RESUMEN
STUDY OBJECTIVE: To determine the metabolic effects of the subcutaneous etonogestrel implant compared with an oral contraceptive in adolescents and young adults (AYAs) with type 1 diabetes (T1D) on body weight, body composition, glucose, lipids, and C-reactive protein levels. METHODS: This was a non-randomized, interventional, prospective study. Thirty-nine AYAs with T1D participated; 20 used the implant (Implant-T1D), and 19 used an oral combined contraceptive (OC-T1D). Body composition, HbA1c, intermittent continuous glucose monitoring, lipids, and high-sensitivity C-reactive protein (hsCRP) levels were evaluated. RESULTS: All participants were followed for at least 12 months, and 26 completed the 24-month follow-up. No women discontinued the intervention due to adverse effects. Body weight increased by 0.8 ± 3.5 and 1 ± 2.9 kg in the OC-T1D and the Implant-T1D group at 12 months and by 2.6 ± 3.9 and 3.3 ± 3.6 kg at 24 months, respectively. OC-T1D and Implant-T1D had similar HbA1c, mean interstitial glucose levels, and time in range throughout the study; no significant difference over time was observed. hsCRP levels increased in both groups and were associated with BMI and HbA1c (P < .001 for both variables). Women in the OC-T1D group had higher total cholesterol, HDL-C, and triglyceride levels compared with the Implant-T1D. CONCLUSION: Glucose levels were similar in youth using the subdermal progestin implant and an OC. However, both AYA groups showed increased BMI, fat mass, and subclinical inflammation. Changes in lipid levels were associated with the OC method. These data highlight the importance of weight gain prevention in young women with T1D using hormonal contraception.
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Anticonceptivos Orales , Diabetes Mellitus Tipo 1 , Adulto Joven , Femenino , Adolescente , Humanos , Progestinas , Proteína C-Reactiva , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Hemoglobina Glucada , Estudios Prospectivos , Automonitorización de la Glucosa Sanguínea , Glucemia , Peso Corporal , LípidosRESUMEN
CONTEXT: The melanocortin 3 receptor (MC3R) has recently emerged as a critical regulator of pubertal timing, linear growth, and the acquisition of lean mass in humans and mice. In population-based studies, heterozygous carriers of deleterious variants in MC3R report a later onset of puberty than noncarriers. However, the frequency of such variants in patients who present with clinical disorders of pubertal development is currently unknown. OBJECTIVE: This work aimed to determine whether deleterious MC3R variants are more frequently found in patients clinically presenting with constitutional delay of growth and puberty (CDGP) or normosmic idiopathic hypogonadotropic hypogonadism (nIHH). METHODS: We examined the sequence of MC3R in 362 adolescents with a clinical diagnosis of CDGP and 657 patients with nIHH, experimentally characterized the signaling properties of all nonsynonymous variants found and compared their frequency to that in 5774 controls from a population-based cohort. Additionally, we established the relative frequency of predicted deleterious variants in individuals with self-reported delayed vs normally timed menarche/voice-breaking in the UK Biobank cohort. RESULTS: MC3R loss-of-function variants were infrequent but overrepresented in patients with CDGP (8/362 [2.2%]; OR = 4.17; P = .001). There was no strong evidence of overrepresentation in patients with nIHH (4/657 [0.6%]; OR = 1.15; P = .779). In 246 328 women from the UK Biobank, predicted deleterious variants were more frequently found in those self-reporting delayed (aged ≥16 years) vs normal age at menarche (OR = 1.66; P = 3.90E-07). CONCLUSION: We have found evidence that functionally damaging variants in MC3R are overrepresented in individuals with CDGP but are not a common cause of this phenotype.
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Hipogonadismo , Pubertad Tardía , Adolescente , Humanos , Femenino , Animales , Ratones , Receptor de Melanocortina Tipo 3 , Prevalencia , Hipogonadismo/epidemiología , Hipogonadismo/genética , Hipogonadismo/complicaciones , Pubertad Tardía/epidemiología , Pubertad Tardía/genética , Pubertad Tardía/diagnóstico , Pubertad/genética , Trastornos del Crecimiento/genéticaRESUMEN
BACKGROUND: Infantile hemangiomas are vascular anomalies. However, they rarely cause genital bleeding. Here, we present the case of a young female with an endocavitary hemangioma who presented with abnormal uterine bleeding (AUB). CASE: The patient was an 8-year-old female with genital bleeding. Transabdominal pelvic ultrasound showed a 20-mm highly vascularized focal intrauterine endocavitary lesion. Vascular computerized tomography excluded vascular anomalies. Magnetic resonance imaging suggested a hemangioma. Minimally invasive open surgery was performed to remove the lesion. Subsequent pathology analyses confirmed an infantile/capillary hemangioma. CONCLUSIONS: Infantile hemangiomas are vascular anomalies that should be considered potential causes of AUB in early puberty. The study of these cases should include pelvic ultrasound and vascular magnetic resonance imaging. Experienced surgeons can successfully accomplish fertility-sparing surgical procedures. SUMMARY: We describe an unusual case of peripubertal AUB caused by an endocavitary capillary hemangioma. Management included fertility-sparing surgery and the complete resolution of symptoms.
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Hemangioma Capilar , Hemangioma , Malformaciones Vasculares , Niño , Femenino , Genitales , Hemangioma/complicaciones , Hemangioma/diagnóstico por imagen , Hemangioma/cirugía , Hemangioma Capilar/complicaciones , Hemangioma Capilar/diagnóstico por imagen , Hemangioma Capilar/cirugía , Hemorragia , HumanosRESUMEN
PURPOSE OF REVIEW: This article reviews how to address contraception in young women with type 2 diabetes (T2D). The presence of obesity and comorbidities associated with insulin resistance increases the risk of thromboembolic disease and adverse cardiovascular outcomes. RECENT FINDINGS: Recent studies have shown that adolescents with T2D are at high risk of unintended pregnancy with poor outcomes for the mother and offspring. Adolescents with T2D without severe obesity, micro- or macrovascular disease, or other cardiovascular risk factors can use any contraceptive method. However, only nonhormonal or progestin-only methods may be used when morbid obesity, severe hypertension, micro- or macrovascular disease, or multiple cardiovascular risk factors are present. The medical team must provide preconceptional counseling and contraception to reduce adolescent pregnancies in young women with T2D. Progestin-only or nonhormonal long-acting reversible contraception (LARC) should be recommended for women with T2D with compliance issues or adverse cardiovascular risk profiles.
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Diabetes Mellitus Tipo 2 , Anticoncepción Reversible de Larga Duración , Adolescente , Anticoncepción/métodos , Diabetes Mellitus Tipo 2/epidemiología , Femenino , Humanos , Embarazo , Embarazo no Planeado , ProgestinasRESUMEN
CONTEXT: An association between premature adrenarche and metabolic syndrome at presentation has been described. Our aim was to assess whether the presence of high dehydroepiandrosterone sulphate (DHEAS [HD]) at the adrenarche determines the risk of metabolic syndrome during puberty, taking into account body mass index (BMI) and birth weight. DESIGN: Prospective observational. PATIENTS: Five hundred four girls from the Growth and Obesity Chilean Cohort Study were followed from birth through puberty. At age ~7, subjects were classified by DHEAS concentrations into the HD (>75th percentile) or normal DHEAS (ND, ≤75th percentile) subgroups. MEASUREMENTS: Anthropometrics, semiannual clinical pubertal staging and hormonal and metabolic levels. The relationships among DHEAS at age ~7, metabolic syndrome, and each of its components independently, were analyzed by linear and logistic regression models during puberty and 1-year postmenarche, adjusted by confounders. RESULTS: Girls with HD at 7 years exhibited higher BMI, more central fat and higher serum androgen and insulin like growth factor (IGF)-I levels throughout puberty. Also, girls with HD had a greater prevalence of hyperglycemia at B2 and B4 breast stages, and of low HDL at B4. At 1 year after menarche, HD girls had a higher prevalence of metabolic syndrome, and those with BMI > 1 SD score had a higher metabolic score and insulin levels than ND girls with similar BMI. CONCLUSIONS: Our observations suggest that girls with HD at the age of adrenarche may be at greater risk for metabolic syndrome at adolescence, especially in those who are overweight or obese. Our results emphasize the importance of lifestyle interventions for childhood overweight and obesity among girls with HD.
