RESUMEN
Idiopathic hypogonadotropic hypogonadism (IHH) is a rare disorder caused by the deficient production, secretion, or action of gonadotropin-releasing hormone. Prokineticin (PROK) receptor 2 ( PROKR2), a causative gene for IHH, encodes a GPCR PROKR2. When PROKR2 binds to its ligands PROKs, it may activate several signaling pathways, including IP3/Ca2+, MAPK, and cAMP pathways. However, the mutational spectrum of PROKR2 in Chinese patients with IHH has not been established. In the present study, we found that up to 13.3% (18/135) of patients with IHH in China carried mutations in PROKR2. Most of the variants in this study were private; however, a PROKR2 (c.533G > C; p.W178S) mutation was identified in 10 independent patients, implying a possible founder mutation. Functional studies indicated that 6 novel PROKR2 mutations led to decreased signaling to various extents. Two IHH-associated mutations (L218P and R270H) disrupted Gαq-dependent signaling but maintained normal Gαs and ERK1/2 signaling. A glutathione S-transferase pull-down experiment demonstrated that R270H mutation disrupted the interaction of intracellular loop 3 of PROKR2 to Gαq protein but not Gαs protein. Our results indicated that selective disruption of the interaction with a specific Gα-protein might underlie the biased signaling for certain IHH-associated PROKR2 mutations.-Zhao, Y., Wu, J., Jia, H., Wang, X., Zheng, R., Jiang, F., Chen, D.-N., Chen, Z., Li, J.-D. PROKR2 mutations in idiopathic hypogonadotropic hypogonadism: selective disruption of the binding to a Gα-protein leads to biased signaling.
Asunto(s)
Subunidades alfa de la Proteína de Unión al GTP Gq-G11/metabolismo , Hipogonadismo/genética , Mutación Missense , Mutación Puntual , Receptores Acoplados a Proteínas G/genética , Receptores de Péptidos/genética , Pueblo Asiatico/genética , AMP Cíclico/metabolismo , Femenino , Efecto Fundador , Subunidades alfa de la Proteína de Unión al GTP Gs/metabolismo , Células HEK293 , Humanos , Hipogonadismo/etnología , Sistema de Señalización de MAP Quinasas , Masculino , Mapeo de Interacción de Proteínas , Receptores Acoplados a Proteínas G/metabolismo , Receptores de Péptidos/metabolismo , Proteínas Recombinantes/metabolismo , Fracciones Subcelulares/química , Secuenciación del ExomaRESUMEN
BACKGROUND: Obesity and type 2 diabetes (T2D) are recognized as risk factors for hypogonadism in males. Serum sex hormone profiles have not been assessed adequately in obese Chinese males with T2D who have undergone Roux-en-Y gastric bypass (RYGB). OBJECTIVE: This study was conducted to examine the changes in sex hormone profiles, anthropometric parameters, and metabolic indexes before and after RYGB. SETTING: University Hospital, China. METHODS: There were 45 obese males with T2D who had undergone RYGB enrolled in this retrospective study, focusing on anthropometric parameters, metabolic indexes, and sex hormone profiles before and after surgery. RESULTS: The baseline prevalence of hypogonadism (defined by total testosterone [TT] levels<8 nM) was 33.33%. After surgery, both the levels of TT and sex hormone-binding globulin increased, while the levels of estradiol decreased. However, the calculated free testosterone, follicle-stimulating hormone, and luteinizing hormone levels remained unchanged. Multiple linear regression analysis showed that the visceral fat area was the only significant and independent parameter associated with TT levels at baseline (ß = -.479, P = .001). After surgery, decreases in the visceral fat area continued to be negatively associated with increases in TT (r = -.411, P = .024). CONCLUSION: These preliminary results demonstrated that TT could be significantly increased in obese Chinese males with T2D after RYGB; this occurs in part via a reduction in adipose tissue, especially visceral fat. Therefore, RYGB might be a promising therapy to treat hypogonadism in obese men with T2D.
