The impact of normal variation in testosterone levels on health is smaller than commonly assumed
Testosterone is the main male sex hormone, but it is essential for both men and women. Since its discovery in the early 20th century, the hormone has been connected to health, behavior and appearance. In coffee-table discussions, testosterone levels have been taken for granted as an explanation for differences between men and women, for example.
In a recent study, Taru Tukiainen's team at the University of Helsinki wanted to find out to what extent different characteristics are a consequence of variable adult testosterone levels.
The results showed that hereditary differences in adult testosterone levels influenced factors such as haemoglobin levels, female reproductive health, hormonal cancers and hair growth typical for males. However, while the observed associations to different diseases were often clear, variation in testosterone levels alone explained only a fraction of the population level risk for most traits.
The study also found evidence that testosterone levels are likely not the main cause of metabolic diseases such as type 2 diabetes, but rather reflect overall health status.
Biobanks made the huge research sample possible
The team drew on two large biobank datasets, the UK Biobank and the FinnGen study, which together covered more than 625,000 individuals.
First, the research team used the UK biobank data to generate a genetic risk score that is highly predictive of average testosterone levels. Next, they examined the association of this genetic profile with various diseases and traits associated with testosterone.
“Using the biobank data, we were able to test whether individuals with higher hereditary testosterone levels have an increased risk of developing various diseases. We ourselves were surprised at how few clear connections were found," says Jaakko Leinonen, a Postdoctoral Researcher at the Institute for Molecular Medicine Finland (FIMM) at the University of Helsinki, who conducted the study.
Since testosterone has been linked to behaviour, the researchers were also looking for a possible link to neurological and psychiatric diseases. Although the study suggested that hormonal factors may also contribute to such traits, only a few statistically significant associations were found.
The happy medium also applies to testosterone
The amount of testosterone in the body is an individual trait, largely dictated by hereditary factors. However, as is characteristic of hormones, testosterone levels can fluctuate over time according to situation and need. This study focused on the effects of variable baseline testosterone levels between individuals over time.
Although in general the genetic variation that increases testosterone levels had both negative and positive effects in both sexes, the study found that the negative effects on women's health were pronounced.
“Our results suggest that although testosterone is important for both men and women, higher testosterone levels may have more positive effects for men. It is important to note, however, that this is only true for normal biological variation. In women, higher levels are often disadvantageous for reproductive health, for example," says group leader Taru Tukiainen.
Original publication:
Genetic analyses implicate complex links between adult testosterone levels and health and disease. Jaakko T. Leinonen, Nina Mars, Leevi E. Lehtonen, Ari Ahola-Olli, Sanni Ruotsalainen, Terho Lehtimäki, Mika Kähönen, Olli Raitakari, FinnGen Consortium, Terhi Piltonen, Mark Daly, Tiinamaija Tuomi, Samuli Ripatti, Matti Pirinen, Taru Tukiainen. Communications Medicine 2023. DOI: 10.1038/s43856-022-00226-0
Further reading:
Understanding the Health Impacts of Your Genetically Determined Testosterone Levels (Nature Portfolio Health Community Blog post by Jaakko Leinonen)
More information:
Postdoctoral Researcher Jaakko Leinonen
Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki
Group Leader Taru Tukiainen
tel. +358-400-911982
Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki