F F Casanueva

Instituto de Salud Carlos III, Madrid, Madrid, Spain

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Publications (266)1026.86 Total impact

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    ABSTRACT: Obesity is a major public health threat for many industrialised countries. Bariatric surgery is the most effective treatment against obesity, suggesting that gut derived signals are crucial for energy balance regulation. Several descriptive studies have proven the presence of gastric endogenous systems that modulate energy homeostasis; however, these systems and the interactions between them are still not well known. In the present study, we show for the first time the comparative 2-DE gastric secretome analysis under different nutritional status. We have identified 38 differently secreted proteins by comparing stomach secretomes from tissue explant cultures of rats under feeding, fasting and re-feeding conditions. Among the proteins identified, glyceraldehyde-3-phosphate dehydrogenase was found to be more abundant in gastric secretome and plasma after re-feeding, and downregulated in obesity. Additionally, two calponin-1 species were decreased in feeding state, and other were modulated by nutritional and metabolic conditions. These and other secreted proteins identified in this work may be considered as potential gastrokines implicated in food intake regulation. The present work has an important impact in the field of obesity, especially in the regulation of body weight maintenance by the stomach. Nowadays, the most effective treatment in the fight against obesity is bariatric surgery, which suggests that stomach derived signals might be crucial for the regulation of the energy homeostasis. However, until now, the knowledge about the gastrokines and its mechanism of action has been poorly elucidated. In the present work, we had updated a previously validated explant secretion model for proteomic studies; this analysis allowed us, for the first time, to study the gastric secretome without interferences from other organs. We had identified 38 differently secreted proteins comparing ex vivo cultured stomachs from rats under feeding, fasting and re-feeding regimes. The results in the present article provide novel targets to study the role of the stomach in body weight and appetite regulation, and suggest new potential therapeutic targets for treating obesity. Copyright © 2015. Published by Elsevier B.V.
    Journal of proteomics. 01/2015;
  • Ana B Crujeiras, Felipe F Casanueva
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    ABSTRACT: Obesity and overweight are significantly involved in several reproductive pathologies contributing to infertility in men and women. In addition, several cancers of the reproductive system, such as endometrial, ovarian, breast, testicular and prostate cancers, are strongly influenced by obesity. However, the molecular mechanisms involved in the association between obesity and reproductive disorders remain unclear. Our proposal is to review the current scientific evidence regarding the effect of obesity-related factors as the core of the collective mechanisms directly and indirectly involved in the relationship between obesity and reproductive disorders, with a special and original focus on the effect of the obesity state microenvironment on the epigenetic profile as a reversible mechanistic link between obesity and the reproductive disorders. A PubMed search was performed using keywords related to obesity and adipose-related factors and epigenetics and associated with keywords related to reproduction. Full-text articles and abstracts in the English language published prior to 31 December 2013 were reviewed. The obesity state notably contributes to a reproductive dysfunction in both men and women, ranging from infertility to oncological outcomes. Several epidemiological and experimental studies demonstrate that factors secreted by the adipose tissue and gut in an obesity state can directly induce reproductive disturbances. Relevantly, these same factors are able to alter the epigenetic regulation of genes, a dynamic and reversible mechanism by which the organism responds to environmental pressures critical to the reproductive function. This review outlines the evidence showing that the association between the reproductive pathologies and obesity is not inevitable but is potentially preventable and reversible. The epigenetic marks related to obesity could constitute a therapeutic target for the reproductive disorders associated with obesity. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
    Human Reproduction Update 11/2014; · 8.66 Impact Factor
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    ABSTRACT: Lipodystrophies are a group of diseases mainly characterized by a loss of adipose tissue and frequently associated with insulin resistance, hypertriglyceridemia, and hepatic steatosis. In uncommon lipodystrophies, these complications frequently are difficult to control with conventional therapeutic approaches. This retrospective study addressed the effectiveness of recombinant methionyl leptin (metreleptin) for improving glucose metabolism, lipid profile, and hepatic steatosis in patients with genetic lipodystrophic syndromes. We studied nine patients (five females and four males) with genetic lipodystrophies [seven with Berardinelli-Seip syndrome, one with atypical progeroid syndrome, and one with type 2 familial partial lipodystrophy (FPLD)]. Six patients were children under age 9 years, and all patients had baseline triglycerides levels >2.26 mmol/L and hepatic steatosis; six had poorly controlled diabetes mellitus. Metreleptin was self-administered subcutaneously daily at a final dose that ranged between 0.05 and 0.24 mg/(kg day) [median: 0.08 mg/(kg day)] according to the body weight. The duration of treatment ranged from 9 months to 5 years, 9 months (median: 3 years). Plasma glucose, hemoglobin A1c (Hb A1c), lipid profile, plasma insulin and leptin, and hepatic enzymes were evaluated at baseline and at least every 6 months. Except for the patient with FPLD, metreleptin replacement significantly improved metabolic control (Hb A1c: from 10.4 to 7.1 %, p < 0.05). Plasma triglycerides were reduced 76 % on average, and hepatic enzymes decreased more than 65 %. This study extends knowledge about metreleptin replacement in genetic lipodystrophies, bearing out its effectiveness for long periods of time.
