The association between serum testosterone and insulin resistance: a longitudinal study

Abstract

The objective of this study was to investigate whether there is a bidirectional association between testosterone concentrations and insulin resistance, in a prospective population study. A random population sample of 1400 men, aged 30–74, was examined in 2002–2005 in southwestern Sweden and followed up in 2012–2014 (N = 657). After excluding subjects without information on sex hormones and insulin resistance, 1282 men were included in the baseline study. Fasting measurements of plasma glucose, insulin and hormones were performed. Insulin resistance was defined using HOMA-Ir. Mean age at baseline was 47.3 ± 11.4 years. From the follow-up survey 546 men were included, mean age 57.7 ± 11.6 years. Low concentrations of total testosterone at baseline were significantly associated with high logHOMA-Ir at follow-up in a multivariable model including age, waist–hip ratio, physical activity, alcohol intake, smoking, LDL, CRP, hypertension, diabetes and logHOMA-Ir at baseline as covariates (β = −0.096, P = 0.006). Similar results were observed for bioavailable testosterone. Men within the lowest quartile of total testosterone at baseline had significantly higher logHOMA-Ir at follow-up than other quartiles (Q1 vs Q2 P = 0.008, Q1 vs Q3 P = 0.001, Q1 vs Q4 P = 0.052). Multivariable analysis of the impact of insulin resistance at baseline on testosterone levels at follow-up revealed no significant associations regarding testosterone concentrations (β = −0.003, P = 0.928) or bioavailable testosterone (β = −0.006, P = 0.873), when adjusting for baseline concentrations of total testosterone, age, waist–hip-ratio, LDL, CRP, physical activity, alcohol intake, smoking, hypertension and diabetes. Low testosterone concentrations at baseline predicted higher insulin resistance at follow-up, but high insulin resistance at baseline could not predict low testosterone at follow-up.

Sex hormones, adiposity, and metabolic traits in men and women: a Mendelian randomisation study

“…These results are congruent with previous MR studies in the UKBB showing positive links between higher BioT and increased lean mass ( 24 , 48 ), reduced fat mass ( 48 ), and lower glucose ( 24 ). However, they are only partly consistent with observational data demonstrating inverse associations between circulating testosterone and risk of metabolic syndrome in men ( 31 , 32 , 49 , 50 , 51 ), as well as clinical findings in men with physiologic or chemically induced hypogonadism, who were shown to be at increased risk of developing obesity and IR, as well as T2DM ( 8 , 52 , 53 ). On the other hand, our data are aligned with RCTs of testosterone therapy in men, which reported benefits on adiposity as reflected by lower HIPadjBMI herein, as well as diminished fasting glucose levels and T2D risk ( 54 , 55 ).…”

Male hypogonadism and pre-diabetes interplay: association or causal interaction? A systematic review

“…Overall, a bidirectional association between male hypogonadism and pre-diabetes has been identified [72,73] .…”

Late‐onset hypogonadism: metabolic impact

“…Consistent with earlier work, in a recent prospective study of 141 younger (mean age 43 years) mostly insulin resistant men, insulin resistance (measured using an octreotide‐based pancreatic suppression test) predicted hypogonadism (defined as a total testosterone < 10.4 nmol/L) somewhat more strongly (risk ratio = 2.2) than hypogonadism predicted insulin resistance (risk ratio = 1.3) ( p = 0.03) (Contreras et al ., 2018). However, in a larger prospective study among 1400 Swedish men (mean age 58 years), low baseline testosterone predicted insulin resistance (measured by HOMA‐IR), but high insulin resistance at baseline did not predict low testosterone at follow‐up (Ottarsdottir et al ., 2018). Although observational studies, even if prospective cannot establish causality, nor determine the direction of causality, the evidence overall is consistent with a bidirectional relationship.…”