Increased circulating levels of sex hormone regulator SHBG could be linked to a reduced risk of asthma, particularly in women, a new study has shown.
It is the first time that evidence has been found to demonstrate that sex hormone levels could have a role in explaining the observed gender difference in asthma prevalence.
Researcher at the University of Bristol, England, used measurements of SHBG and total testosterone, taken every two years from 513 boys from the age of nine to 17 who participated in the Children of the 90s Study (ALSPAC), which has been tracking the health of thousands of people born in the Avon region of England since 1991-2.
Information on asthma symptoms was supplied by the boys’ mothers when they were aged 10 and 13, and by the participants themselves at the ages of 16 and 22.
The researchers then pooled genetic data on asthma from more than 460,000 participants in the UK Biobank and the Trans National Asthma Genetics Consortium, applying Mendelian randomisation.
The observational data indicated that higher levels of circulating testosterone in teen boys were weakly associated with lower asthma risk, but no strong links were evident for SHBG levels.
The genetic data, however, indicated that higher levels of SHBG were associated with about 14% lower odds of asthma, although this effect was mostly seen in women.
The findings are published in the latest online edition of Thorax.
“Although previous hypotheses have suggested an immunological/inflammatory effect of SHBG on asthma, Mendelian randomisation does not distinguish between which mechanistic pathways link the exposure to the outcome. Therefore, any indication of SHBG’s causality does not imply a biological or immunological effect of sex hormones,” say the researchers.
In a linked podcast, lead author Dr Ryan Arathimos, said: “We found a protective effect of increased SHBG on asthma and observed that this was stronger in females. But we couldn’t distinguish whether the effect was sex specific – so if the effects of SHBG on asthma only exist in females – and our study design didn’t permit us to say if the protective effects of SHBG are in childhood, puberty, or adult life.
“We don’t know exactly which hormone or combination of hormones, be it testosterone or oestrogen, is having the effect on asthma, so further work is definitely required to disentangle the pathways involved.”
Arathimos R, Granell R, Haycock P et al. Genetic and observational evidence supports a causal role of sex hormones on the development of asthma. Thorax 2 April 2019; doi 10.1136/thoraxjnl-2018-212207.
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