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Adrenarquia , Síndrome Metabólico , Adolescente , Índice de Masa Corporal , Niño , Estudios de Cohortes , Deshidroepiandrosterona , Sulfato de Deshidroepiandrosterona , Femenino , Humanos , Masculino , Obesidad , PubertadRESUMEN
PURPOSE: SOX10 variants previously implicated in Waardenburg syndrome (WS) have now been linked to Kallmann syndrome (KS), the anosmic form of idiopathic hypogonadotropic hypogonadism (IHH). We investigated whether SOX10-associated WS and IHH represent elements of a phenotypic continuum within a unifying disorder or if they represent phenotypically distinct allelic disorders. METHODS: Exome sequencing from 1,309 IHH subjects (KS: 632; normosmic idiopathic hypogonadotropic hypogonadism [nIIHH]: 677) were reviewed for SOX10 rare sequence variants (RSVs). The genotypic and phenotypic spectrum of SOX10-related IHH (this study and literature) and SOX10-related WS cases (literature) were reviewed and compared with SOX10-RSV spectrum in gnomAD population. RESULTS: Thirty-seven SOX10-associated IHH cases were identified as follows: current study: 16 KS; 4 nIHH; literature: 16 KS; 1 nIHH. Twenty-three IHH cases (62%; all KS), had ≥1 known WS-associated feature(s). Moreover, five previously reported SOX10-associated WS cases showed IHH-related features. Four SOX10 missense RSVs showed allelic overlap between IHH-ascertained and WS-ascertained cases. The SOX10-HMG domain showed an enrichment of RSVs in disease states versus gnomAD. CONCLUSION: SOX10 variants contribute to both anosmic (KS) and normosmic (nIHH) forms of IHH. IHH and WS represent SOX10-associated developmental defects that lie along a unifying phenotypic continuum. The SOX10-HMG domain is critical for the pathogenesis of SOX10-related human disorders.
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Hipogonadismo , Síndrome de Kallmann , Factores de Transcripción SOXE/genética , Síndrome de Waardenburg , Genotipo , Humanos , Hipogonadismo/genética , Mutación , Síndrome de Waardenburg/genéticaRESUMEN
CONTEXT: Functional hypothalamic amenorrhea (HA) is a common, acquired form of hypogonadotropic hypogonadism that occurs in the setting of energy deficits and/or stress. Variability in individual susceptibility to these stressors, HA heritability, and previous identification of several rare sequence variants (RSVs) in genes associated with the rare disorder, isolated hypogonadotropic hypogonadism (IHH), in individuals with HA suggest a possible genetic contribution to HA susceptibility. OBJECTIVE: We sought to determine whether the burden of RSVs in IHH-related genes is greater in women with HA than controls. DESIGN: We compared patients with HA to control women. SETTING: The study was conducted at secondary referral centers. PATIENTS AND OTHER PARTICIPANTS: Women with HA (nâ =â 106) and control women (ClinSeq study; nâ =â 468). INTERVENTIONS: We performed exome sequencing in all patients and controls. MAIN OUTCOME MEASURE(S): The frequency of RSVs in 53 IHH-associated genes was determined using rare variant burden and association tests. RESULTS: RSVs were overrepresented in women with HA compared with controls (Pâ =â .007). Seventy-eight heterozygous RSVs in 33 genes were identified in 58 women with HA (36.8% of alleles) compared to 255 RSVs in 41 genes among 200 control women (27.2%). CONCLUSIONS: Women with HA are enriched for RSVs in genes that cause IHH, suggesting that variation in genes associated with gonadotropin-releasing hormone neuronal ontogeny and function may be a major determinant of individual susceptibility to developing HA in the face of diet, exercise, and/or stress.
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Amenorrea/genética , Hormona Liberadora de Gonadotropina/metabolismo , Enfermedades Hipotalámicas/genética , Adolescente , Adulto , Anciano , Amenorrea/epidemiología , Amenorrea/etiología , Estudios de Casos y Controles , Niño , Análisis Mutacional de ADN , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Hipogonadismo/epidemiología , Hipogonadismo/etiología , Hipogonadismo/genética , Enfermedades Hipotalámicas/complicaciones , Enfermedades Hipotalámicas/epidemiología , Redes y Vías Metabólicas/genética , Persona de Mediana Edad , Mutación Missense , Secuenciación del Exoma , Adulto JovenRESUMEN
Adolescent pregnancy is a major public health problem worldwide. Adolescents living with diabetes are not aware of the risks of unplanned pregnancy and the high rate of fetal and maternal complications when gestation occurs in women with significant hyperglycemia. These data highlight the significance of pregnancy prevention in young women with diabetes. Long-acting reversible contraceptives (LARCs), which include subdermal progestin implants and hormonal and nonhormonal intrauterine devices (IUDs), have been recommended by the American College of Obstetricians Gynecologists and the American Academy of Pediatrics as a first-line contraceptive option for adolescents and young women. This article reviews LARC options for adolescents and young women with type 1 (T1D) and type 2 (T2D) diabetes as well as the possible complications and side effects.
