Effect of age and sex on cortisol secretion in depressives and normals

Halbreich, Uriel; Asnis, Gregory M.; Zumoff, Barnett; Nathan, Rajan; Shindledecker, Richard

doi:10.1016/0165-1781(84)90037-4

Cited by 119 publications

(43 citation statements)

References 16 publications

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“…The rise in calculated ACTH efficacy with age in women is consistent with measurements of cortisol concentrations and production rates in several clinical studies (27,43,48,48,54). Conversely, the fall in ACTH efficacy with age in men is consistent with declining cortisol levels inferred in other investigations (2,16,24,40,43,49,55,61,63,64,78).…”

Section: Discussionsupporting

confidence: 72%

Sex defines the age dependence of endogenous ACTH-cortisol dose responsiveness

Keenan

Roelfsema

Carroll

et al. 2009

American Journal of Physiology-Regulatory, Integrative and Comp

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Whether similar sex differences operate in humans is unknown. To test this notion, we estimated ACTH-cortisol dose-response properties analytically in 48 healthy adults (n ϭ 22 women, n ϭ 26 men), ages 18 -77 yr, body mass index (BMI) 18 -32 kg/m 2 , previously studied at two medical centers. Plasma ACTH and cortisol concentrations were measured every 10 min for 24 h. The 145 sample pairs were used in each subject to estimate ACTH-cortisol drive via a logistic function. Statistical analyses revealed that 24-h cortisol secretion (Ͼ82% pulsatile) fell in men (r ϭ Ϫ0.38, P ϭ 0.028) and rose in women (r ϭ ϩ0.37, P ϭ 0.045) with age (P ϭ 0.01 sex effect). The mechanisms involved decreased ACTH efficacy with age in men (r ϭ Ϫ0.35, P ϭ 0.04), and increased ACTH efficacy with age in women (r ϭ ϩ0.42, P ϭ 0.025) [P ϭ 0.009 sex effect]. ACTH potency diminished with higher BMI in men (r ϭ ϩ0.38, P ϭ 0.029) and in the cohort as a whole (r ϭ 0.34, P ϭ 0.0085). These outcomes demonstrate that sex, age, and BMI modulate selective properties of endogenous ACTHcortisol drive in humans, thereby indicating the need to control these three major variables in experimental comparisons. adrenal; aging; sex; men; women; secretion IN EXPERIMENTAL ANIMALS, ESTROGENS sensitize and androgens mute corticotropic-axis responses to stress (15,21,60,75). Data in the human are indirect and controversial. For example, in one study in eight hypogonadal men, cortisol production rates were normal (77), whereas in another study, leuprolideinduced gonadoprivation unmasked greater ACTH and cortisol responses to corticotropin-releasing hormones (CRH) in young and middle-aged men than premenopausal women (59). Analyses of young hypogonadal adults further suggest that serotoninergic agonists and psychosocial stress stimulate greater corticotropic-adrenal responses in young men than young women (49, 61). On the other hand, cortisol concentrations are reportedly higher in women than men during early sleep, dexamethasone suppression, interleukin-6 infusion, growth hormone-releasing hormone (GHRH) injection, CRH stimulation, physostigmine administration, and psychosocial stress (8,43,48,64,78).In some investigations, age appears to augment ACTH and cortisol release in both sexes after selected stressors (8,26,30,43,48). Nonetheless, other studies have reported no age or sex effects (19,29,32,46,48,53). Certain of these discrepancies could be due to ethnicity differences (14, 80), time-of-day effects (72), measurement of cortisol in plasma, saliva, or urine (41, 43, 58), nature of stressor (54, 71), basal vs. stressed states (2, 81), concurrent obesity (1,23,33,67,68,70), estrogen use (46), stage of menstrual cycle (40), dietary carbohydrate intake (65), and potential sex-by-age interactions (78). The last consideration has been assessed in untreated children (28) and in adults following sequential dexamethasone/CRH exposure (30).To date, no clinical studies have appraised the individual and interactive effects of sex and age on adrenal responses to endogenous ...

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Section: Discussionsupporting

confidence: 72%

Sex defines the age dependence of endogenous ACTH-cortisol dose responsiveness

Keenan

Roelfsema

Carroll

et al. 2009

American Journal of Physiology-Regulatory, Integrative and Comp

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“…This result is in line with investigators who have found age to be positively associated with COR secretion during depression [33,34], especially in women [35] and severely depressed patients [36].…”

Section: Discussionsupporting

confidence: 82%

Influence of Mirtazapine on Salivary Cortisol in Depressed Patients

Laakmann¹,

Hennig

Baghai³

et al. 2003

Neuropsychobiology

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Unlike other antidepressants, mirtazapine does not inhibit the reuptake of norepinephrine or serotonin but acts as an antagonist at presynaptic α₂-receptors, at postsynaptic 5-HT2 and 5-HT3 receptors, and at histaminergic H1 receptors. Furthermore, mirtazapine has been shown to acutely inhibit cortisol secretion in healthy subjects. In the present study, the impact of mirtazapine treatment on salivary cortisol secretion was investigated in 12 patients (4 men, 8 women) suffering from major depression according to DSM-IV criteria. Patients were treated with mirtazapine for 3 weeks, receiving 15 mg mirtazapine on day 0, 30 mg on day 1 and 45 mg per day from day 2 up to the end of the study (day 21). Response to mirtazapine treatment was defined by a reduction of at least 50% in the Hamilton Rating Scale for Depression after 3 weeks of therapy. Salivary cortisol concentrations were measured before treatment (day –1), at the beginning of treatment (day 0), after 1 week (day 7) and after 3 weeks (day 21) of treatment with mirtazapine. Saliva samples were collected hourly from 08.00 until 20.00 h. The area under the curve values served as parameter for the salivary cortisol secretion. Following analysis of variance with a repeated measures design, tests with contrasts revealed a significant reduction of cortisol concentrations already after 1 day of mirtazapine treatment that was comparable in responders and nonresponders. In addition to new pharmacological approaches such as CRH1 receptor antagonists, mirtazapine therefore appears to be an effective strategy to decrease hypercortisolism and restore HPA system dysregulation in depression. However, the importance of the acute inhibitory effects of mirtazapine on cortisol secretion for its antidepressant efficacy has to be further clarified.

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“…Finally, we found no evidence of alterations in circadian or ultradian parameters of the HPA axis in depressed women. While surprising, the young age of the study population may account for the relatively normal HPA axis parameters, since age appears to be a significant factor in phase advancing the cortisol rhythm and also in increasing the rates of dexamethasone non-suppression Halbreich et al 1984;Oxenkrug et al 1983;Van Cauter et al 1996). Finally, the relatively small increases in cortisol observed in these depressed subjects may be enough to restrain the central overactivity, leading to a great underestimate of the degree of HPA axis activation and circadian disruption observed in these subjects.…”

Section: Discussionmentioning

confidence: 96%