Biomedical subjects

Holger Jahn

Publications and source records attributed to Holger Jahn.

At least 19 recordsLinked to original sources

PubMed2006

Effects of treatment with acamprosate on beta-endorphin plasma concentration in humans with high alcohol preference.

Treatment with acamprosate, a compound used for relapse prevention treatment of alcoholism, was recently shown to be associated with increased plasma concentration of beta-endorphin in rats selectively bred for high alcohol preference. The aim of our study was to prove this result in a comparative clinical study with a corresponding design. We studied 51 alcohol dependent patients following alcohol withdrawal during treatment with acamprosate versus placebo for 4 weeks. Data were analyzed for patients with high alcohol preference (HP) and low alcohol preference (LP) by dichotomizing the sample according to median alcohol intake prior to detoxification. In line with pre-clinical data, beta-endorphin plasma concentration in HP patients was significantly lower compared with LP patients. Four weeks of treatment with acamprosate resulted in a significantly increased beta-endorphin plasma concentration compared with placebo and a significant difference in HP patients but not in LP patients. In conclusion, acamprosate seems to modulate the endogenous opioid system. Our data are in accordance with the assumption that the effect of acamprosate on endorphin plasma concentrations is mainly based on the effect in the high preferring subgroup. Since beta-endorphin deficiency was earlier associated with alcohol craving and anxiety during withdrawal, abstinence maintaining effects of acamprosate might at least be partially related with the ability to modulate opioidergic activity especially in the subsample of HP patients with an attenuated opioidergic activity during this state.

Acamprosate↗

PubMed2006

Hypothalamic-pituitary-adrenocortical axis activity: a target of pharmacological anticraving treatment?

BACKGROUND: An association between the activity of the hypothalamic-pituitary-adrenocortical (HPA) axis and alcohol intake behavior is currently discussed. We examined the relationship between efficacy of pharmacological anticraving treatment and HPA axis activity in the relapse prevention treatment of alcoholism. METHODS: In 160 patients suffering from alcoholism, we measured plasma adrenocorticotropic hormone (ACTH) and cortisol during placebo-controlled relapse prevention treatment with naltrexone and/or acamprosate. RESULTS: In the placebo group, ACTH and cortisol decreased during early abstinence. Treatment with naltrexone and acamprosate prevented this course. Increased ACTH and cortisol during treatment was associated with a reduced risk of relapse. CONCLUSIONS: These findings suggest that heightened HPA responsiveness might contribute to relapse-preventing effects of anticraving compounds in alcoholism.

Acamprosate↗

PubMed2006

Megestrol attenuates the hormonal response to CCK-4-induced panic attacks.

Progestational hormones may have anxiolytic properties. CCK-4 (cholecystokinin tetrapeptide) can be used pharmacologically to induce panic attacks both in normal controls and patients suffering from panic disorder. In this study we compared the effects of pretreatment with the progestational hormone megestrol and placebo on CCK-4-induced panic attacks and stress hormone release in healthy male controls. Using a double-blind balanced design, we pretreated 10 medically and psychiatrically healthy male controls with placebo or megestrol 160 mg at 11 p.m. and 8 a.m. (sigma=320 mg) prior to the experiment. Following 1 h of rest, 12 blood samples were drawn between 1,000 h and 1,300 h and analyzed for ACTH and cortisol levels. At 1,100 h, subjects received an intravenous injection of 50 microg CCK-4. Clinical ratings were performed at 1,045 h and 1,110 h, and included the Acute Panic Inventory (API), International Diagnostic Checklist (IDCL), as well as a visual analog scale (VAS) for anxiety and tension. CCK-4 significantly increased anxiety and tension. Pretreatment with megestrol showed no significant effect on clinical ratings. Baseline ACTH and cortisol levels, as well as ACTH and cortisol levels after administration of CCK-4, were significantly reduced after pretreatment with megestrol. In a sample of healthy male controls, pretreatment with megestrol had a profound effect on the hypothalamic-pituitary-adrenal (HPA) axis, whereas the clinical effects on panic attacks were weak. Further studies in a larger sample of subjects, including both females and patients suffering from panic disorder, seem warranted.

Adrenocorticotropic Hormone↗

PubMed2006

Pharmacological treatment of non-Alzheimer dementias.