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Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Anticoncepción Reversible de Larga Duración , Adolescente , Efectividad Anticonceptiva , Femenino , Humanos , Embarazo , Adulto JovenRESUMEN
STUDY OBJECTIVE: To assess pubertal events in a Hispanic female population and to create normograms of puberty. DESIGN: Longitudinal. SETTING: University facility. PARTICIPANTS: Five hundred forty-nine girls from the Growth and Obesity Chilean Cohort study. INTERVENTIONS: Follow-up twice a year beginning at age 6 years. MAIN OUTCOME MEASURES: Breast development, pubic hair development, and age. Breast development (B2, B3, and B4) and pubarche (P2) were determined. Age at menarche was obtained from the adolescents and their mothers. Age and growth velocity at peak height velocity were calculated. RESULTS: In girls, B2, B3, and B4 occur at median ages of 9.2, 10.2, and 10.9 years, respectively. The median age at P2 was 9.7 years. The mean age at peak height velocity and the growth velocity were 10.6 years (SD = 1.1) and 8 cm/y, respectively. The mean age at menarche was 11.9 years (SD = 1.1); only 2.8% (15 /530) of girls experienced menarche after 14 years and 1.9% before 10 years. The mean interval time between B2 and menarche was 2.5 ± 1.0 years. Transient thelarche occurred in 8.6% of girls. CONCLUSION: This longitudinal cohort shows that thelarche occurred 1.2 months later than previously reported in cross-sectional studies. Conversely, we found that pubic hair appeared 12 months earlier and menarche occurred 9 months earlier than previously reported. These findings are important in setting normalcy data and avoiding unnecessary clinical consultations.
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Factores de Edad , Hispánicos o Latinos/estadística & datos numéricos , Menarquia , Pubertad , Adolescente , Niño , Chile , Estudios de Cohortes , Estudios Transversales , Femenino , Humanos , Estudios Longitudinales , Obesidad/fisiopatología , Maduración SexualRESUMEN
OBJECTIVE: To assess whether the presence of high DHEAS (HD) at 7 years determines different timing, sequence, and rate of pubertal events, and whether it is associated with adrenal and/or ovarian hyperandrogenism and changes in ovarian morphology throughout puberty. METHODS: In a longitudinal study of 504 girls, clinical evaluation was performed every 6 months after 7 years of age to detect Tanner stages; hormonal and anthropometric measurements were conducted at thelarche (B2), breast Tanner 4 (B4), and 1 year after menarche; ultrasonographic evaluation was also performed after menarche. The girls were classified as HD if their DHEAS level was >42.1 µg/dL (>75th percentile) around 7 years. RESULTS: HD around 7 years is associated with a younger age at thelarche, pubarche, and menarche. Girls with HD had higher androstenedione and total testosterone levels, and a higher free androgen index (FAI), and lower levels of antimüllerian hormone (AMH) at B2, and higher levels of androstenedione and FAI at B4 and after menarche. All these results were significant even after adjusting for body mass index, age at first DHEAS determination, and birth weight. One year after menarche, polycystic ovarian morphology was detected in 7.6 and 7.3% of the HD and the normal DHEAS group, respectively. Ovarian volume was correlated with AMH, testosterone, androstenedione, and LH but not with DHEAS around 7 years. CONCLUSION: Prepubertal HD in normal girls was associated with earlier thelarche, pubarche, and menarche, and a mild androgen increase throughout puberty. We believe continuous follow-up of this cohort is important to prospectively address the interrelationships between biochemical adrenarche and early growth as determinants of ovarian function.