Asunto(s)
Diabetes Mellitus Tipo 2/cirugía , Derivación Gástrica , Obesidad Mórbida/cirugía , Testosterona/metabolismo , Adolescente , Adulto , Glucemia/metabolismo , China/etnología , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/etnología , Hemoglobina Glucada/metabolismo , Humanos , Hipogonadismo/etnología , Hipogonadismo/cirugía , Grasa Intraabdominal/anatomía & histología , Masculino , Persona de Mediana Edad , Obesidad Mórbida/complicaciones , Obesidad Mórbida/etnología , Cuidados Posoperatorios , Cuidados Preoperatorios , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND: Androgen Deficiency in Aging Male (ADAM) questionnaire is increasingly popular for the evaluation of testosterone deficiency (TD) in Sub-Saharan African men with type 2 diabetes mellitus (T2DM). However, its reliability in this population is unknown. OBJECTIVE: To evaluate the reliability of the ADAM questionnaire for the clinical detection of testosterone deficiency in Sub-Saharan African men with T2DM. METHODS: Total testosterone < 8nmol/L was used as gold standard for diagnosis of TD in a crosssectional survey of 200 males with T2DM aged 30-69 years. Participants also completed the Saint Louis University ADAM questionnaire whereby TD was diagnosed by a "yes" answer to question 1 (reduced libido) or 7 (erectile dysfunction) or any other three questions. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and overall accuracy of the ADAM tool were computed. RESULTS: The mean age of the participants was 58.0 ± 8.8 years. 142 subjects (71.0%) had TD based on the ADAM questionnaire. However, TD was biochemically confirmed in 59 subjects (29.5%). ADAM questionnaire rendered sensitivity of 88.1%, specificity of 44.7%, PPV of 50.0%, NPV of 85.7% and accuracy of 61.4%. Low libido alone had better specificity (75.5%) and accuracy (73.2%) than the entire questionnaire. CONCLUSION: Despite an impressive sensitivity, the low specificity and overall accuracy of the ADAM questionnaire makes it unreliable for the detection of AD in Sub-Saharan African men with type 2 DM. However, presence of a sustained low libido appears to be a reliable pointer to underlying testosterone deficiency requiring biochemical confirmation.
Asunto(s)
Envejecimiento/sangre , Andrógenos/deficiencia , Diabetes Mellitus Tipo 2/complicaciones , Hipogonadismo/diagnóstico , Encuestas y Cuestionarios/normas , Testosterona/deficiencia , Adulto , África del Sur del Sahara , Anciano , Población Negra/estadística & datos numéricos , Estudios Transversales , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/etnología , Técnicas de Diagnóstico Endocrino/normas , Diseño de Investigaciones Epidemiológicas , Humanos , Hipogonadismo/sangre , Hipogonadismo/complicaciones , Hipogonadismo/etnología , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Testosterona/sangreRESUMEN
OBJECTIVE: To evaluate the relation between serum total testosterone (TT) and prostate cancer (PCa) grade and the effect of race and demographic characteristics on such association. METHOD: We analyzed 695 patients undergoing radical prostatectomy (RP), of whom 423 had serum TT collected. Patients were classified as having hypogonadism or eugonadism based on two thresholds of testosterone: threshold 1 (300 ng/dL) and threshold 2 (250 ng/dL). We evaluated the relation between TT levels and a Gleason score (GS) ≥ 7 in RP specimens. Outcomes were evaluated using univariate and multivariate analyses, accounting for race and other demographic predictors. RESULTS: Out of 423 patients, 37.8% had hypogonadism based on the threshold 1 and 23.9% based on the threshold 2. Patients with hypogonadism, in both thresholds, had a higher chance of GS ≥ 7 (OR 1.79, p=0.02 and OR 2.08, p=0.012, respectively). In the multivariate analysis, adjusted for age, TT, body mass index (BMI) and race, low TT (p=0.023) and age (p=0.002) were found to be independent risk factors for GS ≥ 7. Among Black individuals, low serum TT was a stronger predictor of high-grade disease compared to White men (p=0.02). CONCLUSION: Hypogonadism is independently associated to higher GS in localized PCa. The effect of this association is significantly more pronounced among Black men and could partly explain aggressive characteristics of PCa found in this race.
