Bibian van der Voorn

181 GENDER-SPECIFIC HPA AXIS REACTIVITY IN CHILDHOOD DISCUSSION In this systematic review, we found that sex differences in HPA axis reactivity are suggested to be present in childhood. In general, with regard to diurnal rhythm, the CAR and social stress tests, around 50% of the studies, notably the larger ones, found sex differences, of which approximately 80% found a more variable diurnal rhythm, a higher CAR, and/or a stronger cortisol response to social stress tests in girls, suggestive of a more variable HPA axis. We found no evidence for a sex difference in cortisol response after a pharmacological challenge, with only two out of seven studies reporting a higher cortisol response in boys. Findings from studies addressing sex differences in cortisol response after miscellaneous (social or physical) stress tests were inconsistent, due to different types of stressors applied. In total, 12 out of 29 studies found a more variable diurnal rhythm in girls, while 2 found this in boys and 15 did not find sex differences. A higher CAR in girls was found in 8 out of 18 studies, although 1 study found a higher CAR in boys and 9 studies found no sex differences. Girls had a stronger cortisol response to social stress tests in 9 out of 21 studies, whereas boys had a stronger response in 4 studies and no sex differences were found in 8 studies. Therefore, although results are suggestive of a more responsive HPA axis in girls during childhood, these results must be interpreted with caution as the evidence is not unequivocal. However, the sample sizes of the studies that found sex differences were on average larger, while the studies that did not find sex differences more often had a sample size <100. Our results differed considerably with findings from studies in adults. Notably, psychological stress studies in adults either found no gender difference or a more pronounced cortisol response in men. 4 This difference might be explained by gonadal hormones, more specifically estrogens. In childhood, as we have shown in this review, cortisol reactivity appears to be more pronounced in females. However, other research has shown that in adults, females were found to exhibit attenuated cortisol responses to stress, and males displayed a higher cortisol reactivity. 4 Consequently, it could be hypothesized that post-menopausal women once again show a stronger cortisol response to stress compared to men of the same age. Otte et al. (2005) 5 , who performed a meta-analysis to evaluate and quantify age-related changes in cortisol response, found a three-fold higher increase in cortisol reactivity with aging inwomen compared to men. However, studies examining cortisol reactivity in elderly subjects are inconclusive with regard to gender differences. 93-96