    Endocrine 11/2014; · 3.53 Impact Factor
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    ABSTRACT: Objective Meal duration may influence cardiometabolic health. The aim of this study was to explore postprandial effects of meal duration on human metabolism and appetite.DesignPostprandial comparisons following a standard meal eaten slowly over 40-minutes (‘D40’) and the same meal eaten quickly over 10-minutes (‘D10’) on a different day. Each participant therefore acted as their own control, thereby limiting confounding factors.PatientsObese pre-menopausal Caucasian women (n=10) with confirmed normoglycaemia were recruited from an Obesity clinic at UHCW, Coventry UK. Subjects underwent whole-body calorimetry (8-hours) on two separate days.MeasurementsFollowing standard lunch (D40 vs D10), 4-hour postprandial analysis included thermic effect of food (TEF) and bloods taken at pre-defined times (including baseline fasting). Analytes included lipid-profile, adiponectin, insulin, glucose, ghrelin, leptin, endotoxin, gut and pancreatic hormones. Appetite was measured using visual-analogue scales and ad libitum food intake at subsequent meal. Paired-sample t-tests (including area under the curve [AUC]) were used to compare D40 and D10 trials.ResultsPostprandial TEF (over 240-minutes) was significantly greater for D40 than D10 (mean [SEM]: 80.9Kcal [3.8] versus 29.9Kcal [3.4]; 10.6% versus 3.9% respectively, P=0.006; AUC 71.7Kcal.hr versus 22.4Kcal.hr respectively, P=0.02). Postprandial plasma NEFA was significantly lower and adiponectin levels were significantly higher for D40 than D10 (AUC [SEM]: NEFA 627μmol.hr/l [56] vs 769μmol.hr/l [60] respectively, P=0.02; adiponectin 33.4μg.hr/ml [3.9] vs 27.3μg.hr/ml [3.8] respectively, P=0.04). Other postprandial analytes and appetite measures were equivalent.Conclusions In obese women, eating slowly associates with enhanced TEF, elevated serum adiponectin and suppressed NEFA.This article is protected by copyright. All rights reserved.
    Clinical Endocrinology 11/2014; · 3.35 Impact Factor
  • Endocrinology & Metabolism Clinics of North America 11/2014; · 2.86 Impact Factor
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    ABSTRACT: The results of using HbA1C-based criteria for diagnosis of type 2 diabetes and prediabetes have been reported to differ from those obtained using fasting plasma glucose (FPG) or an oral glucose tolerance test (OGTT). We aimed to determine whether these discrepancies might be due to the influence of the glycation gap.