PURPOSE OF REVIEW: One hundred years after the first description by Alois Alzheimer and with the advent of first pharmacological treatments, most researchers concentrate on Alzheimer's disease. Millions of patients, however, suffer from other dementias and search for help beyond diagnosis. RECENT FINDINGS: New clinical data concerning the treatment of non-Alzheimer dementias mainly relate to the clinical use of antidementiva that is already approved for the treatment of Alzheimer's disease. Few studies test new pharmacological paradigmata. For some forms like vascular dementias, the possibility of prevention is the most valuable approach that should be enforced more aggressively. For other savaging dementias new unconventional treatment trials should be encouraged. SUMMARY: Research for non-Alzheimer dementias lags behind those for the Alzheimer field. For many patients, we still have nothing but words. At the same time, probably with regard to cost constraints, some acteurs like health insurances and legislators are inclined to nurture therapeutic nihilism and cultivate ethical qualms and demurs instead of supporting clinical trials or at least not blocking them with bureaucratic hand-cuffs, whereas pharmaceutical companies contemplate naturally over questions like return of investment. The clinical researchers should fight this fatigue and look for ways out of this quagmire for our patients.

Clinical Trials as Topic↗

PubMed2005

Increasing leptin precedes craving and relapse during pharmacological abstinence maintenance treatment of alcoholism.

The appetite regulating peptide leptin has recently been associated with craving for alcohol and lifetime ethanol intake. However, effects of anti-craving drugs on leptin have not been studied until now. The objective of our study was to test the hypothesis whether leptin plasma concentration in abstinent alcohol addicts during treatment with naltrexone vs. acamprosate is associated with abstinence duration and craving for alcohol. Leptin plasma concentration was measured in 160 recently detoxified alcohol addicts during a double-blind, placebo-controlled relapse prevention trial with naltrexone vs. acamprosate vs. naltrexone plus acamprosate. During placebo treatment, increasing leptin plasma concentration was observed, whereas during combined treatment with naltrexone and acamprosate, leptin decreased significantly. The change from baseline of leptin plasma levels after weeks 4, 8 and 12 was inversely correlated with duration of abstinence and, after 4 weeks, positively correlated with self-rated craving. In summary, the study presents first evidence for an association of increasing leptin plasma concentrations with relapse to renewed alcohol intake in detoxified alcoholics. Moreover, there are hints for an interaction between pharmacological anti-craving treatment, plasma concentration of leptin, and abstinence duration.

Acamprosate↗

PubMed2005

Pharmacological relapse prevention of alcoholism: clinical predictors of outcome.

OBJECTIVE: The efficacy of pharmacological relapse prevention in alcoholism with acamprosate and naltrexone has been supported by several controlled trials. It remains uncertain whether any differential indication for treatment exists. METHODS: We evaluated outcome data of a controlled trial on acamprosate and naltrexone in patients with low vs. high baseline somatic distress, depression and anxiety (Symptom Checklist-90, SCL-90), low vs. high baseline craving, and according to typological differentiation as proposed by Cloninger and Lesch. These variables have previously been suggested to be predictors of outcome. RESULTS: Comparing the course of abstinence rates, acamprosate was mainly efficacious in patients with low baseline somatic distress, whereas naltrexone was effective especially in patients with high baseline depression. Baseline craving showed no predictive value. Pharmacological treatment was efficacious in type II alcoholics according to Cloninger. Applying Lesch's typological differentiation, acamprosate was shown to be mainly effective in type I, whereas naltrexone revealed best treatment effects in type III and IV. CONCLUSION: The study supports the hypothesis that different subgroups of alcohol dependent subjects might benefit from a differential treatment with either naltrexone or acamprosate. Baseline psychopathology and especially typological differentiation might be useful in matching patients to distinct pharmacotherapeutic interventions. .

Acamprosate↗

PubMed2004

Dimensional structure of the Hamilton Depression Rating Scale in patients with obsessive-compulsive disorder.

Comorbid depression is frequent in obsessive-compulsive disorder (OCD) and is acknowledged as a major confound in biological and neurocognitive investigations in OCD. The aim of the present study was to assess the distribution of depressive symptoms in a large OCD sample (n=162) and to analyze the dimensional structure of the Hamilton Depression Rating Scale (HDRS) in OCD. Major depressive disorder according to DSM-IV criteria was apparent in approximately one third of the patients. Frequent symptoms were depressed mood, reduced ability to work, anxiety symptoms and guilt feelings. HDRS scores were submitted to a varimax-rotated factor analysis. In accordance with studies conducted with depressed samples, multi-dimensional solutions suggesting three to six factors emerged. Subsequent confirmatory factor analysis revealed satisfactory fit indices for a four-factorial solution comprising core depressive symptoms, sleep disturbance, anxiety and gastrointestinal problems. Aggression-related obsessions as well as the overall severity of obsessions were related to core depressive symptoms. Anxiety symptoms were associated with excessive rituals. Greater recognition of depressive sub-components may help to raise the replicability of empirical findings in OCD research as there is evidence from both depression and OCD samples that distinct depressive syndromes have different biological correlates.

