***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Levels of the stress-sensitive hormone cortisol increase dramatically in the first 30 - 40min after waking , an effect known as the  cortisol awakening response ( CAR ) . There is considerable cross-sectional evidence that psychosocial stress is associated with an increased CAR , and the CAR has been found to be altered in the presence of stress-related diseases , including major depressive disorder ( MDD ) . To date , no prospect i ve longitudinal studies have examined whether individual differences in the CAR serve as a premorbid risk factor for MDD . In a sample of 230 late adolescents , clinical diagnoses of MDD were predicted from the CAR as well as other indicators of basal cortisol functioning gathered 1 year earlier , including : waking cortisol levels , bedtime cortisol levels , the size of the CAR , average cortisol , and the slope of the diurnal cortisol rhythm across the waking day . Age and gender , health and health behaviors , baseline neuroticism , exposure to stressful life events and past episodes of mood and anxiety disorders were included as covariates , to help ensure effects are attributable to the CAR rather than related variables . A higher baseline CAR was associated with a significantly increased risk of developing MDD by follow-up , even when excluding individuals with baseline MDD . No other baseline cortisol measures were significant prospect i ve predictors of MDD . In summary , the  CAR  is a significant prospect i ve risk factor for the development of MDD in young adults , providing some support for the possibility that a heightened CAR may play a role in the etiology of major depressive disorder BACKGROUND Sex differences in stress responses may be one mechanism underlying gender differences in depression . We hypothesized that men and women would show different adrenocortical responses to different stressors . In particular , we predicted that women would show greater responses to social rejection stressors , whereas men would demonstrate greater responses to achievement stressors . METHODS Following a rest session in which they habituated to the laboratory , 50 healthy volunteers ( 24 men and 26 women , mean age 19.1 , SD = 1.13 ) were r and omly assigned to achievement or rejection stress conditions . The achievement condition involved a mathematical and a verbal challenge ; the rejection condition involved two social interaction challenges .  Self-reported affect and salivary cortisol were measured throughout each stress session ( baseline , stress , and poststress periods ) . RESULTS There were no sex differences in mood ratings following the stressors ; however , cortisol responses showed the predicted gender by condition by time interaction . Men showed significantly greater cortisol responses to the achievement challenges , but women showed greater cortisol responses to the social rejection challenges . CONCLUSIONS Women appear more physiologically reactive to social rejection challenges , but men react more to achievement challenges . Women 's greater reactivity to rejection stress may contribute to the increased rates of affective disorders in women The current cross-sectional study investigated basal and stress-challenged hypothalamic-pituitary-adrenocortical ( HPA ) system function in 102 five-year old kindergarten children ( 59 boys , 43 girls ) who had been assessed by a comprehensive psychological and behavioral test battery .  Baseline HPA system activity was significantly increased in girls when compared to boys ( p<0.001 ) . Furthermore , basal HPA system activity predicted a high hormonal release during stress with -- again -- girls showing higher hormonal responses than boys ( p<0.01 ) . Importantly , increased HPA system activity ( baseline and stress-challenged ) was significantly associated with hyperactivity/impulsivity and emotional problems in boys and with positive emotions in girls ( p<0.05 ) . These results suggest an occurrence of neurobiological alterations early in development . The observed neurobiological changes are gender specific already at the age of 5 years . Prospect i ve long-term follow up of the identified subjects with HPA axis alterations will clarify if these markers are predictive for the onset of psychiatric disorders Estrogens are reported to provide protection against the development of cardiovascular disease in women , but the mechanisms underlying these effects are not well defined . We hypothesized that estrogen might affect the hormonal responses to stress . We therefore studied cortisol , ACTH , epinephrine , norepinephrine , and norepinephrine spillover and hemodynamic responses to a 10-min mental arithmetic test in 12 perimenopausal women r and omized to 8 weeks of estrogen supplementation ( estradiol valerate , 2 mg daily ; n = 7 ) or placebo ( n = 5 ) . Total body and forearm norepinephrine spillover were measured by radiotracer methodology . After supplementation with estradiol , the increases in both systolic and diastolic blood pressure in response to mental stress were reduced , and cortisol , ACTH , plasma epinephrine and norepinephrine , and total body norepinephrine spillover responses to stress were significantly attenuated ( P < 0.05 in each case ) . Forearm norepinephrine spillover was unchanged by estrogen , and there was no change in any of the responses after placebo . We conclude that estrogen supplementation  in perimenopausal women attenuates blood pressure , glucocorticoid , and catecholamine responses to psychological stress The current study sought to examine whether children 's spontaneous use of the emotion regulation strategies suppression and re appraisal during a psychosocial stress task was related to their cortisol and alpha-amylase responses to that task . Salivary cortisol and alpha-amylase responses to a psychosocial stress task were assessed in 158 10-year-old children ( 83 girls ) . The children completed a self-report question naire