    Acta Diabetologica 10/2014; · 3.68 Impact Factor
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    ABSTRACT: Background: Social and lifestyle influences on age-related changes in body morphology are complex because lifestyle and physiological response to social stress can affect body fat differently. Objective: We examined the associations of socioeconomic status (SES) and lifestyle factors with body mass index (BMI) and waist circumference (WC) in middle-aged and elderly European men. Design and setting: Cross-sectional study of 3,319 men aged 40-79 recruited from eight European centres. Outcomes: We estimated relative risk ratios (RRRs) of overweight/obesity associated with unfavourable SES and lifestyles. Results: The prevalence of BMI30kg/m2 or WC102cm rose linearly with age, except in the 8th decade when high BMI, but not high WC, declined. Among men aged 40-59y, compared to non-smokers or most active men, centre and BMI adjusted RRRs for having a WC between 94-101.9cm increased by 1.6-fold in current smokers, and 2.7-fold in least active men, maximal at 2.8-fold in least active men who smoked. Similar patterns but greater RRRs were observed for men with WC≥102cm, notably 8.4-fold greater in least active men who smoked. Compared to men in employment, those who were not in employment had increased risk of having a high WC by 1.4-fold in the 40-65y group and by 1.3-fold in the 40-75y group. These relationships were weaker among elderly men. Conclusion: Unfavourable SES and lifestyles associate with increased risk of obesity, especially in middle-aged men. The combination of inactivity and smoking was the strongest predictor of high WC, providing a focus for health promotion and prevention at an early age.
    European Journal of Endocrinology 10/2014; · 3.69 Impact Factor
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    ABSTRACT: Background: Endocannabinoids and temperament traits have been linked to both physical activity and body mass index (BMI) however no study has explored how these factors interact in females. The aims of this cross-sectional study were to 1) examine differences among distinct BMI groups on daytime physical activity and time spent in moderate-vigorous physical activity (MVPA), temperament traits and plasma endocannabinoid concentrations; and 2) explore the association and interaction between MVPA, temperament, endocannabinoids and BMI.
    PLoS ONE 08/2014; 9(8):e104534. · 3.53 Impact Factor
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    ABSTRACT: Although the concept of ‘food addiction’ (FA) has raised growing interest because of evidence for similarities between substance dependence and excessive food intake, there is a lack of studies that explore this construct among the wide spectrum of eating disorders (EDs). Besides providing validation scores of a Spanish version of the Yale FA Scale (YFAS-S), this study examined the prevalence of ‘FA’ among ED subtypes compared with healthy-eating controls (HCs) and the association between ‘FA’ scores, eating symptomatology and general psychopathology. A sample of 125 adult women with ED, diagnosed according to Diagnostic and Statistical Manual of Mental Disorders 5 criteria, and 82 healthy-eating women participated in the study. All participants were assessed with the YFAS-S, the ED Inventory-2 and the Symptom Checklist-Revised. Results showed that the internal structure of the one-dimensional solution for the YFAS-S was very good (α = 0.95). The YFAS-S has a good discriminative capacity to differentiate between ED and controls (specificity = 97.6% and sensitivity (Se) = 72.8%; area under receiver operating characteristic curve = 0.90) and a good Se to screen for specific ED subtypes. YFAS-S scores were associated with higher levels of negative affect and depression, higher general psychopathology, more severe eating pathology and greater body mass index. When comparing the prevalence of ‘FA’ between ED subtypes, the lowest prevalence of ‘FA’, measured with the YFAS-S, was for the anorexia nervosa (AN) restrictive subtype with 50%, and the highest was for the AN binge–purging subtype (85.7%), followed by bulimia nervosa (81.5%) and binge eating disorder (76.9%). In conclusion, higher YFAS-S scores are associated with bingeing ED-subtype patients and with more eating severity and psychopathology. Although the ‘FA’ construct is able to differentiate between ED and HC, it needs to be further explored. Copyright © 2014 John Wiley & Sons, Ltd and Eating Disorders Association.
    European Eating Disorders Review 08/2014; · 1.38 Impact Factor
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    ABSTRACT: Background Androgens acting via the androgen receptor (AR) stimulate production of prostate specific antigen (PSA), which is a clinical marker of prostate cancer (PCa). Since genetic variants in the AR may have a significant impact on the risk of being diagnosed with PCa, the aim was to investigate if AR-variants were associated with the risk of having PSA above clinically used cut-off thresholds of 3 or 4 ng/mL in men without PCa. Methods Men without PCa history (n=1744) were selected from the European Male Ageing Study (EMAS) cohort of 40-80 year old men from 8 different European centers. Using linear and logistic regression models, with age and center as covariates, we investigated whether AR-variants (CAG repeat-length and/or SNP genotype) were associated with having serum PSA concentrations above 3 or 4 ng/mL, which often are set as cut-off concentrations for further investigation of PCa. Results Carriers of the SNP rs1204038 A-allele (16% of the men) were more likely to have PSA>3 and 4 ng/mL (OR; 95%CI 1.65; 1.13-2.40 and 1.87; 1.18-2.96, respectively) than G-allele carriers. They also had shorter CAG-repeats (median 20 vs. 23, p<0.0005), but CAG repeat length per se did not affect the PSA concentrations. Conclusion The A-allele of the SNP rs1204038 gives a 65% higher risk of having PSA above 3 ng/mL than the G-allele in men without PCa, and thereby an increased risk of being referred for further examination on suspicion of PCa. Impact Serum PSA as a clinical marker could be improved by adjustment for AR-genotype.