Asunto(s)
Hipogonadismo/sangre , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/sangre , Testosterona/sangre , Testosterona/deficiencia , Humanos , Hipogonadismo/complicaciones , Hipogonadismo/etnología , Masculino , Clasificación del Tumor , Pronóstico , Neoplasias de la Próstata/complicaciones , Neoplasias de la Próstata/etnología , Neoplasias de la Próstata/patología , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Summary Objective: To evaluate the relation between serum total testosterone (TT) and prostate cancer (PCa) grade and the effect of race and demographic characteristics on such association. Method: We analyzed 695 patients undergoing radical prostatectomy (RP), of whom 423 had serum TT collected. Patients were classified as having hypogonadism or eugonadism based on two thresholds of testosterone: threshold 1 (300 ng/dL) and threshold 2 (250 ng/dL). We evaluated the relation between TT levels and a Gleason score (GS) ≥ 7 in RP specimens. Outcomes were evaluated using univariate and multivariate analyses, accounting for race and other demographic predictors. Results: Out of 423 patients, 37.8% had hypogonadism based on the threshold 1 and 23.9% based on the threshold 2. Patients with hypogonadism, in both thresholds, had a higher chance of GS ≥ 7 (OR 1.79, p=0.02 and OR 2.08, p=0.012, respectively). In the multivariate analysis, adjusted for age, TT, body mass index (BMI) and race, low TT (p=0.023) and age (p=0.002) were found to be independent risk factors for GS ≥ 7. Among Black individuals, low serum TT was a stronger predictor of high-grade disease compared to White men (p=0.02). Conclusion: Hypogonadism is independently associated to higher GS in localized PCa. The effect of this association is significantly more pronounced among Black men and could partly explain aggressive characteristics of PCa found in this race.
Resumo Objetivo: Avaliar a relação entre testosterona sérica total (TT) e grau do câncer de próstata (CP) e o efeito da raça e de características demográficas sobre essa associação. Método: Foram analisados 695 pacientes submetidos a prostatectomia radical (PR), dos quais 423 tinham medidas dos níveis séricos de TT. Os pacientes foram classificados como portadores de hipogonadismo ou eugonadismo com base em dois limites de testosterona: limite 1 (300 ng/dL) e limite 2 (250 ng/dL). Avaliou-se a relação entre nível de TT e escore Gleason (GS) ≥ 7 em amostras de PR. Os resultados foram avaliados por análises univariada e multivariada, com ajuste para raça e outros fatores prognósticos demográficos. Resultados: Do total de 423 pacientes, 37,8% apresentavam hipogonadismo com base no limite 1, e 23,9% com base no limite 2. Os pacientes com hipogonadismo, independentemente do limite de referência, tiveram uma chance maior de GS ≥ 7 (OR 1,79, p=0,02 e OR 2,08, p=0,012, respectivamente). Na análise multivariada, após ajuste para idade, TT, índice de massa corporal (IMC) e raça, baixo TT (p=0,023) e idade (p=0,002) foram considerados fatores de risco independentes para GS ≥ 7. Entre os indivíduos negros, baixo TT sérico foi mais preditivo de doença de alto grau em comparação com os brancos (p=0,02). Conclusão: O hipogonadismo é independentemente associado a escores mais altos de GS no CP localizado. O efeito dessa associação é significativamente mais pronunciado entre homens negros, o que poderia explicar, em parte, as características agressivas do CP observadas nessa população.
Asunto(s)
Humanos , Masculino , Neoplasias de la Próstata/sangre , Testosterona/deficiencia , Testosterona/sangre , Antígeno Prostático Específico/sangre , Hipogonadismo/sangre , Pronóstico , Neoplasias de la Próstata/complicaciones , Neoplasias de la Próstata/etnología , Neoplasias de la Próstata/patología , Estudios Retrospectivos , Factores de Riesgo , Clasificación del Tumor , Hipogonadismo/complicaciones , Hipogonadismo/etnologíaRESUMEN
OBJECTIVE: To retrospectively validate the American Society for Reproductive Medicine (ASRM) guidelines/recommendations concerning endocrine evaluation in a cohort of white European men presenting for couple's infertility. DESIGN: Retrospective study. SETTING: Academic reproductive medicine outpatient clinic. PATIENT(S): Cohort of 1,056 consecutive infertile men (noninterracial infertile couples). INTERVENTION(S): Testicular volume was assessed with a Prader orchidometer. Serum hormones were measured (8-10 a.m.) in all cases. Hypogonadism was defined as total T < 3 ng/mL, according to the Endocrine Society definition. Semen analysis values were assessed based on the 2010 World Health Organisation reference criteria. MAIN OUTCOME MEASURE(S): ASRM indications for endocrine assessment in infertile men (sperm concentration <10 million/mL, impaired sexual function, and other clinical ï¬ndings suggesting a speciï¬c endocrinopathy) were used to predict hypogonadism in our cohort. Moreover, a clinically user-friendly three-item nomogram was developed to predict hypogonadism and was compared to the ASRM guidelines assessment. RESULT(S): Biochemical hypogonadism was diagnosed in 156 (14.8%) men. Overall, 669 (63.4%) patients would have necessitated total T assessment according to the ASRM criteria; of these, only 119 (17.8%) were actually hypogonadal according to the Endocrine Society classification criteria. Conversely, 37 (23.7%) out of 156 patients with biochemical hypogonadism would have been overlooked. The overall predictive accuracy, sensitivity, and specificity of the ASRM guidelines was 58%, 76%, and 39%, respectively. Our nomogram was not reliable enough to predict hypogonadism, despite demonstrating a significantly higher predictive accuracy (68%) than the ASRM guidelines. CONCLUSION(S): The current findings show that the ASRM guidelines/recommendations for male infertility workup may not be suitable for application in white European infertile men.
