Background: Effects of endogenous and exogenous testosterone (T) on glycemia (HbA1c) and erythrocyte lifespan (EL) are controversial. Three major placebo-controlled RCTs of testosterone treatment (T Trials, T4DM, TRAVERSE) all concluded that T treatment did not alter chronic glycaemia (HbA1c) despite T4DM showing reduced acute/short-term measures of glycemia such as fasting glucose, T2DM diagnosis by GTT, reduced glycosylated albumin but not oxidized glucose (1,5-anhydroglucitol). One hypothesis is that T treatment extended EL and thereby increased HbA1c. We reported that T treatment of hypogonadal (n=5) and trans (n=9) men had reduced baseline EL vs healthy controls (n=9) with EL increased at 6 weeks but back to baseline by 18 weeks of T treatment (McMartin et al, 2024). We now expand this study to including more healthy controls and T-treated hypogonadal and trans men to determine if the apparently shorter EL of hypogonadal males is rectified by T treatment.

Methods: EL was determined by carbon monoxide breath test as described (1) with haematological variables measured by autoanalyser. Data analysis was by ANOVA/ANCOVA using NCSS 2026 software.

Results: EL did not differ between healthy male controls ((n=26, 89± 3 days) and hypogonadal (primary, n=38, 85± 4 days; secondary, n=11, 87 ± 8 days) or trans (n=70, 84 ± 3 days) men despite trans men having higher hemoglobin and hematocrit but without differences in serum T between groups. Adjustment for significant covariables (age, older hypogonadal men than healthy controls or trans men; height, shorter trans men than other males) did not change the overall EL findings.

Conclusion: We conclude that exogenous or endogenous T exposure in healthy, hypogonadal or trans men does not modify EL. The previous finding of a short-term increase in EL on initiation of T treatment may reflect the transient effect of T in stimulating short-lived reticulocytes and/or insufficient healthy controls.