    07/2014;
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    ABSTRACT: Background: Both low total testosterone (T) and sex hormone binding globulin (SHBG) have been associated with an increased risk for metabolic syndrome (MetS) in men. However, serum concentrations of T are strongly linked to SHBG levels, and both are decreased in MetS. Whether the risk for MetS associated with low T is independent of SHBG, remains unclear. Furthermore, T is aromatised to estradiol (E2). The potential impact of variations in E2 on the risk for MetS has not been investigated. Objective: To study the longitudinal association of T and E2 and the risk for MetS in a large European cohort of healthy middle aged and elderly men and to assess if this risk is independent of SHBG. Methods: The European Male Ageing Study (EMAS) included 2736 community-dwelling men from 8 European countries, aged 40-79 years at baseline, followed-up for 4.3 years (range 2.95-5.7 years). MetS was defined using the ATP III criteria. Serum total T and E2 levels were measured by respectively liquid and gas chromatography/mass spectrometry. The association between baseline SHBG and sex steroids and the development of incident MetS at follow-up was assessed using logistic regression with adjustments made for age, study centre, smoking status, physical activity and general health. Results were expressed as standardised odds ratios (OR) with 95% confidence intervals (CI). Results: In the EMAS cohort, 282 men developed MetS between baseline and follow up, while 1387 men did not satisfy criteria for MetS at either time point. Men with a higher level of SHBG or total T had a significantly lower risk of developing MetS (OR 0.59 (CI 0.49-0.70, p˂0.001) and 0.58 (CI 0.50-0.68, p˂0.001), respectively). Calculated free T showed similar findings to total T. E2 was not associated with incident MetS (OR 0.99, CI 0.86-1.13, p=0.867). However, the T/E2 ratio was strongly inversely associated with incident MetS (OR 0.55, CI 0.46-0.66, p˂0.001). The inverse association between MetS and SHBG became non-significant if T was added to the model (OR 0.80, CI 0.64-1.01, p=0.064), while the association with T persisted after addition of SHBG (OR 0.67, CI 0.55-0.83). The association between E2 and incident MetS remained non-significant after adjustment for SHBG (OR 1.14, CI 0.99-1.32, p=0.074), but became significant after adjustment for T (OR 1.40, CI 1.20-1.64, p˂0.001). The T/E2 ratio remained strongly inversely associated with incident MetS even after SHBG was added to the model (OR 0.62, CI 0.51-0.75, p˂0.001). Conclusions: In men, low T, independently of SHBG and E2, predicts the development of MetS. A higher T/E2 ratio, reflecting lower aromatisation of T into E2, is linked with a reduced risk for MetS.
    ENDO 2014, Chicago; 06/2014
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    ABSTRACT: The global prevalence of obesity has significantly increased in most industrialized countries. Anti-obesity drugs are scarce, and indications to change their life style are impractical. Therefore, to identify diets able to produce significantly and maintained weight loss is mandatory. The present work evaluated the efficacy of a very low-calorie-ketogenic (VLCK) diet in obesity. A group of obese patients were randomized into two groups: the VLCK diet group and a standard low-calorie diet (LC group). The follow-up period was 12 months. Both groups received external support, counseling, to perform physical activity and adhered to the diet. The VLCK diet induced a 30-45 days of mild ketosis and significant effects on body weight within 15 days. At 2 months, the weight reductions in the VLCK diet and LC diet groups were 13.6 ± 3.9 and 4.8 ± 2.7 kg, respectively (p < 0.0001). At the end of the study, at 12 months, the weight reductions were 19.9 ± 12.3 and 7.0 ± 5.6 kg, respectively (p < 0.0001), and more than 88 % of patients in the VLCK diet group lost more of 10 % of their initial weight. Lean mass was practically unaffected. The VLCK diet was well tolerated and the side effects were moderate and transitory. In a group of obese patients, the VLCK diet was significantly more effective than a standard LC diet. At one year follow-up in the group with VLCK diet, most of the patients loss more than 10 % of their initial weight and lean mass was well preserved.