Asunto(s)
Técnicas de Apoyo para la Decisión , Técnicas de Diagnóstico Endocrino/normas , Fertilidad , Hipogonadismo/diagnóstico , Infertilidad Masculina/diagnóstico , Nomogramas , Guías de Práctica Clínica como Asunto/normas , Población Blanca , Adulto , Biomarcadores/sangre , Estudios Transversales , Adhesión a Directriz/normas , Humanos , Hipogonadismo/sangre , Hipogonadismo/etnología , Hipogonadismo/fisiopatología , Infertilidad Masculina/sangre , Infertilidad Masculina/etnología , Infertilidad Masculina/fisiopatología , Italia/epidemiología , Masculino , Tamaño de los Órganos , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Recuento de Espermatozoides , Testículo/patología , Testosterona/sangreRESUMEN
Kallmann syndrome, a form of idiopathic hypogonadotropic hypogonadism, is characterized by developmental abnormalities of the reproductive system and abnormal olfaction. Despite association of certain genes with idiopathic hypogonadotropic hypogonadism, the genetic inheritance and expression are complex and incompletely known. In the present study, seven Kallmann syndrome pedigrees in an ethnic Han Chinese population were screened for genetic mutations. The exons and intron-exon boundaries of 19 idiopathic hypogonadotropic hypogonadism (idiopathic hypogonadotropic hypogonadism)-related genes in seven Chinese Kallmann syndrome pedigrees were sequenced. Detected mutations were also tested in 70 sporadic Kallmann syndrome cases and 200 Chinese healthy controls. In pedigrees 1, 2, and 7, the secondary sex characteristics were poorly developed and the patients' sense of smell was severely or completely lost. We detected a genetic mutation in five of the seven pedigrees: homozygous KAL1 p.R191ter (pedigree 1); homozygous KAL1 p.C13ter (pedigree 2; a novel mutation); heterozygous FGFR1 p.R250W (pedigree 3); and homozygous PROKR2 p.Y113H (pedigrees 4 and 5). No genetic change of the assayed genes was detected in pedigrees 6 and 7. Among the 70 sporadic cases, we detected one homozygous and one heterozygous PROKR2 p.Y113H mutation. This mutation was also detected heterozygously in 2/200 normal controls and its pathogenicity is likely questionable. The genetics and genotype-phenotype relationships in Kallmann syndrome are complicated. Classical monogenic inheritance does not explain the full range of genetic inheritance of Kallmann syndrome patients. Because of stochastic nature of genetic mutations, exome analyses of Kallmann syndrome patients may provide novel insights.
