Significant ethnic variation in circulating total bound and free testosterone
AH Heald1, F Bethell2, S Anderson3, D Owen2, I Laing2, JM Gibson1 & JK Cruickshank3
OBJECTIVE Measurement of serum testosterone level is an integral part of the assessment of men presenting to endocrine clinics. Little is known about variation of testosterone level by ethnic group. The principal determinant of testosterone bioavailability is sex hormone binding globulin (SHBG) which itself is a marker for insulin sensitivity. Our aim was to examine variations in testosterone and SHBG levels across three ethnic groups in relation to ethnic differences in insulin sensitivity.
DESIGN Males of three different ethnic groups living in Manchester, UK were sampled. These were of European (n=55), Pakistani (n=75) and African-Caribbean (AfC) origin (n=50). Circulating testosterone and SHBG concentrations were measured and free testosterone calculated by Vermeulen's method. Insulin sensitivity (HOMA-S) was determined from paired fasting plasma intact insulin and glucose values.
RESULTS Testosterone levels were lower in Pakistani men (14.6 (12.6-16.6))nM (mean with 95% CI) than Europeans (18.7 (16.8-20.6))nM or AfCs (18.0 (16.4-19.6))nM (F=4.8, p=0.009). Despite SHBG levels being lower in Pakistani men (22.9 (19.4-26.5))nM compared with Europeans (28.7 (25.7-31.8))nM and AfCs (26.9 (23.9-30.0))nM (F=3.0, p<0.05), circulating free testosterone was lower in the Pakistani group (367 (326-408))pM than Europeans (455 (416-494))pM or AfCs (458 (424-492))pM (F=6.8, p=0.001).
Pakistani men were on average 4cm shorter than other groups. However the lower free testosterone persisted even when corrected for height. Lower SHBG in the Pakistani men was paralleled by a lower HOMA-S (0.40 (0.25-0.56)) compared with Europeans (0.77 (0.61-0.93)) and AfCs (0.80 (0.66-0.93)) F=8.2, p<0.0001) and lnSHBG correlated positively with lnHOMA-S (r = 0.26, p<0.001)). As expected lnSHBG correlated strongly with total testosterone (r = 0.40, p<0.001).
Both total bound and bioavailable testosterone were lower in Pakistani males. SHBG levels were also lower in Pakistani men, in keeping with their poorer insulin sensitivity. Whether ethnic specific normal ranges for testosterone would be useful in clinical practice will require further work.