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This review summarises the present knowledge of prophylactic progesterone and preterm birth. Preterm birth (less-than 37 weeks) is a leading cause of neonatal mortality and morbidity worldwide. The incidence varies globally but remains low in the Nordic countries (5-6%). Prediction and prevention are complicated due to diverse aetiology, but obstetric history and cervical length can improve prediction. Prophylactic vaginal progesterone initiated between 12 and 24 weeks of gestation is recommended to reduce preterm birth less-than 33-35 weeks in singleton pregnancies with a history of preterm birth or with a short cervix (less-than 25 mm) and can be considered for twin pregnancies with the same risk factors.
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Nacimiento Prematuro , Progesterona , Progestinas , Humanos , Nacimiento Prematuro/prevención & control , Embarazo , Progesterona/administración & dosificación , Progesterona/uso terapéutico , Femenino , Progestinas/administración & dosificación , Progestinas/uso terapéutico , Administración Intravaginal , Factores de Riesgo , Medición de Longitud Cervical , Cuello del ÚteroRESUMEN
OBJECTIVE: To investigate the metabolic, cardiovascular, and neuropsychological phenotype, quality of life (QoL), and hormonal regulation in individuals with congenital adrenal hyperplasia (CAH), a group of autosomal recessive disorders characterized by impaired synthesis of cortisol in the adrenal cortex and, if untreated compensatory hyperandrogenism. CAH is associated with an increased cardiovascular and metabolic morbidity, possibly due to overtreatment with glucocorticoids, leading to weight gain, insulin resistance, and metabolic syndrome. DESIGN, PARTICIPANTS, MEASUREMENTS: Thirty-seven individuals with CAH and 33 age- and sex-matched controls were evaluated at a single centre at Aarhus University Hospital with echocardiography, electrocardiogram, 24-h blood pressure, biochemistry, anthropometrics, and autism spectrum, anxiety, depression, personality, cognitive failures, and QoL were assessed using questionnaires. RESULTS: CAH individuals had lower height than controls (170.5 vs. 182.9 cm in males and 160.2 vs. 170.1 cm in females, p < 0.01). Compared with female controls, females with CAH had higher haemoglobin (8.8 vs. 8.2 mmol/L, p = 0.003) and BMI (29.7 vs. 25.5 kg/m2, p = 0.006), reduced insulin sensitivity (HOMA-IR): 2.7 vs. 1.9, p = 0.018), prolonged E-wave deceleration time (193 vs. 174 cm, p = 0.015), and E/é ratios (5.4 vs. 4.5, p = 0.017), and lower self-reported QoL. Males with CAH had more cognitive complaints (p = 0.034) and higher autistic scores (19.9 vs. 14.9; p = 0.068) compared with male controls. More individuals with CAH than controls reported writing problems. CONCLUSION: A sex-specific comorbidity profile is evident in CAH, with females presenting with decreased metabolic and overall self-reported health, whereas males with CAH presented with increased cognitive complaints and autistic traits.
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Hiperplasia Suprarrenal Congénita , Calidad de Vida , Humanos , Hiperplasia Suprarrenal Congénita/psicología , Hiperplasia Suprarrenal Congénita/fisiopatología , Femenino , Masculino , Adulto , Persona de Mediana Edad , Adulto Joven , Estudios de Casos y ControlesRESUMEN
Sex chromosome abnormalities (SCAs) are chromosomal disorders with either a complete or partial loss or gain of sex chromosomes. The most frequent SCAs include Turner syndrome (45,X), Klinefelter syndrome (47,XXY), Trisomy X syndrome (47,XXX), and Double Y syndrome (47,XYY). The phenotype seen in SCAs is highly variable and may not merely be due to the direct genomic imbalance from altered sex chromosome gene dosage but also due to additive alterations in gene networks and regulatory pathways across the genome as well as individual genetic modifiers. This review summarizes the current insight into the genomics of SCAs. In addition, future directions of research that can contribute to decipher the genomics of SCA are discussed such as single-cell omics, spatial transcriptomics, system biology thinking, human-induced pluripotent stem cells, and animal models, and how these data may be combined to bridge the gap between genomics and the clinical phenotype.