    Endocrine 03/2014; · 3.53 Impact Factor
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    ABSTRACT: FNDC5/irisin protein has been recently postulated as beneficial in the treatment of obesity and diabetes because it is induced by exercise and is able to increase energy expenditure. However, recent reports have shown that WAT also secretes irisin, and that circulating irisin is elevated in obese subjects. The aim of this study was to evaluate the circulating levels of irisin in conditions of extreme BMI, such as anorexia and obesity, and the correlations of irisin with basal metabolism and daily activity. Materials and methods: The study involved 145 female patients, including 96 patients with extreme BMIs [30 anorexic (AN) and 66 obese (OB) patients] and 49 healthy normal weight control patients (NW) to assess the circulating irisin levels. Biochemical, anthropometric and body composition measurements, daily physical activity and resting energy expenditure (REE) were analysed in the subjects. Results: The plasma irisin levels were significantly elevated in the OB patients compared with the AN and NW patients. Irisin also correlated positively with body weight, BMI and fat mass. The OB patients exhibited the highest REE and higher daily physical activity compared with the AN patients but lower activity compared with the NW patients. The irisin levels were inversely correlated with daily physical activity and directly correlated with REE. Fat mass contributed to most of the variability of the irisin plasma levels independently of the other studied parameters. Conclusions: Irisin plasma levels are influenced by energy expenditure independently of daily physical activity but fat mass is the main contributing factor
    International Journal of Endocrinology 02/2014; · 1.52 Impact Factor
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    ABSTRACT: In March 2013, the Acromegaly Consensus Group met to revise and update guidelines for the medical treatment of acromegaly. The meeting comprised experts skilled in the medical management of acromegaly. The group considered treatment goals covering biochemical, clinical and tumour volume outcomes, and the place in guidelines of somatostatin receptor ligands, growth hormone receptor antagonists and dopamine agonists, and alternative modalities for treatment including combination therapy and novel treatments. This document represents the conclusions of the workshop consensus.
    Nature Reviews Endocrinology 02/2014; · 11.03 Impact Factor
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    ABSTRACT: Objectives: Eating styles have been studied in both obesity (OB) and eating disorders (ED), but they have not been examined in these two weight conditions together. The present study explores differences in eating styles in an Anorexia Nervosa (AN) and OB sample, compared to healthy controls (HC), and it analyses their relationship with Body Mass Index (BMI) and personality traits. Method: The total sample consisted of 291 female participants (66 AN, 79 OB and 146 HC). Evaluation: Assessment measures included the Dutch Eating Behaviour Questionnaire -DEBQ- and the Temperament and Character Inventory–revised -TCI-R-. Results: The MANCOVA test showed significant differences among the three groups for all eating styles, with emotional eating being more typical in the OB group and restrained eating more typical in the AN group. Partial correlation analyses showed relationships between emotional and external eating and BMI, as well as relationships with different temperament and character traits. The stepwise discriminant function analysis showed that the DEBQ correctly classified 65.6% of the sample into the three weight categories; when combined with the TCI-R, correct classification increased to 72.6%. Conclusions: Weight conditions showed different eating behaviour patterns. Temperament and character traits were related to eating behaviours. DEBQ and TCI-R were able to discriminate between groups. Differences in eating styles in the weight groups can have implications for understanding the development and maintenance of OB and ED.
