HPA axis responses to laboratory psychosocial stress in healthy elderly adults, younger adults, and children: impact of age and gender

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Abstract

Data from five independent studies were reanalyzed in order to investigate the impact of age and gender on HPA axis responses to an acute psychosocial laboratory stress task. The total sample consisted of 102 healthy subjects with 30 older adults (mean age: 67.3 y), 41 young adults (mean age: 23.5 y), and 31 children (mean age: 12.1 y). All participants were exposed to the Trier Social Stress Test (TSST).

The stress protocol caused highly significant ACTH and total plasma cortisol responses in older and younger male and female adults (all p<0.0001) as well as salivary free cortisol responses in all six age and gender groups (all p<0.0001). Three-way ANOVAs for repeated measurement were applied to investigate the impact of age and gender on ACTH and cortisol responses. Results showed that the ACTH response to stress was higher in younger adults compared to older adults (main effect: p=0.009, interaction: p=0.06). Post hoc analyses revealed that there was no age effect in the subgroup of women (p=n.s.), while younger men had higher ACTH responses compared to older men (p=0.01). For total plasma cortisol, ANOVA results showed that the pattern of reactivity did not differ between age and gender groups (all interactional effects p=n.s.), although older females had hightened overall cortisol levels compared to the other groups, as proofed in post hoc analyses (all p<0.05). For free salivary cortisol, a significant main effect of gender (p=0.05) and an almost significant three-way-interaction (p=0.09) emerged. Post hoc analyses showed an elevated overall free salivary cortisol response in elderly men compared to elderly women (p=0.006), while no gender differences emerged in neither young adults nor children (both p=n.s.).

In sum, the stressor induced significant HPA axis responses in all age and gender groups. The observed ACTH response patterns in young and elderly adults may suggest that a heightened hypothalamic drive in young men decreases with age, resulting in similar ACTH responses in elderly men and women. Alternative interpretations are also discussed. The data also supports the idea of a greater adrenal cortex sensitivity to ACTH signals in young females. Free salivary cortisol responses were elevated in elderly men compared to elderly women, an effect which cannot be explained by gender differences in perceived stress responses to the TSST. It can be speculated if corticosteroid binding globulin (CBG) and/or sex steroids are important modulators of these effects.

Introduction

Although it is known from animal as well as human studies that there exist age-related alterations in hypothalamic–pituitary–adrenal (HPA) axis regulation, it still remains an open question whether stress-related HPA axis functioning alters significantly with age.

While in humans there are only little differences in daytime basal ACTH and cortisol levels (Seeman and Robbins, 1994, Gotthardt et al., 1995, Kudielka et al., 1999, Kudielka et al., 2000), the circadian rhythm seems to advance with age and diurnal amplitudes appear to flatten (Sherman et al., 1985, Van Coevorden et al., 1991, Deuschle et al., 1997). Primarily, cortisol concentrations show age-related changes during night-time at the circadian trough of HPA activity (Van Cauter et al., 1996).

Human studies which apply psychological stress protocols in young and elderly subjects simultaneously are rare. While a study from Gotthardt et al. (1995) report on a significant age effect (with older subjects showing larger cortisol stress responses) two other studies did not show age-related changes in HPA axis functioning neither in men nor in women (Kudielka et al., 1999, Kudielka et al., 2000). In contrast, a fourth study report that the cortisol responses to provoked stress were higher in premenopausal women compared to postmenopausal women (Lindheim et al., 1992), whereas another study only evoked minor HPA axis stress responses in a laboratory setting (Nicolson et al., 1997).

Concerning the impact of gender, human stress studies revealed that there are (a) no significant gender differences or (b) higher cortisol responses in young men compared to young women (Collins and Frankenhaeuser, 1978, Frankenhaeuser et al., 1978, Frankenhaeuser et al., 1980, Forsman and Lundberg, 1982, Lundberg, 1983, Polefrone and Manuck, 1987, Stoney et al., 1987, Kirschbaum et al., 1992, Kirschbaum et al., 1995). In a recent paper, Kirschbaum and coworkers disclosed that the effect of gender is masked in total plasma cortisol stress responses, while significant gender differences emerge for ACTH and free salivary cortisol (Kirschbaum et al., 1999). The study showed that ACTH responses are elevated in men compared to women, regardless of menstrual cycle phase or use of oral contraceptives. Women in the luteal phase have comparable saliva cortisol stress responses compared to men whereas women in the follicular phase or taking oral contraceptives show significantly lower free cortisol responses. These observations point at the necessity to strictly distinguish between the total cortisol secretion and the bioavailable cortisol levels. The same gender effect with higher ACTH and free salivary cortisol emerged for elderly subjects, as shown by Kudielka et al. (1998). In contrast, Seeman et al. (1995) reported on a higher cortisol reactivity in elderly women compared to elderly men employing a driving simulation challenge. Recently, these observations were corroborated using a 30-min cognitive challenge paradigm by the same group (Seeman et al., 2001).

Human studies investigating the impact of age and gender on HPA axis responses after psychological stress are still rare and results remained contradictory. Therefore, the present reanalysis aims to contribute to the question of age and gender effects on HPA axis stress responses including healthy male and female elderly adults, young adults, as well as children.

Section snippets

Subjects

Data for the present reanalysis originally come from five independent studies conducted by Kudielka et al., 1999, Kudielka et al., 2000, Kirschbaum et al., 1999, Buske-Kirschbaum et al., 1997, and Buske-Kirschbaum et al. (unpublished data). All participants had reported to the laboratory at least twice. At a first appointment, all volunteers underwent a medical examination to identify healthy individuals and patients suffering from specific diseases. Volunteers with psychiatric, endocrine,

ACTH (only older and younger adults)

First of all, the applied three-way ANOVA for ACTH resulted in a significant main effect of time (F(3,183)=56.12, p<0.0001) and age (F(1,61)=7.35, p<0.009). Furthermore, the main effect of gender (F(1,61)=3.12, p<0.08) and the two-way interactions ‘age by time’ (F(1.2,72.1)=3.44, p<0.06) and ‘gender by time’ (F(1.2,72.1)=3.11, p<0.08) approached the level of significance.

In order to clarify whether all different groups had a significant ACTH response, one-way repeated measurement ANOVAs for

Discussion

The present data show that the psychosocial stress protocol TSST (Trier Social Stress Test) induced significant HPA axis responses in male and female elderly adults, younger adults, as well as children. Therefore, the TSST as described by Kirschbaum, Pirke, and Hellhammer a decade ago (1993) can be considered as a valid psychosocial stress protocol in laboratory settings in a wide range of age groups in both sexes. This observation is strongly supported by a recently conducted independent

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