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Adrenarquia/sangre , Andrógenos/sangre , Sulfato de Deshidroepiandrosterona/sangre , Ovario , Pubertad Precoz , Adolescente , Niño , Preescolar , Estudios Transversales , Femenino , Estudios de Seguimiento , Humanos , Estudios Longitudinales , Ovario/metabolismo , Ovario/patología , Pubertad Precoz/sangre , Pubertad Precoz/patologíaRESUMEN
STUDY OBJECTIVE: To compare ovarian function between adolescents conceived using assisted reproductive technology (AcART) and adolescents who were conceived spontaneously (AcSP). DESIGN: Multicenter study of ovarian function in AcART because of male or tubal infertility. SETTING: University Hospital. PARTICIPANTS: We evaluated 22 AcART and 53 AcSP at 1-2 years after menarche. The participants were born at term (≥37 weeks of gestation) with normal birth weights (≥2500 g) from singleton pregnancies. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Differences in ovulation, reproductive hormones, and ovarian morphology. RESULTS: AcART had an older age of menarche than that of AcSP, even after adjusting for maternal age at menarche, gestational age, and birth weight (P = .027). AcART had lower incidence of ovulation (P = .021) and higher luteinizing hormone serum levels (P = .01) than those of AcSP. The incidence of oligomenorrhea and the cycle length were similar between AcART and AcSP. AcART had levels of anti-Müllerian hormone, inhibin B, follicle-stimulating hormone, estradiol, and androgens similar to those of AcSP. The ovarian morphology, ovarian volume, and follicle counts were similar in both groups. CONCLUSION: AcART had later menarche, lower ovulation rates, and higher luteinizing hormone levels than those of AcSP. Future studies should investigate whether these findings are indicative of a risk of ovarian dysfunction later in life for AcART.
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Ovario/fisiología , Ovulación/fisiología , Técnicas Reproductivas Asistidas/efectos adversos , Adolescente , Femenino , Hormonas Gonadales/sangre , Gonadotropinas/sangre , Humanos , Embarazo , Embarazo en Adolescencia/fisiología , Globulina de Unión a Hormona Sexual/análisis , UltrasonografíaRESUMEN
Context: Hypothalamic kisspeptin signaling plays a critical role in the initiation and maintenance of reproductive function. Biallelic mutations in the coding sequence of KISS1R (GPR54) have been identified in patients with idiopathic hypogonadotropic hypogonadism, but it is unknown whether biallelic variants can also be associated with related reproductive disorders. Case Description: A missense homozygous variant (c.890G>T p.R297L) in KISS1R was identified in a child who presented with microphallus and bilateral cryptorchidism. This variant has been reported to reduce, but not abolish, postreceptor signaling in vitro. Biochemical evaluation during the neonatal period revealed low testosterone levels. By 11 years and 8 months, the boy began demonstrating increases in testicular volume. By 17 years and 3 months, his testicular volume was 20 mL; his penile length was 7.3 cm; and he had adult levels of circulating gonadotropins and testosterone. Conclusion: This case report associates biallelic loss-of-function mutations in KISS1R with normal timing of adolescent puberty. Because these coding sequence variants occurred in a patient with microphallus and cryptorchidism, they demonstrate different levels of dependence of the hypothalamic-pituitary-gonadal cascade on kisspeptin signaling at distinct times in the reproductive life span. The suppression of the hypothalamic-pituitary-gonadal cascade during early life but not adolescence suggests that the mini puberty of infancy depends more on kisspeptin-induced, gonadotropin-releasing hormone-induced luteinizing hormone secretion than does adolescent puberty.
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Criptorquidismo/genética , Kisspeptinas/fisiología , Receptores de Kisspeptina-1/genética , Maduración Sexual/genética , Criptorquidismo/sangre , Criptorquidismo/fisiopatología , Hormona Folículo Estimulante/sangre , Estudios de Seguimiento , Humanos , Lactante , Hormona Luteinizante/sangre , Masculino , Mutación Missense , Pene/anomalías , Maduración Sexual/fisiología , Transducción de Señal/genética , Transducción de Señal/fisiología , Testosterona/sangreRESUMEN
BACKGROUND: The ultrasonographic criteria used to identify polycystic ovarian morphology (PCOM) during adolescence have changed over time. Recently, a Worldwide Pediatric Consensus (PedC) defined PCOM using stricter criteria than the previous recommendations of the Rotterdam Consensus (RC) and Androgen Excess-Polycystic Ovarian Syndrome Society (AES/PCOS) criteria. The aim of this study was to determine the prevalence of PCOM in healthy adolescents according to the 3 reported diagnostic criteria and compare the hormonal profile in females with and without PCOM based on the PedC criteria. METHODS: Nonobese adolescents (n = 102) with regular menstrual cycles were studied. Transabdominal ultrasound and hormonal profiles were assessed during the follicular phase. PCOM was defined on the basis of the 3 published criteria. RESULTS: On the basis of the PedC, RC, and AES/PCOS criteria, PCOM was diagnosed in 13, 34, and 24% of adolescents, respectively. Adolescents with and without PCOM according to the PedC criteria had similar androgen levels. Serum anti-Müllerian hormone (AMH) levels were elevated in adolescents with PCOM, irrespective of the criteria used. CONCLUSIONS: Use of the new PedC diagnostic criteria for PCOM results in a lower prevalence of this ultrasonographic pattern in adolescents, but this condition is not associated with hyperandrogenism. Elevated AMH is associated with PCOM in adolescents regardless of the criteria used to determine the ultrasonographic pattern.