    Appetite 01/2014; 76:76-83. · 2.52 Impact Factor
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    ABSTRACT: Cushing's disease is a rare chronic disease caused by a pituitary adenoma, which leads to excess secretion of adrenocorticotropic hormone (ACTH). The over-production of ACTH leads to hyperstimulation of the adrenal glands and a chronic excess of cortisol, resulting in the signs and symptoms of a severe clinical state (Cushing's syndrome) that leads to significant morbidity, negative impacts on the patient's quality of life, and, if untreated, increased mortality. The management of patients with Cushing's disease is complicated by the heterogeneity of the condition, with signs and symptoms that overlap with those of other diseases, and high subclinical incidence rates. Controversies surrounding the tests used for screening and identifying patients with Cushing's disease add to the challenge of patient management. Surgical intervention to remove the adenoma is the first-line treatment for patients with Cushing's disease, but medical therapies are useful in patients who relapse or are unsuitable for surgery. The recent introduction of pasireotide, the first pituitary-directed medical therapy, expands the number of treatment options available for patients with Cushing's disease. This state-of-the-art review aims to provide an overview of the most recent scientific research and clinical information regarding Cushing's disease. Continuing research into improving the diagnosis and treatment of Cushing's disease will help to optimize patient management.
    Endocrine 01/2014; · 3.53 Impact Factor
  • Ana B Crujeiras, Felipe F Casanueva
    Expert Review of Endocrinology &amp Metabolism 01/2014; 7(2).
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    ABSTRACT: This study aimed to analyse the association, commonalities and differences between obesity and eating disorders (ED). A total of 150 female patients [50 obese with bulimia nervosa (OB + BN), 50 obese with binge eating disorders (OB + BED), 50 obese without eating disorders (OB)] and 50 female healthy-eating/weight control (CG) volunteers participated in this study. All participants were assessed by the Eating Disorders Inventory-2 (EDI-2), the Symptom Checklist-Revised (SCL-90-R) and the Temperament and Character Inventory-Revised. In general, all the groups differed significantly and showed linear trends (OB + BN > OB + BED > OB > CG) on general and eating psychopathology (SCL-90-R and EDI-2). Regarding personality traits, statistically significant differences across all four groups were found on Harm Avoidance and Self-Directedness. Whereas some symptoms were shared in extreme weight conditions, others were specifically related to ED. The presence of binge and purge symptomatology in obese patients is clinically relevant. These findings help to understand the relationship between Obesity and ED. Copyright © 2013 John Wiley & Sons, Ltd and Eating Disorders Association.
    European Eating Disorders Review 01/2014; 22(1):25-31. · 1.38 Impact Factor
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    ABSTRACT: We previously reported that in male patients consulting for sexual dysfunction, low prolactin (PRL) levels were associated with metabolic syndrome (MetS), arteriogenic erectile dysfunction, and incident major cardiovascular events. The aim of this study is to assess the clinical associations of PRL levels in the European Male Ageing Study (EMAS). EMAS is a prospective, observational cohort of community-dwelling men aged 40-79 years old (mean age 60 ± 11 years old). PRL was available for 2,948 men. Different parameters were evaluated including the Short Form-36 questionnaire, Becks Depression Inventory, the Adverse Life Events Scale, the Physical Activity Scale for the Elderly, and the EMAS sexual function questionnaire (EMAS-SFQ). After the adjustment for confounders, PRL levels were inversely related with worsening of sexual function as compared with the previous year, as derived from change in sexual functioning domain of the EMAS-SFQ (adj. r = -0.043; P = 0.029). The strongest correlation (Wald = 6.840; P = 0.009) was observed between lower PRL levels and reduced enjoyment of orgasmic experiences. Furthermore, an inverse relationship between PRL levels and stressful life events or depressive symptoms was observed. Low PRL was also negatively associated with an unhealthy metabolic phenotype as well as with the MetS (Wald = 5.229; P = 0.022). In line with these data, low PRL was associated with a lower level of physical activity and feeling unhealthier. Low PRL is related to several metabolic, psychological, and sexual unhealthy characteristics in European men. Checking PRL might be useful to stratify men for cardiovascular risk and to encourage appropriate lifestyle changes.