measuring use of  re appraisal and suppression  during the task . Results showed overall increases in cortisol and alpha-amylase in response to the stressor , with higher cortisol reactivity in girls than in boys . With regard to emotion regulation , more use of suppression was related to lower cortisol reactivity in girls , and lower alpha-amylase reactivity and quicker alpha-amylase recovery in all children . The use of re appraisal  was not related to the children 's cortisol or alpha-amylase responses . The current study is the first to investigate the relation between the spontaneous use of re appraisal and suppression , and physiological stress responses to a psychosocial stressor in children . Our results indicate that re appraisal and suppression are used and can be measured even in 10-year-olds . At this age re appraisal appears ineffective at down-regulating physiological responses , while suppression was related to lower physiological responses . For cortisol reactivity there was a sex difference in the relation with suppression , indicating the importance of including sex as a moderator variable in research study ing stress reactivity and its correlates in this age group 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 , result ing 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 can not 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 Sex differences in rates of internalizing disorders have been attributed in part to heightened sensitivity to stress in females . While the sex difference in disorder rates becomes most pronounced in adolescence , developmental research suggests that stress reactivity in girls may be related to elevated internalizing symptoms even in childhood . We therefore examined whether child sex moderated associations between symptoms of psychopathology and cortisol reactivity to a st and ardized stress task in 409 three-year-old community-dwelling children .  Anxious symptoms were associated with elevated cortisol reactivity , but only in girls . Externalizing symptoms were unrelated to baseline cortisol or cortisol reactivity , and no evidence for moderation by child sex was found . Results suggest that cortisol reactivity to stress in early childhood has a sex-specific association with girls ' internalizing symptoms This study investigates basal levels of cortisol and dehydroepi and rosterone ( DHEA ) , and their relation to gender and pubertal development , in healthy children and adolescents .  Salivary cortisol and DHEA levels were examined in 129 normally developing subjects aged eight to 16 years . Subjects provided morning ( 08:00 h ) and evening ( 20:00 h ) saliva sample s over four consecutive days . Pubertal stage was assessed using Tanner stage sketches , and subjects were grouped according to their general status of pubertal development ( pre-early puberty : Tanner stageII ) . Results showed that morning salivary cortisol in mid-postpubertal girls was greater than in mid-postpubertal boys , but not pre-early pubertal girls and boys . Mean levels of salivary DHEA were greater in mid-postpubertal boys and girls than in pre-early pubertal boys and girls . Changes in hypothalamic-pituitary-adrenal ( HPA ) axis function that occur during puberty may have implication s for immediate and long-term adolescent health OBJECTIVE Our purpose was to determine the pattern of reactivity to stress in premenopausal and postmenopausal women and to assess the effects of estrogen . STUDY DESIGN A behavioral stress test was given to premenopausal ( n = 13 ) and postmenopausal women ( n = 36 ) . Biophysical and neuroendocrine responses were measured during and on completion of the stress test . The postmenopausal women were then r and omized to placebo or transdermal estradiol treatment for 6 weeks , at which time another behavioral stress test was given . RESULTS Stress reactivity to math and speech tasks elicited significantly greater systolic blood pressure responses in postmenopausal women compared with premenopausal women ( p < 0.05 ) . On retesting , significant biophysical responses that were present during the initial stress testing were still present ( p < 0.05 ) in the placebo group but were blunted with estrogen treatment . Plasma corticotropin , cortisol , and rostenedione , and norepinephrine increased during testing to a similar degree in premenopausal and postmenopausal women ; this response was maintained after placebo treatment . Postmenopausal women treated with estrogen had blunted responses . CONCLUSION Significant differences in responses to psychologic stress exist in premenopausal and postmenopausal women . The lack of adaptation may account in part for the increased risk of cardiovascular disease in postmenopausal women .  Estrogen appears to blunt the stress-induced response OBJECTIVE Consistent sex differences in regulation of the hypothalamic pituitary adrenocortical ( HPA ) axis have been shown in animal models and emerge over puberty . However , parallel work in humans is lacking despite implication s for elucidating the emergence of sex differences in depression over puberty . We investigated sex differences in HPA response to corticotropin releasing hormone ( CRH ) challenge over puberty in a carefully screened normative sample . METHODS Participants were 68 healthy children ( 41 % girls ) , ages 6 - 16 , with no personal or family history of psychiatric disorder . Pubertal maturation was determined by Tanner staging . Following 24h of adaptation , 9 - 10 plasma cortisol sample s were collected over 30 - 40 min pre-infusion baseline , 1 μg/kg CRH infusion , and 90 - 180 min post-infusion recovery . Thirty-seven participants completed 2 + CRH challenges allowing inclusion of cross-sectional and longitudinal data in all analyses . The influence of gender and pubertal maturation on parameters of cortis 
    Output:
    
Discussion Sex differences in HPA axis reactivity appear to be present in childhood , although evidence is not unequivocal .