Asunto(s)
Análisis Mutacional de ADN , Síndrome de Kallmann/etnología , Síndrome de Kallmann/genética , Adolescente , Adulto , Secuencia de Aminoácidos , Niño , China , Codón sin Sentido , Exones , Proteínas de la Matriz Extracelular/genética , Salud de la Familia , Femenino , Estudios de Asociación Genética , Heterocigoto , Homocigoto , Humanos , Hipogonadismo/etnología , Hipogonadismo/genética , Intrones , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Proteínas del Tejido Nervioso/genética , Linaje , Fenotipo , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/genética , Receptores Acoplados a Proteínas G/genética , Receptores de Péptidos/genética , Homología de Secuencia de Aminoácido , Adulto JovenRESUMEN
BACKGROUND: Human mutations in the gonadotropin-releasing hormone receptor (GnRHR) gene cause normosmic idiopathic hypogonadotropic hypogonadism (IHH). At least 19 different mutations have been identified in this G-protein-coupled receptor, which consist mostly of missense mutations. OBJECTIVES: To identify and determine the frequency of mutations in the coding region of the gonadotropin-releasing hormone receptor (GnRHR) gene in forty Chinese patients with normosmic idiopathic hypogonadotropic hypogonadism (IHH) and establish genotype/phenotype correlations where possible. METHODS: The diagnosis of HH was based on absent or incomplete sexual development after 17 years of age in girls and 18 years in boys associated with low or normal levels of LH in both sexes and low levels of testosterone in males and of estradiol in females. All patients presented with a normal sense of smell in an olfactory specific test. Forty IHH patients and 40 controls were screened for mutations in the coding sequence of the GnRHR gene. The coding region of the GnRHR gene was amplified by PCR and directly sequenced. RESULTS: A missense mutation, serine 168 arginine (S168R), located in the fourth transmembrane domain of the GnRHR gene, was identified as being in a homozygous state in one male with complete HH. The S168R mutation has been previously shown to be a cause in the complete loss of receptor function because hormone binding to the receptor is completely impaired. In another patient, a compound heterozygous mutation (Gln106Arg and Arg262Gln) was identified in a male with partial HH. The Gln106Arg mutation is located in the first extracellular loop of GnRH-R, this mutation decreases but not does eliminate GnRH binding; while Arg262Gln mutation is located in the third extracellular loop of GnRH-R and only decreases signal transduction. A good correlation between genotype and phenotype was found in our patients. The patient, who was homozygous for the completely inactivating S168R mutation, had complete HH. In addition, the affected patient who was compound heterozygous for the Glnl06Arg--Arg262Gln mutations - has partial HH. CONCLUSIONS: GnRHR mutations can be classified into partial or complete loss of function mutations. Partially inactivating substitutions of the GnRHR frequently found in familial hypogonadotrophic hypogonadism are Q106R and R262Q. Comparison of compound heterozygous with homozygous patients suggests that their phenotype and the response to GnRH is determined by the GnRHR variant with the less severe loss of function.
Asunto(s)
Hipogonadismo/genética , Receptores LHRH/genética , Adolescente , Secuencia de Aminoácidos , Pueblo Asiatico/genética , Secuencia de Bases , Análisis Mutacional de ADN , Femenino , Predisposición Genética a la Enfermedad , Humanos , Hipogonadismo/clasificación , Hipogonadismo/diagnóstico , Hipogonadismo/etnología , Masculino , Modelos Biológicos , Datos de Secuencia Molecular , Mutación Missense , Pubertad Tardía/diagnóstico , Pubertad Tardía/genética , Índice de Severidad de la EnfermedadRESUMEN
PURPOSE: To observe hypogonadal men undergoing testosterone replacement therapy (TRT) and assess racial differences in hypogonadal improvement and prostate-specific antigen (PSA) levels. MATERIALS AND METHODS: In a retrospective analysis, 75 hypogonadal men were followed for an average 34 months after initiating TRT. Total testosterone and PSA levels were assessed every 6 months, and patients diagnosed with prostatitis or prostate cancer during treatment were excluded. RESULTS: For 16 African American men, the average age at diagnosis of hypogonadism was 53.5 years, compared with 57.8 years in 59 Caucasian men (p=NS). Pre- and post-treatment testosterone was 219 ng/dL and 310 ng/dL in African American men, and 247 ng/dL and 497 ng/dL in Caucasian men (p=NS). Symptomatic response was 81% in African American men and 93% in Caucasian men (p=NS). Baseline PSA level was 1.32 ng/mL in African American men and 1.27 ng/mL in Caucasian men, and there was no significant difference in PSA between racial groups at 6-month intervals, although there was a small decreasing trend in the PSA of African Americans compared with Caucasians. CONCLUSIONS: Hypogonadal African American men have a similar normalization of testosterone and symptomatic response as hypogonadal Caucasian men, and PSA levels remain stable over time in both groups. In this hypogonadal cohort, in contrast to studies of eugonadal men, higher PSA levels in African Americans were not observed.
