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Pye S.R.,University of Manchester | Huhtaniemi I.T.,Imperial College London | Finn J.D.,University of Manchester | Lee D.M.,University of Manchester | And 17 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2014

Context: Late-onset hypogonadism (LOH) has recently been defined as a syndrome in middle-aged and elderly men reporting sexual symptoms in the presence of low T. The natural history of LOH, especially its relationship to mortality, is currently unknown. Objective: The aim of this study was to clarify the associations between LOH, low T, and sexual symptoms with mortality in men. Design, Setting, and Participants: Prospective data from the European Male Aging Study (EMAS) on 2599 community-dwelling men aged 40 -79 years in eight European countries was used for this study. Main Outcome Measure(s): All-cause, cardiovascular, and cancer-related mortality was measured. Results: One hundred forty-seven men died during a median follow-up of 4.3 years. Fifty-five men (2.1%) were identified as having LOH (31 moderate and 24 severe). After adjusting for age, center, body mass index (BMI), current smoking, and poor general health, compared with men without LOH, those with severe LOH had a 5-fold [hazard ratio (HR) 5.5; 95% confidence interval (CI) 2.7, 11.4] higher risk of all-cause mortality. Compared with eugonadal men, the multivariable-adjusted risk of mortality was 2-fold higher in those with T less than 8 nmol/L (irrespective of symptoms; HR 2.3; 95% CI 1.2, 4.2) and 3-fold higher in those with three sexual symptoms (irrespective of serum T; compared with asymptomatic men; HR 3.2; 95% CI 1.8, 5.8). Similar risks were observed for cardiovascular mortality. Conclusions: Severe LOH is associated with substantially higher risks of all-cause and cardiovascular mortality, to which both the level of T and the presence of sexual symptoms contribute independently. Detecting low T in men presenting with sexual symptoms offers an opportunity to identify a small subgroup of aging men at particularly high risk of dying. Copyright © 2014 by the Endocrine Society. Source


Vanderschueren D.,Catholic University of Leuven | Pye S.R.,University of Manchester | O'Neill T.W.,University of Manchester | Lee D.M.,University of Manchester | And 22 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2013

Context: There is little information on the potential impact of serum 1,25-dihydroxyvitamin D [1,25(OH)2D] on bone health including turnover. Objective: The objective of the study was to determine the influence of 1,25(OH)2D and 25-hydroxyvitamin D [25(OH)D] on bone health in middle-aged and older European men. Design, Setting, and Participants: Men aged 40-79 years were recruited from population registers in 8 European centers. Subjects completed questionnaires that included questions concerning lifestyle and were invited to attend for quantitative ultrasound (QUS) of the heel, assessment of height and weight, and a fasting blood sample from which 1,25(OH)2D, 25(OH)D, and PTH were measured. 1,25(OH)2D was measured using liquid chromatography tandem mass spectrometry. Bone markers serum N-terminal propeptide of type 1 procollagen (P1NP) and crosslinks (β-cTX) were also measured. Dual-energy x-ray absorptiometry (DXA) of the hip and lumbar spine was performed in 2 centers. Main Outcome Measure(s):QUSof the heel, bone markers P1NP and β-cTX, and DXA of the hip and lumbar spine were measured. Results: A total of 2783 men, mean age 60.0 years (SD 11.0) were included in the analysis. After adjustment for age and center, 1,25(OH) 2D was positively associated with 25(OH)D but not with PTH. 25(OH)D was negatively associated with PTH. After adjustment for age, center, height, weight, lifestyle factors, and season, 1,25(OH)2D was associated negatively with QUS and DXA parameters and associated positively with β-cTX. 1,25(OH)2D was not correlated with P1NP. 25(OH)D was positively associated with the QUS and DXA parameters but not related to eitherbone turnover marker. Subjects with both high 1,25(OH)2D (upper tertile) and low 25(OH)D (lower tertile) had the lowest QUS and DXA parameters and the highest β-cTX levels. Conclusions: Serum 1,25(OH)2D is associated with higher bone turnover and poorer bone health despite being positively related to 25(OH)D. A combination of high 1,25(OH)2D and low 25(OH)D is associated with the poorest bone health. Copyright © 2013 by The Endocrine Society. Source


Bernabeu I.,University of Santiago de Compostela | Alvarez-Escola C.,Hospital Universitario La Paz | Lucas T.,Autonomous University of Madrid | Puig-Domingo M.,University of Barcelona | And 7 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2010

