Longitudinal changes in serum testosterone and sex hormone‐binding globulin in ageing men

Marriott, R.J., Murray, K., Hankey, G.J., Manning, L., Dwivedi, G., Wu, F.C.W., Yeap, B.B., 2022. Longitudinal changes in serum testosterone and sex hormone‐binding globulin in men aged 40–69 years from the UK Biobank. Clinical Endocrinology 96, 589–598. doi:10.1111/cen.14648

The inevitability of a decline in circulating testosterone levels with age has become dogma despite insufficient supporting data^[1]. The belief that testosterone levels fall as a consequence of aging, combined with rising acceptance of testosterone treatment for non-pathological states, has led to increasing use of testosterone treatment by people who may not need it and may be harmed by it^[2] and has sparked a number of internet-based businesses marketing testosterone direct to the public.

There are two principal challenges in accurately identifying the effect of aging on testosterone levels. The first is obtaining longitudinal measures of circulating testosterone. There are many studies that compare concentrations between men of different ages but there is considerable variation in testosterone levels between individuals, and repeated samples from the same people at different ages are preferred.

The other challenge to assessing the effects of aging on testosterone levels is the accumulation of exposures to factors that might affect circulating concentrations (such as environmental toxins) and the development of chronic disease. It is necessary to separate the effects of the increasing severity and incidence of illness that accompanies aging, from the (potential) effects of aging itself.

Marriot and colleagues have examined longitudinal measures of serum testosterone in thousands of healthy men aged 40-69 years, from the UK Biobank^[3], and found no change with advancing age^[4]. Men’s testosterone levels varied very little from their initial value when measurements were repeated after an interval of 2.3-6.1 years.

The study by Marriot and colleagues does not have a long follow-up period. Previous longitudinal studies with longer follow-up periods show declines in testosterone levels ranging between 1-2% per year, so following UK Biobank subjects for longer might reveal a gradual change with age. However, the sample numbers in most other studies are relatively small, as are the reported effect sizes, and there are other factors that suggest the findings should be interpreted with caution^[5].

Some previous studies of aging and testosterone have highlighted the effect of poor health on declining testosterone levels^1,[6] and shown that improvements in health with age are associated with rising testosterone levels and vice versa^[7]. A negative effect of obesity on testosterone concentrations is demonstrated by (age-specific) reference ranges for non-obese European and American men that are higher than for all men (based on data from the Framingham Heart Study, European Male Aging Study, Osteoporotic Fractures in Men Study, and Male Sibling Study of Osteoporosis)^[8].

Despite all the data from all of the men in all of the studies so far, we still don’t know whether men’s testosterone levels fall naturally with aging. There is sufficient knowledge, though, for men to be reassured that maintaining their health as they age makes a decline in testosterone less likely.