Asunto(s)
Terapia de Reemplazo de Hormonas , Hipogonadismo/terapia , Antígeno Prostático Específico/análisis , Testosterona/deficiencia , Testosterona/uso terapéutico , Adulto , Negro o Afroamericano , Anciano , Anciano de 80 o más Años , Estudios de Seguimiento , Humanos , Hipogonadismo/etnología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento , Población Blanca , Adulto JovenRESUMEN
PURPOSE: To observe hypogonadal men undergoing testosterone replacement therapy (TRT) and assess racial differences in hypogonadal improvement and prostate-specific antigen (PSA) levels. MATERIALS AND METHODS: In a retrospective analysis, 75 hypogonadal men were followed for an average 34 months after initiating TRT. Total testosterone and PSA levels were assessed every 6 months, and patients diagnosed with prostatitis or prostate cancer during treatment were excluded. RESULTS: For 16 African American men, the average age at diagnosis of hypogonadism was 53.5 years, compared with 57.8 years in 59 Caucasian men (p = NS). Pre- and post-treatment testosterone was 219 ng/dL and 310 ng/dL in African American men, and 247 ng/dL and 497 ng/dL in Caucasian men (p = NS). Symptomatic response was 81 percent in African American men and 93 percent in Caucasian men (p = NS). Baseline PSA level was 1.32 ng/mL in African American men and 1.27 ng/mL in Caucasian men, and there was no significant difference in PSA between racial groups at 6-month intervals, although there was a small decreasing trend in the PSA of African Americans compared with Caucasians. CONCLUSIONS: Hypogonadal African American men have a similar normalization of testosterone and symptomatic response as hypogonadal Caucasian men, and PSA levels remain stable over time in both groups. In this hypogonadal cohort, in contrast to studies of eugonadal men, higher PSA levels in African Americans were not observed.
Asunto(s)
Adulto , Anciano , Anciano de 80 o más Años , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Terapia de Reemplazo de Hormonas , Hipogonadismo/terapia , Antígeno Prostático Específico/análisis , Testosterona/deficiencia , Testosterona/uso terapéutico , Negro o Afroamericano , Población Blanca , Estudios de Seguimiento , Hipogonadismo/etnología , Estudios Retrospectivos , Factores de Tiempo , Resultado del TratamientoRESUMEN
CONTEXT: Osteoporosis primarily affects postmenopausal women. However, young women with estrogen deficiency also are at increased risk for low bone density. OBJECTIVE: The aim of the study was to assess bone density and associated risk factors for reduced bone density in young, estrogen-deficient women using primary ovarian insufficiency (POI) as the disease model. DESIGN AND SETTING: We conducted a cross-sectional study at a tertiary care research center. PARTICIPANTS: We studied women with POI (n = 442), concurrent controls (n = 70), and matched controls from NHANES III (n = 353). PRIMARY OUTCOME MEASURE: We measured bone mineral density (BMD) using dual-energy x-ray absorptiometry. RESULTS: Patients on average had 2-3% lower BMD at L1-L4, femoral neck, and total hip (P < 0.01 at all sites). The modifiable risk factors for BMD below the expected range for age (Z-score <-2) were: more than 1-yr delay in diagnosis of estrogen deficiency (P = 0.018), low (<32 ng/ml) vitamin D levels (P = 0.002), estrogen replacement nonadherence (P = 0.002), low calcium intake (P = 0.005), and lack of exercise (P = 0.005). As compared to Caucasians, African-American and Asian women with POI were 3.18 and 4.34 times more likely, respectively, to have Z-scores below -2 (P = < 0.0001 for both). Race was an overall risk factor, but on regression modeling, not an independent predictor of low bone density. CONCLUSIONS: Women with POI have lower bone density compared to regularly menstruating women. Compared to Caucasians, minority women with estrogen deficiency are more likely to have BMD below the expected range for age. This racial disparity appears to be related to a combined effect of several modifiable risk factors. Delay in diagnosis of POI also contributes to reduced bone density by delaying proper therapy.
