Bibian van der Voorn

141 GENDER-SPECIFIC HPA AXIS ACTIVITY IN CHILDHOOD BACKGROUND The hypothalamus-pituitary-adrenal (HPA) and hypothalamus-pituitary-gonadal (HPG) axes are closely connected. Animal studies demonstrated that CRH inhibits the HPG axis at all levels, while testosterone inhibits the HPA axis at the hypothalamic level. Additionally, estrogens stimulate the HPA axis at both the hypothalamic and adrenal levels. Moreover, CRH levels were dependent on the phase of the menstrual cycle, with the highest concentrations occurring during the follicular phase 1,2 . Human studies suggested that estrogens decrease the hepatic A-ring reduction of cortisol, albeit not in the short term 3 , and increase the production of CBG, thereby affecting the bioavailability of cortisol 1,4,5 . The latter being enhanced by the use of oral contraceptives. Furthermore, HPA axis responses to acute psychological stress were different depending on the phase of the menstrual cycle 2,4 . Due to an increase in sex steroid concentrations, gender differences in HPA axis activity have been postulated to emerge during puberty 6,7 . However, more recent evidence suggests that gender differences in HPA axis activity are already present early in life 1,8,9 . Putative mediators of these prepubertal gender differences are the postnatal reproductive hormone surge, also known as mini-puberty 10 , and sex- specific effects of styles in parental care, such as psychosocial stress reactivity to maternal over-controlling behavior 11 . However, physiological gender differences in cortisol concentrations during childhood have not been studied yet. Therefore, the question was raised whether gender differences in unstimulated HPA axis activity emerge during puberty or whether they are already present earlier in life. Accordingly, we conducted a systematic review andmeta-analysis with the hypothesis that gender-specific differences in unstimulated HPA axis activity are present in early life and are subsequently influenced by puberty. METHODS SEARCH STRATEGY From inception up to 14 January 2016, PubMed and Embase.com were searched (by BvdV and JCFK) for studies that reported non-stimulated cortisol in serum or saliva, or cortisol in 24h-urine for healthy boys and girls aged ≤18 yr separately.