ages of 21-40 years, we used data from the Childhood Cancer Survivor Study (CCSS). Female survivors aged 18 years or older at their latest follow-up, with self-reported menstrual history information and free of subsequent malignant neoplasms within 5 years of diagnosis, were included. We evaluated models that used algorithms based on statistical or machine learning to consider all predictors, including cancer treatments. Cross-validated prediction performance metrics (eg, area under the receiver operating characteristic curve [AUROC]) were compared to select the best-performing models. For external validation of the models, we used data from 5-year survivors in the St Jude Lifetime Cohort (SJLIFE) with ovarian status clinically ascertained using hormone measurements (menopause defined by follicle stimulating hormone >30 mIU/mL and oestradiol <17 pg/mL) and medical chart or questionnaire review. We also evaluated an SJLIFE-based polygenic risk score for POI among 1985 CCSS survivors with genotype data available. FINDINGS: 7891 female CCSS survivors (922 with POI) were included in the development of the POI risk prediction model, and 1349 female SJLIFE survivors (101 with POI) were included in the validation study. Median follow-up from cancer diagnosis was 23·7 years (IQR 18·3-30·0) in CCSS and 15·1 years (10·4-22·9) in SJLIFE. Between the ages of 21 and 40 years, POI prevalence increased from 7·9% (95% CI 7·3-8·5) to 18·6% (17·3-20·0) in CCSS and 7·3% (5·8-8·9) to 14·9% (11·6-19·1) in SJLIFE. Age-specific logistic regression models considering ovarian radiation dosimetry or prescribed pelvic and abdominal radiation dose, along with individual chemotherapy predictors, performed well in CCSS. In the SJLIFE validation, the prescribed radiation dose model performed well (AUROC 0·88-0·95), as did a simpler model that considered any exposures to pelvic or abdominal radiotherapy or alkylators (0·82-0·90). Addition of the polygenic risk predictor significantly improved the average positive predictive value (from 0·76 [95% CI 0·63-0·89] to 0·87 [0·80-0·94]; p=0·029) among CCSS survivors treated with ovarian radiation and chemotherapy. INTERPRETATION: POI risk prediction models using treatment information showed robust prediction performance in adult survivors of childhood cancer. FUNDING: Canadian Institutes of Health Research, US National Cancer Institute.
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Supervivientes de Cáncer , Neoplasias , Insuficiencia Ovárica Primaria , Adulto , Humanos , Niño , Femenino , Adulto Joven , Neoplasias/terapia , Neoplasias/tratamiento farmacológico , Insuficiencia Ovárica Primaria/diagnóstico , Insuficiencia Ovárica Primaria/epidemiología , Insuficiencia Ovárica Primaria/etiología , Canadá , Sobrevivientes , Factores de Riesgo , Factores de EdadRESUMEN
La insuficiencia ovárica primaria es una condición en la que las mujeres menores de 40años experimentan oligomenorrea o amenorrea durante 4meses o más; esta pérdida temprana de la función ovárica puede estar relacionada con una serie de etiologías, incluidos trastornos genéticos, autoinmunes, infecciones o causas iatrogénicas; no obstante, del 74 al 90% son idiopáticas. A pesar de ser una alteración poco prevalente, es de gran importancia clínica, ya que afecta en múltiples aspectos de la vida a todas las mujeres. En la actualidad se están desarrollando diferentes estudios con el fin de encontrar nuevos blancos moleculares para establecer nuevas terapias para el tratamiento de esta patología.(AU)
Primary ovarian failure is a condition in which women under 40 experience oligomenorrhea or amenorrhea for 4months or longer; this early ovarian function loss may be related to a series of etiologies, including genetic disorders, autoimmune diseases, infections or iatrogenic causes; however 74%-90% are idiopathic. Despite being a less prevalent disorder, it is of great clinical importance since it affects all women in multiple aspects of life. At present, different studies are being developed in order to find new molecular targets to establish new therapies for the treatment of this pathology.(AU)