Asunto(s)
Densidad Ósea , Estrógenos/deficiencia , Hipogonadismo/fisiopatología , Adulto , Densidad Ósea/fisiología , Estudios de Casos y Controles , Estudios Transversales , Femenino , Cuello Femoral/diagnóstico por imagen , Cadera/diagnóstico por imagen , Humanos , Hipogonadismo/complicaciones , Hipogonadismo/diagnóstico por imagen , Hipogonadismo/etnología , Región Lumbosacra/diagnóstico por imagen , Osteoporosis/diagnóstico por imagen , Osteoporosis/epidemiología , Osteoporosis/etnología , Osteoporosis/etiología , Enfermedades del Ovario/complicaciones , Enfermedades del Ovario/etiología , Enfermedades del Ovario/fisiopatología , Radiografía , Factores de Riesgo , Adulto JovenRESUMEN
BACKGROUND: A 10-question screening questionnaire for androgen deficiency in aging men (ADAM) was reported in previous white but not Chinese populations. We therefore investigated the validity of a Chinese version of the Saint Louis University ADAM questionnaire to screen for androgen deficiency in Chinese men. METHODS: This was a cross-sectional study. Seven hundred ninety-six ambulatory community-based Chinese men, 18-89 years old, were recruited from October 2003 through June 2006. Self-administered Chinese ADAM questionnaire and morning blood samples for serum total testosterone (TT) and bioavailable testosterone (BT) levels were collected from all participants. Low serum BT levels (androgen deficiency) were defined as <5th percentile of serum BT levels in young healthy Chinese men (18-29 years). RESULTS: The Chinese ADAM questionnaire had good internal consistency (Cronbach alpha = 0.74) and test-retest reliability (Pearson correlation coefficient, r = 0.86; p <.001, two-tailed). As a screening test for low serum BT levels, the Chinese ADAM questionnaire has a high sensitivity of 88% but low specificity of 32%. In 6 of the 10 questions, the mean serum BT levels were significantly lower in those who answered positively than in those who answered negatively. Using a cut-off score of > or =2, a six-question short Chinese ADAM questionnaire demonstrated sensitivity, specificity, and positive and negative predictive values of 86%, 40%, 46%, and 82%, respectively. CONCLUSION: We have validated a full Chinese version and developed a shortened version of the ADAM questionnaire, and demonstrated that they are sensitive but not specific screening tests for androgen deficiency in Chinese men.
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Andrógenos/deficiencia , Andropausia , Pueblo Asiatico/estadística & datos numéricos , Hipogonadismo/diagnóstico , Hipogonadismo/etnología , Encuestas y Cuestionarios , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Andrógenos/sangre , Comparación Transcultural , Estudios Transversales , Humanos , Masculino , Tamizaje Masivo , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Testosterona/sangre , Población Blanca/estadística & datos numéricosRESUMEN
OBJECTIVE: To date, Micro syndrome has been reported in only three children from one family. We describe an additional 14 children from 11 families. DESIGN: Retrospective case series. PARTICIPANTS: Fourteen children from 11 families attending one of five British hospitals. MAIN OUTCOME MEASURES: The following features were documented: pre- and postoperative eye findings, electrophysiologic analysis, systemic abnormalities, development, neuroimaging, genealogy, geographic origin of family. RESULTS: We expand and modify the description of ocular and electrophysiologic findings in Micro syndrome. The eye findings of microphakia, microphthalmos, characteristic lens opacity, and atonic pupils were the presenting feature in all infants and were the most reliable diagnostic signs in the immediate postnatal period. Cortical visual impairment, microcephaly, and developmental delay were not always detectable initially; they developed in all children by 6 months of age. Microgenitalia were a useful diagnostic clue in affected males only. Therefore, eye features were more consistently useful in determining diagnosis than dysmorphology or brain imaging. The families of all the children originate from the Muslim population of Northern Pakistan. Inheritance is likely to be autosomal recessive. CONCLUSIONS: Micro syndrome usually presents to the ophthalmologist, who may be able to make the diagnosis on the basis of characteristic eye findings combined with ethnic origin. Initially, the nature and severity of nonophthalmic features are not apparent. Early diagnosis of the underlying condition is important to guide management of the cataracts, glaucoma, and developmental delay. It is helpful for the family and medical staff to be aware of the low level of vision that develops despite optimal ophthalmic intervention. Genetic counseling extending into the wider family is particularly important in view of the high rate of consanguinity.