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  • Author: Allan Linneberg x
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Morten Ruge Center for Clinical Research and Disease Prevention, Bispebjerg and Frederiksberg Hospital, The Capital Region, Copenhagen, Denmark

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Tea Skaaby Center for Clinical Research and Disease Prevention, Bispebjerg and Frederiksberg Hospital, The Capital Region, Copenhagen, Denmark

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Anna-Maria Andersson Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

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Allan Linneberg Center for Clinical Research and Disease Prevention, Bispebjerg and Frederiksberg Hospital, The Capital Region, Copenhagen, Denmark
Department of Clinical Experimental Research, Rigshospitalet, Copenhagen, Denmark
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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Background

Reduced total hours of sleep and low quality of sleep have been suggested to be associated with low levels of male hormones. Few studies have examined the association between excessive sleep and male reproductive hormones.

Objective

To investigate the association of total hours of sleep and quality of sleep with serum levels of total, bioavailable and free testosterone (tT, bT and fT), sex hormone-binding globulin (SHBG) and dehydroepiandrosteron-sulfate (DHEAS).

Methods

Serum levels of tT, SHBG and DHEAS were measured with immunoassays in a cross-sectional population-based study of 2095 males. bT and fT were calculated in accordance with Vermeulens method. Information on total hours of sleep and sleep quality was obtained by questionnaire. Linear regression was used to calculate hormones according to total hours of sleep and the results were expressed as β-estimates and 95% confidence intervals (CI). The adjustment in the multivariable models was constructed taking age, BMI, smoking, alcohol intake and physical activity into account.

Results

Excessive sleep (>9 h) compared to 7–9 h of sleep was significantly associated with lower tT, bT and fT, but not with SHBG or DHEAS, after multivariable adjustment. These significant associations were also found in our analyses with hormones as continuous variables but no associations were found in our general additive model analyses.

Conclusions

In this cross-sectional study in men, excessive sleep associated with lower levels of male reproductive hormones. Longitudinal studies are needed to determine the causal direction of the observed association between excessive sleep and lower male reproductive hormones levels.

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Stine A Holmboe Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Blegdamsvej, Copenhagen, Denmark
The International Research Centre in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

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Ravi Jasuja Research Program in Men’s Health: Aging and Metabolism, Brigham and Womens Hospital, Harvard Medical School, Boston, Massachusetts, USA

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Brian Lawney Research Program in Men’s Health: Aging and Metabolism, Brigham and Womens Hospital, Harvard Medical School, Boston, Massachusetts, USA

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Lærke Priskorn Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Blegdamsvej, Copenhagen, Denmark
The International Research Centre in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

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Niels Joergensen Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Blegdamsvej, Copenhagen, Denmark
The International Research Centre in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

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Allan Linneberg Centre for Clinical Research and Prevention, Frederiksberg Hospital, Copenhagen, Denmark
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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Tina Kold Jensen Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Blegdamsvej, Copenhagen, Denmark
The International Research Centre in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
Department of Environmental Medicine, Institute of Public Health, University of Southern Denmark, Odense, Denmark

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Niels Erik Skakkebæk Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Blegdamsvej, Copenhagen, Denmark
The International Research Centre in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

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Anders Juul Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Blegdamsvej, Copenhagen, Denmark
The International Research Centre in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

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Anna-Maria Andersson Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Blegdamsvej, Copenhagen, Denmark
The International Research Centre in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

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Objective

Calculating the free testosterone level has gained increasing interest and different indirect algorithms have been suggested. The objective was to compare free androgen index (FAI), free testosterone estimated using the linear binding model (Vermeulen: cFTV) and the binding framework accounting for allosterically coupled SHBG monomers (Zakharov: cFTZ) in relation to cardiometabolic conditions.

Design

A prospective cohort study including 5350 men, aged 30–70 years, participating in population-based surveys (MONICA I–III and Inter99) from 1982 to 2001 and followed until December 2012 with baseline and follow-up information on cardiometabolic parameters and vital status.

Results

Using age-standardized hormone levels, FAI was higher among men with baseline cardiometabolic conditions, whereas cFTV and cFTZ levels were lower compared to men without these conditions as also seen for total testosterone. Men in highest quartiles of cFTV or cFTZ had lower risk of developing type 2 diabetes (cFTV: HR = 0.74 (0.49–1.10), cFTZ: HR = 0.59 (0.39–0.91)) than men in lowest quartile. In contrast, men with highest levels of FAI had a 74% (1.17–2.59) increased risk of developing type 2 diabetes compared to men in lowest quartile.