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Andrógenos/sangre , Síndrome del Ovario Poliquístico/sangre , Síndrome del Ovario Poliquístico/diagnóstico por imagen , Síndrome del Ovario Poliquístico/epidemiología , Adolescente , Adulto , Estudios Transversales , Femenino , Humanos , Prevalencia , UltrasonografíaRESUMEN
We evaluated the association of hirsutism and oligomenorrhea (persistent menstrual cycles > 45 days) as screening criteria for the detection of biochemical hyperandrogenism (BH) and polycystic ovaries (PCOM) during adolescence and determined which androgens, granulosa cell hormone, ultrasonographic parameters have the best association with polycystic ovary syndrome (PCOS). Hirsute girls with oligomenorrhea (N = 26 Hirs/Oligo group) and non-hirsute girls with regular cycles (N = 63, C group) were studied. Prevalence of BH and PCOM, diagnostic performance of androgens and ultrasound parameters for PCOS diagnosis were analyzed. BH and PCOM prevalence were higher in the Hirs/Oligo girls than in the C girls (76.9% versus 25.5%; 92.3% versus 33.3%, respectively; p < 0.0001). A complete PCOS phenotype (Hirs/Oligo with BH and PCOM) was observed in 73.1% of the Hirs/Oligo group. The presence of both BH and PCOM was observed in 7.9% of the C group. The parameters with the best diagnostic performance were free androgen index ≥6.1, testosterone ≥2.4 nmol/L, follicle number ≥12 and ovarian volume ≥10 ml anti-Müllerian hormone (AMH) exhibited a low diagnostic accuracy. Hirsutism and persistent menstrual cycle over 45 days are highly associated with BH and PCOM suggesting that the presences of both criteria are necessary for the diagnosis of PCOS during adolescence.
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Hirsutismo/etiología , Oligomenorrea/etiología , Síndrome del Ovario Poliquístico/diagnóstico , Adolescente , Femenino , Humanos , Síndrome del Ovario Poliquístico/complicaciones , Adulto JovenRESUMEN
La sospecha de Síndrome de Ovario Poliquístico es un motivo de consulta frecuente durante la adolescencia, esto probablemente está dado por la sobreposición de las características fisiológicas de este período con los criterios diagnósticos tradicionalmente usados para definir este síndrome, tales como ciclos menstruales irregulares, hiperandrogenismo y morfología ecográfica de ovario poliquístico. Es por esto que parece importante discutir si los criterios diagnósticos de Síndrome de Ovario Poliquístico aplicados en mujeres adultas pueden extrapolarse a los primeros años postmenarquia. En este artículo se discute el diagnóstico de Síndrome de Ovario Poliquístico en la adolescencia, sus controversias y su manejo.
The suspicion of polycystic ovary syndrome is a common complaint during adolescence, and is probably given by the overlap of physiological characteristics of this period of life with the diagnostic criteria traditionally used to define this syndrome, such as irregular menstrual cycles, hyperandrogenism and polycystic ovarian morphology. This is why it seems important to discuss whether these diagnostic criteria for polycystic ovary syndrome in adults can be extrapolated to the early years postmenarche. This article will discuss the diagnosis of polycystic ovary syndrome in adolescence, their controversies and their management.
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Humanos , Femenino , Adolescente , Síndrome del Ovario Poliquístico/diagnóstico , Síndrome del Ovario Poliquístico/epidemiología , Síndrome del Ovario Poliquístico/clasificación , Signos y Síntomas , Chile , Causalidad , HiperandrogenismoRESUMEN
INTRODUCTION: Variations in inflammatory markers have been reported in adult women during the luteal phase, but whether these findings are observed during adolescence is unknown. We postulate that higher ultrasensitive C-reactive protein (usCRP) and lower 2-hydroxyestrone (2OHE) levels, an estrogen metabolite with cardioprotective actions, are present during the luteal phase in young women. AIM: To evaluate usCRP levels during the menstrual cycle and to determine its association with 2OHE and 16α-hydroxyestrone (16OHE) in adolescents. METHODS: Healthy postmenarcheal adolescents (N = 37) were studied during one menstrual cycle in follicular phase (FP) and luteal phase-like period (LP-L). RESULTS: Elevations in usCRP levels in the LP-L were observed in the entire group and in anovulatory cycles (1.9 ± 1.1 mg/L in FP to 2.5 ± 1.8 mg/L in LP-L; p < 0.0001). Increases in estrone, estradiol, free and bioavailable estradiol, testosterone, usCRP and 2OHE levels were observed in LP-L compared with FP (p < 0.01), with a borderline elevation in IFG-I levels (p = 0.06). CONCLUSIONS: We report an elevation of usCRP and 2OHE levels during the luteal phase in healthy adolescents. Elevations of this inflammatory marker in anovulatory adolescents without an increase in 2OHE may play a role in metabolic risks associated with chronic anovulation.