Context: The deletion of exon 3 in the GH receptor (GHR) has been associated with a different biochemical picture and response to therapy in acromegaly. Objective: The aim of the study was to determine whether or not the GHR genotype influences the efficacy of pegvisomant treatment. Design and Setting: A cross-sectional study was conducted in six Spanish university hospitals. Patients: Forty-four acromegalic patients with active disease and resistance to somatostatin analogs participated in the study. Results: The prevalence of the full-length GHR and the exon 3-deleted GHR homozygous and heterozygous genotypes was 41, 2, and 57%, respectively. There were no differences in IGF-I or GH prepegvisomant levels related to GHR genotype. The exon 3-deleted patients required approximately 20% lower doses of pegvisomant per kilogram of weight (28±11 compared to 22±7mgper kg of weight; P = 0.033) to normalize IGF-I. A stepwise multivariate linear regression analysis (R2 = 0.27; P = 0.003) identified male gender (β = -0.79; P = 0.03) and d3-GHR genotype (β = -0.64; P = 0.007) as the only significant predictors of the dose of pegvisomant per kilogram of weight. In addition, d3-GHR carriers required fewer months for IGF-I normalization (P < 0.01). A stepwise multivariate linear regression analysis (R2 = 0.40; P = 0.001) revealed that the only significant predictor of the time to IGF-I normalization was the dose of pegvisomant per kilogram of weight (β = 0.451; P = 0.001). Conclusions: The exon 3 deletion in the GHR predicts an improved response to pegvisomant therapy in acromegaly. Copyright © 2010 by The Endocrine Society. Source


Fernandez-Rodriguez E.,University of Santiago de Compostela | Bernabeu I.,University of Santiago de Compostela | Castro A.I.,University of Santiago de Compostela | Kelestimur F.,Erciyes University | And 2 more authors.
Frontiers in Endocrinology | Year: 2010

Neuroendocrine dysfunction, long recognized as a consequence of traumatic brain injury (TBI), is a major cause of disability that includes physical and psychological involvement with long-term cognitive, behavioral, and social changes. There is no standard procedure regarding at what time after trauma the diagnosis should be made. Also there is uncertainty on defining the best methods for diagnosis and testing and what types of patients should be selected for screening. Common criteria for evaluating these patients are required on account of the high prevalence of TBI worldwide and the potential new cases of hypopituitarism. The aim of this review is to clarify, based on the evidence, when endocrine assessment should be performed afterTBI and which patients should be evaluated. Additional studies are still needed to know the impact of post-traumatic hypopituitarism and to assess the impact of hormone replacement in the prognosis. © 2011 Fernandez-Rodriguez, Bernabeu,Castro,Kelestimurand Casanueva. Source


Gamundi-Segura S.,University Institute of Health Sciences | Torres-Perez E.,University Institute of Health Sciences | Sanz-Paris A.,Servicio Of Endocrinologia tricion Hospital Universitario Miguel Servet | Arbones-Mainar J.M.,University Institute of Health Sciences | Arbones-Mainar J.M.,Instituto Salud Carlos III
Fertility and Sterility | Year: 2016

Objective To evaluate whether [1] apolipoprotein E (APOE) polymorphisms can differentially regulate miscarriage risk and [2] whether this genotype effect could also be modulated by the race within populations. Design Data were derived from the Coronary Artery Risk Development in Young Adults (CARDIA), a longitudinal study with black and white participants from four U.S. locations. Setting Not applicable. Patient(s) Women without miscarriages (controls) and women who miscarried at least once (cases). Intervention(s) None. Main Outcome Measure(s) A group of women (n = 1,372) successfully followed for 25 years and with their APOE alleles identified were analyzed for miscarriage risk throughout their reproductive life. Additionally, a larger longitudinal analysis encompassing all the participants who had their APOE characterized (n = 2,140) was also performed for the association between APOE and miscarriage risk. Result(s) In white women followed up for 25 years, the odds ratio for miscarriage associated with APOE*2 allele presence was 1.61 (95% confidence interval, 1.04–2.50) compared with APOE*33 carriers. This was a race-dependent phenomenon as no associations between APOE alleles and miscarriage was observed in black women. Likewise, Cox regression analysis showed that cumulative miscarriage risk in white women was 37.2% in the APOE*2 carriers compared with 27.8% and 24.8% in APOE*33 and APOE*4 carriers, respectively. With APOE*33 as the reference, the age-adjusted hazard ratio associated with carrying the APOE*2 allele was 1.47 (95 confidence interval, 1.06–2.05). Conclusion(s) This variable miscarriage risk, produced by an interaction between genotype and race, may reconcile, at least partially, the conflicting reports of the association of APOE and miscarriage risk. © 2016 American Society for Reproductive Medicine Source

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