Testosterone, risk, and socioeconomic position in British men: Exploring causal directionality

Lower testosterone levels in men are observationally associated with worse health, but it is unclear whether they contribute to well-established social gradients in health. Mendelian Randomization studies suggest positive testosterone-health associations may not be causal, with some intervention studies suggesting testosterone administration could be harmful. Since testosterone is rarely measured in general population studies, very little is known about how testosterone varies by social position. Differences by education and household income in British men aged 60-64y were recently reported, but it is unclear whether this reflects an influence of socioeconomic position (SEP) on testosterone, influence of testosterone on SEP, or confounding. In the UK Household Longitudinal Study, a nationally-representative survey of UK adults, we examine social differences in testosterone in 3663 men aged 16-97y in 2010-12. We consider diverse dimensions of SEP: education, employment status, equivalized household income and personal earnings. Multivariable regression is used to explore social differences in testosterone across the adult life-span (16-97y). Secondly, Mendelian Randomization (MR), an approach which uses gene variants as instrumental variables for endogenous exposures, is used to investigate causal directionality. We examine associations with risk-taking, a plausible mediator of testosterone-SEP associations. In observational models no social differences in testosterone are seen, but MR models suggest a positive influence of testosterone on earnings (increase in log-transformed monthly earnings (GBP) per standard deviation increase in testosterone: 0.51, 95%CI: 0.03,1.05, p = 0.07) and probability of being in work (probit coefficient:0.25, 95%CI: 0.01,0.51, p = 0.06). Though MR estimates are less precise, results are consistent with previous literature linking testosterone with labour market success. The discrepancy may reflect suppression of observational associations by factors positively correlated with testosterone and negatively correlated with SEP, or indicate an influence of typical lifetime testosterone, which may be better indexed by genetic variants than by single testosterone measurements subject to noise.