    Journal of Sexual Medicine 01/2014; 11:240. · 3.15 Impact Factor
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    ABSTRACT: Background: vitamin D deficiency has been associated with an increased risk of mortality, but whether this relationship is causal or linked to co-existent comorbidity and adverse life factors remains uncertain. Our objective was to determine whether endogenous 25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D (1,25(OH)2D) and parathyroid hormone (PTH) levels predicted all-cause, cardiovascular and cancer mortality independently of health and lifestyle factors.Setting: prospective cohort analysis within the European Male Ageing Study.Participants: 2,816 community-dwelling men aged 40-79 years at baseline.Methods: Cox regression was used to examine the association of all-cause mortality with 25(OH)D, 1,25(OH)2D and PTH; cardiovascular and cancer mortality were modelled using competing-risks regression. Results were expressed as hazard ratios (HR) and 95% confidence intervals (CIs) for Cox models; sub-hazard ratios (SHR) and 95% CIs for competing-risks models.Results: a total of 187 men died during a median of 4.3 years of follow-up. Serum levels of 25(OH)D (per 1 SD decrease: HR = 1.45; 95% CI = 1.16, 1.81) and 1,25(OH)2D (per 1 SD decrease: HR = 1.20; 95% CI = 1.00, 1.44) were associated with an increased risk of all-cause mortality after adjusting for age, centre, smoking, self-reported morbidities, physical activity and functional performance. Only levels of 25(OH)D <25 nmol/l predicted cancer mortality (SHR = 3.33; 95% CI = 1.38, 8.04).Conclusion: lower 25(OH)D and 1,25(OH)2D levels independently predicted all-cause mortality in middle-aged and older European men. Associations with cancer mortality were only observed among men with very low levels of 25(OH)D. These associations were only partially explained by the range of adverse health and lifestyle factors measured here.
    Age and Ageing 12/2013; · 3.11 Impact Factor

Publication Stats

6k Citations
1,026.86 Total Impact Points

Institutions

  • 2008–2014
    • Instituto de Salud Carlos III
      Madrid, Madrid, Spain
    • University of Patras
      • Division of Paediatrics and Obstetrics – Gynaecology
      Patrís, Kentriki Makedonia, Greece
  • 1996–2014
    • Complejo Hospitalario Universitario de Santiago
      • Department of Medicine
      Santiago, Galicia, Spain
  • 1987–2014
    • University of Santiago de Compostela
      • • Department of Medicine
      • • Departamento de Bioquímica y Biología Molecular
      • • Department of Physiology
      Santiago, Galicia, Spain
  • 2013
    • Hospital Sierrallana
      Torrelavega, Cantabria, Spain
    • Centro de Investigación Biomédica en Red-Fisiopatología de la Obesidad y la Nutrición (CIBERobn)
      Santiago, Galicia, Spain
    • University of Naples Federico II
      • Department of Clinical Medicine and Surgery
      Napoli, Campania, Italy
  • 2010–2013
    • Instituto de Investigación Sanitaria de Santiago de Compostela
      Santiago, Galicia, Spain
    • University of Pavia
      Ticinum, Lombardy, Italy
  • 2006–2013
    • Erciyes Üniversitesi
      • Department of Endocrinology
      Melikgazi, Kayseri, Turkey
  • 2012
    • University of Oxford
      Oxford, England, United Kingdom
  • 2008–2012
    • Imperial College London
      • Department of Surgery and Cancer
      London, ENG, United Kingdom
    • The University of Manchester
      Manchester, England, United Kingdom
  • 2008–2011
    • University of Leeds
      • Institute of Psychological Sciences
      Leeds, ENG, United Kingdom
  • 2009
    • University of Florence
      • Dipartimento di Scienze Biomediche, Sperimentali e Cliniche
      Florence, Tuscany, Italy
  • 2003–2008
    • Hospital Universitario Virgen del Rocío
      • Division of Endocrinology
      Hispalis, Andalusia, Spain
    • University of A Coruña
      La Corogne, Galicia, Spain
  • 2007
    • Hospital General Universitario Gregorio Marañón
      Madrid, Madrid, Spain
  • 2004–2007
    • Klinički centar Srbije
      • Institute of Endocrinology, Diabetes and Diseases of Metabolism
      Beograd, Central Serbia, Serbia
  • 1996–2005
    • University of Belgrade
      • Institute of Endocrinology
      Belgrade, SE, Serbia
  • 2001
    • University of Santiago, Chile
      CiudadSantiago, Santiago, Chile
  • 1993
    • University of Vigo
      • Faculty of Science
      Vigo, Galicia, Spain