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PLoS One. 2017 Apr 27;12(4):e0176277. doi: 10.1371/journal.pone.0176277. eCollection 2017.

Causal relationship between obesity and serum testosterone status in men: A bi-directional mendelian randomization analysis.

Author information

1
Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
2
University Medicine Greifswald, Institute of Clinical Chemistry and Laboratory Medicine, Greifswald, Germany.
3
School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia.
4
The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
5
Bioinformatics Core Facility, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
6
Geriatric Medicine, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
7
Research Centre for Prevention and Health, the Capital Region, Copenhagen, Denmark.
8
University Medicine Greifswald, Institute for Community Medicine, Greifswald, Germany.
9
Clinical and Molecular Osteoporosis Research Unit, Department of Orthopaedics and Clinical Sciences, Lund University, Skåne University Hospital (SUS), Malmö, Sweden.
10
Department of Epidemiology and Preventive Medicine, University of Regensburg, Regensburg, Germany.
11
Department of Clinical Experimental Research, Rigshospitalet, Glostrup, Denmark.
12
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Abstract

CONTEXT:

Obesity in men is associated with low serum testosterone and both are associated with several diseases and increased mortality.

OBJECTIVES:

Examine the direction and causality of the relationship between body mass index (BMI) and serum testosterone.

DESIGN:

Bi-directional Mendelian randomization (MR) analysis on prospective cohorts.

SETTING:

Five cohorts from Denmark, Germany and Sweden (Inter99, SHIP, SHIP Trend, GOOD and MrOS Sweden).

PARTICIPANTS:

7446 Caucasian men, genotyped for 97 BMI-associated SNPs and three testosterone-associated SNPs.

MAIN OUTCOME MEASURES:

BMI and serum testosterone adjusted for age, smoking, time of blood sampling and site.

RESULTS:

1 SD genetically instrumented increase in BMI was associated with a 0.25 SD decrease in serum testosterone (IV ratio: -0.25, 95% CI: -0.42--0.09, p = 2.8*10-3). For a body weight reduction altering the BMI from 30 to 25 kg/m2, the effect would equal a 13% increase in serum testosterone. No association was seen for genetically instrumented testosterone with BMI, a finding that was confirmed using large-scale data from the GIANT consortium (n = 104349).

CONCLUSIONS:

Our results suggest that there is a causal effect of BMI on serum testosterone in men. Population level interventions to reduce BMI are expected to increase serum testosterone in men.

PMID:
28448539
PMCID:
PMC5407807
DOI:
10.1371/journal.pone.0176277
[Indexed for MEDLINE]
Free PMC Article

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