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CONTEXT: Women with Turner syndrome (TS) suffer from hypergonadotropic hypogonadism, causing a deficit in gonadal hormone secretion. As a consequence, these women are treated with estrogen from the age of 12 years, and later in combination with progesterone. However, androgens have been given less attention. OBJECTIVE: To assess sex hormone levels in women with TS, both those treated and those nontreated with hormone replacement therapy (HRT), and investigate the impact of HRT on sex hormone levels. METHODS: At Aarhus University Hospital, 99 women with TS were followed 3 times from August 2003 to February 2010. Seventeen were lost during follow-up. Control group 1 consisted of 68 healthy age-matched control women seen once during this period. Control group 2 consisted of 28 young, eumenorrheic women sampled 9 times throughout the same menstrual cycle. Serum concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), 17ß-estradiol, estrone sulfate, DHEAS, testosterone, free androgen index, androstenedione, 17-OH progesterone, and sex hormone-binding globulin (SHBG) were analyzed. RESULTS: All androgens, 17-OH progesterone, and sex hormone-binding globulin (SHBG) were 30% to 50% lower in TS compared with controls (P < 0.01). FSH, LH, and estrone sulfate were more than doubled in women with TS compared with controls (P < 0.02). Using principal component analysis, we describe a positive correlation between women with TS receiving HRT, elevated levels of SHBG, and decreased levels of androgens. CONCLUSION: The sex hormone profile in TS reveals a picture of androgen deficiency, aggravated further by HRT. Conventional HRT does not normalize estradiol levels in TS.
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Andrógenos , Estrógenos , Terapia de Reemplazo de Hormonas , Síndrome de Turner , Andrógenos/deficiencia , Estradiol , Estrógenos/deficiencia , Femenino , Hormona Folículo Estimulante , Hormonas Esteroides Gonadales/uso terapéutico , Humanos , Hormona Luteinizante , Progesterona/uso terapéutico , Globulina de Unión a Hormona Sexual/análisis , Testosterona , Síndrome de Turner/tratamiento farmacológicoRESUMEN
The literature about eye, ear, nose, skin, and nervous system disorders in women with Turner syndrome is equivocal. Impaired vision and hearing in women with Turner syndrome have been described, and case reports of Turner syndrome girls suffering from epilepsy have been published, but no large population-based-studies have explored the occurrence of any of these disorders. We aimed to investigate the risk of admission with disorders related to the eye, ear, nose, skin, and nervous system, compared with background females, and the impact of hormone replacement therapy on these conditions. 1,156 females with TS diagnosed during 1960-2014 were identified using the Danish Cytogenetic Central Registry and linked with personal-level data from the National Patient Registry and the Medication Statistics Registry. Statistics Denmark randomly identified 115,577 age-matched background females. Negative binomial regression was used to analyze hospital discharge diagnoses, reporting incidence rate ratios (IRR). Women with Turner syndrome have an increased risk of developing eye disorders (IRR 4.3 (95% CI 3.5-5.4), including cataract, glaucoma, ocular movement, and accommodation. The risk of ear disorders (IRR 35.0 (27.9-43.9)) and nose (IRR 2.2 (1.4-3.6)) was increased in women with Turner syndrome, due to otitis media, cholesteatoma, and hearing loss. Disorders of the nervous system such as epilepsy were increased IRR 6.2 (2.4-15.9), along with skin conditions IRR 2.2 (95%CI 1.7-2.7) like psoriasis, atopic dermatitis, and ingrown nails.
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Síndrome de Turner , Estudios de Cohortes , Femenino , Humanos , Incidencia , Sistema Nervioso , Sistema de Registros , Síndrome de Turner/complicaciones , Síndrome de Turner/tratamiento farmacológico , Síndrome de Turner/epidemiologíaRESUMEN
BACKGROUND: Liver and gastrointestinal diseases are frequent in women with Turner syndrome. However, their association with bleeding disorders, anaemia and the impact of hormone replacement therapy is unknown. AIMS: To investigate the risk of liver and gastrointestinal diseases, haemorrhage and anaemia in women with Turner syndrome compared with the female background population, and the long-term impact of hormone replacement therapy on these conditions. METHODS: One thousand one hundred and fifty-six women with Turner syndrome diagnosed during 1960-2014 were identified using the Danish Cytogenetic Central Registry and linked with personal-level data from the National Patient Registry and the Medication Statistics Registry. Statistics Denmark randomly identified 115 577 age-matched female controls. Negative binomial regression was used to analyse hospital discharge diagnoses. Medical prescriptions, mortality and the effect of hormone replacement therapy were estimated using stratified Cox regression. RESULTS: Liver disease increased 13-fold (IRR 12.9 (95% CI 5.8-28.8)), due to toxic liver disease (IRR 8.0 (95% CI 1.8-35.4)), liver insufficiency (IRR 6.7 (95% CI 1.7-26.9)), fibrosis/cirrhosis (IRR 16.5 (95% CI 2.2-122.1)) and unspecified liver disease (IRR 10.6 (95% CI 4.4-25.3)). Furthermore, presence of abnormal liver enzymes increased 12-fold (IRR 12.4 (95% CI 4.2-36.6)). The risk of gastrointestinal haemorrhage (IRR 3.4 (95% CI 1.8-6.2)), anaemia (IRR 3.2 (95% CI 2.0-5.0)) and coagulation disorders (IRR 2.9 (95% CI 1.1-7.1)) was increased. However these diagnoses were not associated with inflammatory bowel disease. Gastrointestinal mortality was increased three-fold (HR 3.1 (95% CI 1.5-6.2)), partly due to death by liver disease (HR 3.0 (95% CI 1.1-8.2)), gastrointestinal haemorrhage (HR 29.6 (95% CI 3.1-285.1)) and capillary malformations (HR 18.6 (95% CI 4.1-85.0)). There was no effect of hormone replacement therapy on gastrointestinal risk but a trend towards a beneficial impact on liver diseases. CONCLUSIONS: The risk of being diagnosed with liver disease was higher than previously reported. The occurrence of gastrointestinal haemorrhage and anaemia was increased in Turner syndrome. There was no effect of hormone replacement therapy on gastrointestinal risk but a trend towards a beneficial impact on liver diseases was detected.