Conclusion

The association of estimated free testosterone and the studied outcomes differ depending on algorithm used. cFTV and cFTZ showed similar associations to baseline and long-term cardiometabolic parameters. In contrast, an empiric ratio, FAI, showed opposite associations to several of the examined parameters and may reflect limited clinical utility.

Open access
Clara Lundetoft Clausen Center of Research & Disruption of Infectious Diseases, Department of Infectious Diseases, Copenhagen University Hospital – Amager and Hvidovre, Hvidovre, Denmark
Department of Infectious Diseases, Copenhagen University Hospital – Amager and Hvidovre, Hvidovre, Denmark

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Trine Holm Johannsen Department of Growth and Reproduction, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark

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Niels Erik Skakkebæk Department of Growth and Reproduction, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark

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Hanne Frederiksen Department of Growth and Reproduction, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark

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Camilla Koch Ryrsø Department of Pulmonary and Infectious Diseases, Copenhagen University Hospital – Nordsjælland, Hillerød, Denmark
Centre for Physical Activity Research, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark

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Arnold Matovu Dungu Department of Pulmonary and Infectious Diseases, Copenhagen University Hospital – Nordsjælland, Hillerød, Denmark

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Maria Hein Hegelund Department of Pulmonary and Infectious Diseases, Copenhagen University Hospital – Nordsjælland, Hillerød, Denmark

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Daniel Faurholt-Jepsen Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark

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Rikke Krogh-Madsen Department of Infectious Diseases, Copenhagen University Hospital – Amager and Hvidovre, Hvidovre, Denmark
Centre for Physical Activity Research, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark

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Birgitte Lindegaard Department of Pulmonary and Infectious Diseases, Copenhagen University Hospital – Nordsjælland, Hillerød, Denmark
Centre for Physical Activity Research, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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Allan Linneberg Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Center for Clinical Research and Prevention, Copenhagen University Hospital – Bispebjerg and Frederiksberg, Copenhagen, Denmark

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Line Lund Kårhus Center for Clinical Research and Prevention, Copenhagen University Hospital – Bispebjerg and Frederiksberg, Copenhagen, Denmark

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Anders Juul Department of Growth and Reproduction, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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Thomas Benfield Center of Research & Disruption of Infectious Diseases, Department of Infectious Diseases, Copenhagen University Hospital – Amager and Hvidovre, Hvidovre, Denmark
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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Aim

To explore pituitary–gonadal hormone concentrations and assess their association with inflammation, severe respiratory failure, and mortality in hospitalized men and women with COVID-19, and compare these to hormone concentrations in hospitalized patients with bacterial community-acquired pneumonia (CAP) and influenza virus CAP and to concentrations in a reference group of healthy individuals.

Methods

Serum concentrations of testosterone, estrone sulfate, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and interleukin-6 (IL-6) were measured within 4 days of admission. Associations were assessed by logistic regression analysis in patients with COVID-19, and results were reported as odds ratio with 95% CI per two-fold reduction after adjustment for age, comorbidities, days to sample collection, and IL-6 concentrations.

Results

In total, 278 patients with COVID-19, 21 with influenza virus CAP, and 76 with bacterial CAP were included. Testosterone concentrations were suppressed in men hospitalized with COVID-19, bacterial and influenza virus CAP, and moderately suppressed in women. Reductions in testosterone (OR: 3.43 (1.14–10.30), P = 0.028) and LH (OR: 2.51 (1.28–4.92), P = 0.008) were associated with higher odds of mehanical ventilation (MV) in men with COVID-19. In women with COVID-19, reductions in LH (OR: 3.34 (1.02–10-90), P = 0.046) and FSH (OR: 2.52 (1.01–6.27), P = 0.047) were associated with higher odds of MV.

Conclusion

Low testosterone and LH concentrations were predictive of severe respiratory failure in men with COVID-19, whereas low concentrations of LH and FSH were predictive of severe respiratory failure in women with COVID-19.

