Familial Longevity Is Not Associated with Major Differences in the Hypothalamic-Pituitary-Gonadal Axis in Healthy Middle-Aged Men.

Context: A trade-off between fertility and longevity possibly exists. The association of the male hypothalamic-pituitary-gonadal (HPG) axis with familial longevity has not yet been investigated.

Objective: To study 24-h hormone concentration profiles of the HPG axis in men enriched for familial longevity and controls.

Design: We frequently sampled blood over 24 h in 10 healthy middle-aged male offspring of nonagenarian participants from the Leiden Longevity Study together with 10 male age-matched controls. Individual 24-h luteinizing hormone (LH) and testosterone concentration profiles were analyzed by deconvolution analyses to estimate secretion parameters. Furthermore, the temporal relationship between LH and testosterone was assessed by cross-correlation analysis. We used (cross-)approximate entropy to quantify the strength of feedback and/or feedforward control of LH and testosterone secretion.

Results: Mean [95% confidence interval (CI)] total LH secretion of the offspring was 212 (156-268) U/L/24 h, which did not differ significantly ( = 0.51) from the total LH secretion of controls [186 (130-242) U/L/24 h]. Likewise, mean (95% CI) total testosterone secretion of the offspring [806 (671-941) nmol/L/24 h] and controls [811 (676-947) nmol/L/24 h] were similar ( = 0.95). Other parameters of LH and testosterone secretion were also not significantly different between offspring and controls. The temporal relationship between LH and testosterone and the strength of feedforward/feedback regulation within the HPG axis were similar between offspring of long-lived families and controls.

Conclusion: This relatively small study suggests that in healthy male middle-aged participants, familial longevity is not associated with major differences in the HPG axis. Selection on both fertility and health may in part explain the results.