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Anemia , Enfermedades Gastrointestinales , Síndrome de Turner , Estudios de Cohortes , Dinamarca/epidemiología , Femenino , Enfermedades Gastrointestinales/epidemiología , Enfermedades Gastrointestinales/etiología , Humanos , Incidencia , Hígado , Síndrome de Turner/complicaciones , Síndrome de Turner/epidemiologíaRESUMEN
OBJECTIVE: Although the overall risk of cancer is not increased in Turner syndrome, the pattern of cancer occurrence differs from the general population. We aim to describe the cancer morbidity pattern in Turner syndrome and evaluate the effect of long-term hormone replacement therapy (HRT). DESIGN: Nationwide epidemiological study. METHODS: 1156 females with Turner syndrome diagnosed during 1960-2014, were linked with data from the Danish National Patient Registry. Statistics Denmark randomly identified 115 578 female controls. Stratified Cox regression was used to analyze cancer morbidity, mortality and effect of HRT. RESULTS: Overall risk of cancer was not elevated (hazard ratio 1.04 (95% CI: 0.80-1.36)). The risk of skin cancer and benign skin neoplasms was two-fold increased, while the risk of breast cancer was decreased (hazard ratio 0.4 (0.2-0.9)). Turner syndrome (45,X) had a two- to five-fold increased risk of benign CNS tumors, colon and rectal cancers, benign skin neoplasms and skin cancer. Turner syndrome women with a 45,X/46,XX karyotype had an increased risk of tongue cancer. HRT had no impact on the risk of any cancer investigated in this study. CONCLUSIONS: The lack of one X chromosome might play a role in skin neoplasms, CNS tumors, colon and rectal cancers. The risk of breast cancer is lower than in the general population. Long-term HRT during the premenopausal age range seems not to exert a cancerous effect in Turner syndrome. Increased vigilance concerning specific types of cancer in Tuner syndrome harboring a 45,X karyotype is needed.
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Hormonas Esteroides Gonadales/efectos adversos , Terapia de Reemplazo de Hormonas/efectos adversos , Neoplasias/epidemiología , Síndrome de Turner/complicaciones , Síndrome de Turner/tratamiento farmacológico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Dinamarca/epidemiología , Femenino , Hormonas Esteroides Gonadales/uso terapéutico , Humanos , Incidencia , Persona de Mediana Edad , Neoplasias/etiología , Prevalencia , Sistema de Registros , Riesgo , Aberraciones Cromosómicas Sexuales , Síndrome de Turner/epidemiología , Adulto JovenRESUMEN
BACKGROUND: Knowledge on the prevalence of sex chromosome abnormalities (SCAs) is limited, and delayed diagnosis or non-diagnosis of SCAs are a continuous concern. We aimed to investigate change over time in incidence, prevalence and age at diagnosis among Turner syndrome (TS), Klinefelter syndrome (KS), Triple X syndrome (Triple X) and Double Y syndrome (Double Y). METHODS: This study is a nationwide cohort study in a public health care system. The Danish Cytogenetic Central Registry (DCCR) holds information on all karyotypes performed in Denmark since 1961. We identified all individuals in the DCCR with a relevant SCA during 1961-2014; TS: n = 1156; KS: n = 1235; Triple X: n = 197; and Double Y: n = 287. From Statistics Denmark, which holds an extensive collection of data on the Danish population, complete data concerning dates of death and migrations in and out of Denmark were retrieved for all individuals. RESULTS: The prevalence among newborns was as follows: TS: 59 per 100,000 females; KS: 57 per 100,000 males; Triple X: 11 per 100,000 females; and Double Y: 18 per 100,000 males. Compared with the expected number among newborns, all TS, 38% of KS, 13% of Triple X, and 18% of Double Y did eventually receive a diagnosis. The incidence of TS with other karyotypes than 45,X (P < 0.0001), KS (P = 0.02), and Double Y (P = 0.03) increased during the study period whereas the incidence of 45,X TS decreased (P = 0.0006). The incidence of Triple X was stable (P = 0.22). CONCLUSIONS: The prevalence of TS is higher than previously identified, and the karyotypic composition of the TS population is changing. Non-diagnosis is extensive among KS, Triple X and Double Y, whereas all TS seem to become diagnosed. The diagnostic activity has increased among TS with other karyotypes than 45,X as well as among KS and Double Y.
