Causal relationship between obesity and serum testosterone status in men: A bidirectional mendelian randomization analysis

Research output: Contribution to journalArticle


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.


  • Joel Eriksson
  • Robin Haring
  • Niels Grarup
  • Liesbeth Vandenput
  • Henri Wallaschofski
  • Erik Lorentzen
  • Torben Hansen
  • Dan Mellström
  • Oluf Pedersen
  • Matthias Nauck
  • Mattias Lorentzon
  • Lise Lotte Nystrup Husemoen
  • Henry Völzke
  • Magnus Karlsson
  • Sebastian E. Baumeister
  • Allan Linneberg
  • Claes Ohlsson
External organisations
  • Monash University
  • University of Gothenburg
  • Research Centre for Prevention and Health
  • Skåne University Hospital
  • University of Regensburg
  • Copenhagen University Hospital
  • University Medicine Greifswald
  • University of Copenhagen
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Endocrinology and Diabetes
  • Public Health, Global Health, Social Medicine and Epidemiology
Original languageEnglish
Article numbere0176277
JournalPLoS ONE
Issue number4
Publication statusPublished - 2017 Apr 1
Publication categoryResearch