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Desarrollo del Adolescente , Proteína C-Reactiva/análisis , Fase Luteínica/sangre , Regulación hacia Arriba , Adolescente , Biomarcadores/sangre , Biomarcadores/orina , Chile , Femenino , Fase Folicular/sangre , Fase Folicular/orina , Humanos , Hidroxiestronas/orina , Fase Luteínica/orina , Progesterona/sangre , Valores de Referencia , Salud UrbanaRESUMEN
Inactivating mutations in chromodomain helicase DNA binding protein 7 (CHD7) cause CHARGE syndrome, a severe multiorgan system disorder of which Isolated gonadotropin-releasing hormone (GnRH) deficiency (IGD) is a minor feature. Recent reports have described predominantly missense CHD7 alleles in IGD patients, but it is unclear if these alleles are relevant to causality or overall genetic burden of Kallmann syndrome (KS) and normosmic form of IGD. To address this question, we sequenced CHD7 in 783 well-phenotyped IGD patients lacking full CHARGE features; we identified nonsynonymous rare sequence variants in 5.2% of the IGD cohort (73% missense and 27% splice variants). Functional analyses in zebrafish using a surrogate otolith assay of a representative set of these CHD7 alleles showed that rare sequence variants observed in controls showed no altered function. In contrast, 75% of the IGD-associated alleles were deleterious and resulted in both KS and normosmic IGD. In two families, pathogenic mutations in CHD7 coexisted with mutations in other known IGD genes. Taken together, our data suggest that rare deleterious CHD7 alleles contribute to the mutational burden of patients with both KS and normosmic forms of IGD in the absence of full CHARGE syndrome. These findings (i) implicate a unique role or preferential sensitivity for CHD7 in the ontogeny of GnRH neurons, (ii) reiterate the emerging genetic complexity of this family of IGD disorders, and (iii) demonstrate how the coordinated use of well-phenotyped cohorts, families, and functional studies can inform genetic architecture and provide insights into the developmental biology of cellular systems.
Asunto(s)
ADN Helicasas/genética , Proteínas de Unión al ADN/genética , Enfermedades Carenciales/genética , Hormona Liberadora de Gonadotropina/deficiencia , Síndrome de Kallmann/genética , Fenotipo , Pez Cebra/genética , Animales , Secuencia de Bases , Síndrome CHARGE/genética , Síndrome CHARGE/patología , ADN Helicasas/metabolismo , Proteínas de Unión al ADN/metabolismo , Técnicas de Silenciamiento del Gen , Hormona Liberadora de Gonadotropina/genética , Humanos , Datos de Secuencia Molecular , Mutación Missense/genética , Membrana Otolítica/patología , Estructura Terciaria de Proteína , Análisis de Secuencia de ADNRESUMEN
INTRODUCTION: Chlamydia trachomatis and Neisseria gonorrhoeae are responsible for 3-10% of sexually transmitted diseases in adolescents. 75% are asymptomatic. International standards recommend annual screening for C. trachomatis in sexually active women under 26 years. Self-collected vaginal swab is one of the less invasive screening methods, it is well accepted by patients and rarely used in our country. AIM: To determine the frequency of C. trachomatis and n. gonorrhoeae by a self-sampling method of vaginal swab and its acceptability in a group of adolescents and young adults. PATIENTS AND METHODS: Women 18 to 25 years old. Vaginal samples were processed by nucleic acid amplification tests, Gen Probe APTIMA Combo2. Data were collected on sexual behavior and perception of self-sampling by survey. RESULTS: We studied 344 patients with an average age of 21.7 years. Detection of C. trachomatis was positive in 7.9% women and it was not found in any of the patients studied for N. gonorrhoeae. 98% considered self-sampling instructions easy to understand, 87.5% felt comfortable taking the sample. CONCLUSIONS: Prevalence of C. trachomatis in the study population was similar to that described in other national and international studies. N. gonorrhoeae was not found in this series, which is consistent with literature reports. The self-sampling technique of vaginal sample was well accepted by the patients. However, they were anxious about the quality of the sample. According to our results, it is important to emphasize the importance of annual detection of these pathogens and that self-sampling technique is a valid alternative.
