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

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


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.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Body Mass Index
  • Genetic Predisposition to Disease
  • Humans
  • Male
  • Mendelian Randomization Analysis*
  • Obesity / blood*
  • Obesity / genetics*
  • Phenotype
  • Polymorphism, Single Nucleotide
  • Testosterone / blood*
  • Young Adult


  • Testosterone

Grant support

This study was supported by the Swedish Research Council and by grants from the Swedish government (under the Avtal om Läkarutbildning och Medicinsk Forskning [Agreement for Medical Education and Research]), the Lundberg Foundation, the Torsten Söderberg Foundation, the Novo Nordisk Foundation and the Knut and Alice Wallenberg Foundation. Data collection in the Inter99 Study was supported economically by The Danish Medical Research Council, The Danish Centre for Evaluation and Health Technology Assessment, Novo Nordisk, Copenhagen County, The Danish Heart Foundation, The Danish Pharmaceutical Association, Augustinus foundation, Ib Henriksen foundation and Becket foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.