Joint growth hormone and cortisol spontaneous secretion is more asynchronous in older females than in their male counterparts

In humans, cortisol and GH are secreted in a pulsatile manner, and an inter action between GH and the hypothalamic-pituitary-adrenal axis has been esta blished. Ln view of the sexually dimorphic pattern in GH secretion, we inve stigated the GH-cortisol bihormonal secretory dynamics in male and female h ealthy older individuals. We studied the GH and cortisol secretory patterns in 83 healthy subjects (45 men and 38 women; age range, 59.4-73.0 yr) by d etermining serum GH and cortisol concentrations at 20-min intervals for 24 h. The irregularity of GH and cortisol secretion was assessed using approxi mate entropy (ApEn), a scale- and model-independent statistic. The synchron y of joint GH-cortisol spontaneous secretion was quantified using the cross -ApEn statistic. Cross-correlation analysis of GH and cortisol patterns was computed at various time lags covering the 24-h period. Mean 24-h serum GH concentrations were significantly higher in females (mea n, 1.31mU/L; sn, 0.87) than in males (mean, 0.88 mU/L; so, 0.42; P = 0.009) , whereas mean 24-h serum total cortisol concentrations were higher in male s (mean, 9.0 mug/dL; SD, 1.4) than in females (mean, 7.3 mug/dL; so, 1.4;P = 0.0001). GH secretion was more irregular in females (mean ApEn, 0.81; sn, 0.23) than in males (mean ApEn, 0.60; so, 0.20; P < 0.001). No significant difference in the regularity of cortisol secretion was noted between sexes . Cross-ApEn values of paired GH-cortisol were higher in females (mean, 1.1 5; sn, 0.18) than in males (mean, 1.01; sn, 0.16; P = 0.0003). Stepwise mul tiple linear regression analysis indicated that estradiol and insulin-like growth factor-binding protein-3 concentrations were independently related t o GH ApEn values (P = 0.14; P = 0.01), whereas cross-ApEn values of paired GH-cortisol were best predicted by FSH concentrations (r(2) = 0.37; P = 0.0 03). Cross-correlation analysis revealed a significant positive correlation between GH and cortisol, peaking at lag time of 4.7 h in males (r = 0.30; P < 0.0001) and 4.3 h in females (r = 0.14; P < 0.0001), with GH leading co rtisol by these time intervals. In addition, a significant negative correla tion between the two hormones was noted over time, peaking at 4.7 h in male s (r = -0.21; P < 0.0001) and 6.3 h in females (r = -0.25; P < 0.0001), wit h cortisol leading GH by these time intervals. The above results indicate that in the elderly, females have a more disorde red GH secretory pattern and a more asynchronous joint GH-cortisol secretio n than their male counterparts. These observations most likely reflect bidi rectional interactions between the GH and hypothalamic-pituitary-adrenal ar ds in humans as well as diminution of subsystem integrity and synchronous c ontrol of interconnected hormonal systems with advancing age.