Asunto(s)
Infecciones por Chlamydia/diagnóstico , Chlamydia trachomatis/aislamiento & purificación , Gonorrea/diagnóstico , Neisseria gonorrhoeae/genética , Autocuidado/métodos , Manejo de Especímenes/métodos , Adolescente , Adulto , Chile/epidemiología , Infecciones por Chlamydia/epidemiología , Chlamydia trachomatis/genética , Estudios Transversales , Femenino , Gonorrea/epidemiología , Humanos , Neisseria gonorrhoeae/aislamiento & purificación , Prevalencia , Adulto JovenRESUMEN
Chlamydia trachomatis and Neisseria gonorrhoeae are responsible for 3-10% of sexually transmitted diseases in adolescents. 75% are asymptomatic. International standards recommend annual screening for C. trachomatis in sexually active women under 26 years. Self-collected vaginal swab is one of the less invasive screening methods, it is well accepted by patients and rarely used in our country. Aim: To determine the frequency of C. trachomatis and N. gonorrhoeae by a self-sampling method of vaginal swab and its acceptability in a group of adolescents and young adults. Patients and Methods: Women 18 to 25 years old. Vaginal samples were processed by nucleic acid amplification tests, Gen Probe APTIMA Combo2. Data were collected on sexual behavior and perception of self-sampling by survey. Results: We studied 344 patients with an average age of 21.7 years. Detection of C. trachomatis was positive in 7.9% women and it was not found in any of the patients studied for N. gonorrhoeae. 98% considered self-sampling instructions easy to understand, 87.5% felt comfortable taking the sample. Conclusions: Prevalence of C. trachomatis in the study population was similar to that described in other national and international studies. N. gonorrhoeae was not found in this series, which is consistent with literature reports. The self-sampling technique of vaginal sample was well accepted by the patients. However, they were anxious about the quality of the sample. According to our results, it is important to emphasize the importance of annual detection of these pathogens and that self-sampling technique is a valid alternative.
Chlamydia trachomatis y Neisseria gonorrhoeae son causantes de 3 a 10% de las infecciones de transmisión sexual en adolescentes. Las normas internacionales recomiendan su detección anual en mujeres sexualmente activas menores de 26 años. La adherencia a este tamizaje en mujeres jóvenes está limitada por el temor al examen ginecológico y alto costo del examen. Objetivo: Determinar la frecuencia de detección de C. trachomatis y N. gonorrhoeae por un método de auto-toma de muestra vaginal y su aceptabilidad en un grupo de adolescentes y jóvenes adultas. Pacientes y Método: Se incluyeron mujeres de 18 a 25 años atendidas en Clínica Las Condes y el Servicio de Salud Estudiantil de la Universidad de Chile, que fueron instruidas para autotoma de muestra vaginal. Luego de dar su consentimiento, las muestras fueron estudiadas mediante reacción de polimerasa en cadena para la detección de C. trachomatis y N. gonorrhoeae. Se recopilaron datos sobre conductas sexuales y percepción de la autotoma mediante encuesta. Se determinó la relación entre estos factores y la aceptabilidad del método. Resultados: Se reclutaron 344 mujeres, con una edad promedio de 21,7 años. La detección de C. trachomatis fue de 7,9% y no se encontró muestra positiva para N. gonorrhoeae. El reporte de flujo vaginal por la paciente se asoció a 1,5 veces mayor riesgo de C. trachomatis. El 98% consideró las instrucciones de la autotoma fáciles de entender, 87,5% se sintió cómoda al tomar la muestra. Conclusiones: La prevalencia de C. trachomatis en la población estudiada fue similar a lo descrito en otras series nacionales e internacionales; no se encontró N. gonorrhoeae en esta serie, lo que coincide con lo reportado en el extranjero. La técnica de autotoma de muestra vaginal fue bien aceptada por las pacientes; sin embargo, manifestaron ansiedad acerca de la seguridad de una toma adecuada. De acuerdo a nuestros resultados, es importante insistir en la detección anual de estos patógenos siendo la técnica de autotoma una alternativa válida.