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Line Tang Møllehave Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, Frederiksberg, Denmark

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Marie Holm Eliasen Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, Frederiksberg, Denmark

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Ieva Strēle The Institute of Occupational Safety and Environmental Health, Riga Stradiņš University, Riga, Latvia

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Allan Linneberg Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, Frederiksberg, Denmark
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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Rodrigo Moreno-Reyes Nuclear Medicine Department, Erasme Hospital, Brussels, Belgium
Université Libre de Bruxelles, Bruxelles, Belgium

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Ludmila B Ivanova Faculty of Medicine, Sofia University St. Kl. Ohridski, Sofia, Bulgaria

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Zvonko Kusić Croatian Academy of Sciences and Arts, Zagreb, Croatia
School of Medicine, Zagreb, Croatia

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Iris Erlund Department of Government Services, Finnish Institute for Health and Welfare, Helsinki, Finland

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Till Ittermann Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany

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Endre V Nagy Division of Endocrinology, Department of Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary

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Ingibjorg Gunnarsdottir Faculty of Food Science and Nutrition, University of Iceland, Reykjavik, Iceland
Department of Clinical Nutrition, Landspitali-National University Hospital, Reykjavik, Iceland

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Jonathan Eli Arbelle Division of Medicine, Maccabi Healthcare Services, Tel Aviv, Israel
Goldman School of Medicine, Ben Gurion University of the Negev, Beer Sheva, Israel

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Aaron Milton Troen The Institute of Biochemistry Food Science and Nutrition, The Hebrew University of Jerusalem, Rehovot, Israel

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Valdis Pīrāgs Internal Medicine, University of Latvia, Riga, Latvia

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Lisbeth Dahl Seafood, Nutrition and Environmental State, Institute of Marine Research (IMR), Bergen, Norway

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Alicja Hubalewska-Dydejczyk Chair and Department of Endocrinology, Jagiellonian University, Medical College, Cracow, Poland

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Malgorzata Trofimiuk-Müldner Chair and Department of Endocrinology, Jagiellonian University, Medical College, Cracow, Poland

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João Jacome de Castro Endocrine Department, Armed Forces Hospital, Lisbon, Portugal

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Mafalda Marcelino Endocrine Department, Armed Forces Hospital, Lisbon, Portugal

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Simona Gaberšček Department of Nuclear Medicine, University Medical Centre Ljubljana, Ljubljana, Slovenia
Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia

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Katja Zaltel Department of Nuclear Medicine, University Medical Centre Ljubljana, Ljubljana, Slovenia
Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia

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Manuel Puig-Domingo Department of Endocrinology and Nutrition, Germans Trias Research Institute and Hospital, Badalona, Spain
Universitat Autònoma de Barcelona, Barcelona, Spain

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Lluis Vila Endocrinology and Nutrition Service, Hospital Moisés Broggi, Sant Juan Despi, Barcelona, Spain

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Sofia Manousou Sahlgrenska Academy, Institute of Medicine, Gothenburg, Sweden
Frölunda Specialist Hospital, Västra Frölunda, Sweden

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Helena Filipsson Nyström Department of Endocrinology, Specialist Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden
Department of Internal Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
Wallenberg Centre of Molecular and Translational Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden

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Michael Bruce Zimmermann Health Sciences and Technology, ETH Zurich, Zurich, Switzerland

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Karen R Mullan Regional Centre for Endocrinology and Diabetes, Belfast Health and Social Care Trust, Belfast, UK

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Jayne Valerie Woodside Centre for Public Health, Queen’s University Belfast, Belfast, UK

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Henry Völzke Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany

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Betina Heinsbæk Thuesen Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, Frederiksberg, Denmark

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Objective

Registers of diagnoses and treatments exist in different forms in the European countries and are potential sources to answer important research questions. Prevalence and incidence of thyroid diseases are highly dependent on iodine intake and, thus, iodine deficiency disease prevention programs. We aimed to collect European register data on thyroid outcomes to compare the rates between countries/regions with different iodine status and prevention programs.

Design

Register-based cross-sectional study.

Methods

National register data on thyroid diagnoses and treatments were requested from 23 European countries/regions. The provided data were critically assessed for suitability for comparison between countries/regions. Sex- and age-standardized rates were calculated.

Results

Register data on ≥1 thyroid diagnoses or treatments were available from 22 countries/regions. After critical assessment, data on medication, surgery, and cancer were found suitable for comparison between 9, 10, and 13 countries/regions, respectively. Higher rates of antithyroid medication and thyroid surgery for benign disease and lower rates of thyroid hormone therapy were found for countries with iodine insufficiency before approx. 2001, and no relationship was observed with recent iodine intake or prevention programs.

Conclusions

The collation of register data on thyroid outcomes from European countries is impeded by a high degree of heterogeneity in the availability and quality of data between countries. Nevertheless, a relationship between historic iodine intake and rates of treatments for hyper- and hypothyroid disorders is indicated. This study illustrates both the challenges and the potential for the application of register data of thyroid outcomes across Europe.

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