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Síndrome de Turner/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Cromosomas Humanos X/genética , Estudios de Cohortes , Femenino , Humanos , Incidencia , Lactante , Recién Nacido , Cariotipificación , Síndrome de Klinefelter/genética , Masculino , Persona de Mediana Edad , Aberraciones Cromosómicas Sexuales , Trastornos de los Cromosomas Sexuales/genética , Trastornos de los Cromosomas Sexuales del Desarrollo Sexual/genética , Trisomía/genética , Cariotipo XYY/genética , Adulto JovenRESUMEN
STUDY QUESTION: How does a national prenatal screening program for Down syndrome (DS) perform in detecting sex chromosome abnormalities (SCAs)-Turner syndrome (TS), Klinefelter syndrome, 47,XXX and 47,XYY syndromes. SUMMARY ANSWER: The SCA detection rate resulting from DS screening was below 50% for all four groups of SCAs. WHAT IS KNOWN ALREADY: The detection rates of SCAs are higher in countries with DS screening. TS is associated with greater nuchal translucency (NT) and lower pregnancy-associated plasma protein-A (PAPP-A). However, specific detection rates of SCAs using prenatal DS screening have not been determined. No clear trend in PAPP-A, free beta human chorionic gonadotropin (ß-hCG) and NT has been found in the remaining SCAs. Several lines of inquiry suggest that it would be advantageous for individuals with SCA to be detected early in life, leading to prevention or treatment of accompanying conditions. There is limited information about pre- and perinatal status that distinguishes SCA embryogenesis from normal fetal development. STUDY DESIGN, SIZE, DURATION: A register-based case-control study from the Danish Central Cytogenetic Register (DCCR), cross-linked with the Danish Fetal Medicine Database (DFMD), was performed from 2008 to 2012. Groups of SCAs were compared with DS and then matched with non-SCA controls to assess differences between these groups in prenatal markers and birth outcomes. PARTICIPANTS/MATERIALS, SETTING, METHODS: We included cases with prenatal and post-natal SCA karyotypes (n = 213), DS (n = 802) and 168 056 controls. We screened 275 037 individuals examined prenatally. We retrieved information regarding maternal age, NT, ß-hCG and PAPP-A, as well as details regarding maternal and newborn characteristics. MAIN RESULTS AND THE ROLE OF CHANCE: The DS screening procedure detected 87 per 100 000 TS (42% of expected), 19 per 100 000 Klinefelter syndrome (13% of expected), 16 per 100 000 47,XXX (16% of cases) and 5 per 100 000 47,XYY (5% of expected) SCAs, with an overall detection rate of 27%. Compared with controls, all four SCA groups showed significantly higher NT and lower PAPP-A compared with controls (all P < 0.01) and similar to DS. The legal abortion rate was high for all four syndromes (47,XXX: 24%; 47,XYY: 29%; Klinefelter syndrome: 48%, TS: 84%). For SCA fetuses carried to term, only TS fetuses had consistently lower birthweights and placenta weights than non-SCA controls (both P = 0.0001). A few SCA cases localized in DCCR could not be found in DFMD (n = 16). LIMITATIONS, REASON FOR CAUTION: Controls were matched on sex of the fetus of cases, meaning that all electively aborted fetuses (before week 12) were excluded, possibly reducing the diversity in the control group. We were not able to localize all diagnosed cases of SCA and DS in DFMD. Although these cases were present in DCCR, we were not able to account for the discrepancy. In addition, we suspect that several SCA children have not been diagnosed yet and future post-natal diagnosis of these cases would reduce the diagnostic yield reported here even further. WIDER IMPLICATIONS OF THE FINDINGS: The prenatal detection rate is below 50% for all SCAs. The approach used for detecting DS cannot be extended to also include SCAs. In addition, all SCAs have low PAPP-A and increased NT, thus probably reflecting an abnormal embryogenesis. Growth retardation of TS fetuses is if anything more pronounced than previously reported, both when evaluating fetus and placenta. STUDY FUNDING/COMPETING INTERESTS: This study received support from Aarhus University and the Novo Nordisk Foundation. The authors have no competing interests that may be relevant to the study.