Adult↗

PubMed2004

Metyrapone as additive treatment in major depression: a double-blind and placebo-controlled trial.

BACKGROUND: Inhibitors of steroid synthesis have been reported to exert antidepressive effects, according to preliminary findings. OBJECTIVE: To test whether the addition of metyrapone to standard antidepressants induces a more rapid, more efficacious, and sustained treatment response in patients with major depression. DESIGN: Double-blind, randomized, placebo-controlled trial. SETTING: Hospitalized care. PATIENTS: Sixty-three inpatients with a DSM-IV diagnosis of major depression and a baseline score 18 points or higher on the Hamilton Rating Scale for Depression. INTERVENTIONS: Random allocation to 2 treatment groups receiving either placebo or metyrapone (1 g/d) for the first 3 weeks during a 5-week treatment with standard serotonergic antidepressants (nefazodone or fluvoxamine). MAIN OUTCOME MEASURES: Primary outcome criteria were the number of responders and the time to onset of action. Responder rates were considered twice after 3 and 5 weeks with a definition of treatment response as 30% and 50% reduction, respectively, of baseline Hamilton Rating Scale for Depression scores. Onset of action was defined as the time point at which at least a 20% reduction of baseline Hamilton Rating Scale for Depression scores occurred. RESULTS: Using intention-to-treat analysis, we found that a higher proportion of patients receiving metyrapone showed a positive treatment response at day 21 (23 of 33 patients) and at day 35 (19 of 33 patients) compared with placebo patients (day 21: 13 of 30 patients; Fisher exact P = .031; day 35: 10 of 30 patients; Fisher exact P = .047). The clinical course of patients treated with metyrapone showed an earlier onset of action (Kaplan-Meier analysis; log-rank test P<.006) beginning in the first week. The plasma concentrations of corticotropin and deoxycortisol were significantly higher during metyrapone treatment (multivariate analysis of covariance, P<.05), whereas cortisol remained largely unchanged. Metyrapone treatment was well tolerated without serious adverse effects. CONCLUSIONS: Metyrapone is an effective adjunct in the treatment of major depression, accelerating the onset of antidepressant action. A better treatment outcome compared with standard treatment and a sustained antidepressive effect were observed.

Adrenocorticotropic Hormone↗

PubMed2004

Overnight metyrapone and combined dexamethasone/metyrapone tests in post-traumatic stress disorder: preliminary findings.

Using overnight metyrapone and combined dexamethasone/metyrapone tests, hypothalamic-pituitary-adrenocortical (HPA) axis feedback regulation was characterised in 10 patients with post-traumatic stress disorder (PTSD) and 10 matched healthy comparison subjects. Significant treatment effects of both metyrapone and the combination of dexamethasone and metyrapone were observed for adrenocorticotropic hormone (ACTH), 11-deoxycortisol (11-DOC) and cortisol, but no differences between patients and comparison subjects emerged. Dose-response studies using metyrapone and glucocorticoid agonists are needed to further investigate HPA axis regulation in PTSD.

Adrenocorticotropic Hormone↗

PubMed2004

Adjunctive use of reboxetine in schizophrenia.

BACKGROUND: Schizophrenia is frequently complicated by depressive or negative symptoms that respond only moderately to treatment with antipsychotic drugs. Reboxetine is a novel antidepressant, which inhibits the reuptake of norepinephrine. We sought to study the efficacy and tolerability of the adjunctive use of reboxetine in a cohort of schizophrenic patients with prominent depressive or negative symptoms. METHODS: Sixteen schizophrenic inpatients were recruited for this study. All subjects received 4-8 mg of reboxetine/day while the antipsychotic medication (typical antipsychotics = 4; atypical antipsychotics = 12) was continued. All subjects underwent a standardized assessment including PANSS, CGI, HAMD, and CDSS before and after treatment with reboxetine (mean 26 +/- 17 d). RESULTS: All subjects tolerated treatment with reboxetine. Adverse effects were mild and did not require discontinuation of reboxetine. All clinical scores (PANSS 93.1 vs. 63.1; CGI 5.4 vs. 4.1; HAMD 20.4 vs. 8.1; CDSS 12.5 vs. 4.6) improved significantly under adjunctive treatment with reboxetine (all P < 0.01). CONCLUSION: The adjunctive use of reboxetine in schizophrenic patients was safe and well-tolerated. Our results suggest that the adjunctive use of reboxetine may be an effective treatment for depressive and negative symptoms in schizophrenia.

Adult↗

PubMed2003

Sleep endocrine effects of the 11-beta-hydroxysteroiddehydrogenase inhibitor metyrapone.

STUDY OBJECTIVES: Besides regulating hormone secretion, steroids also modulate sleep architecture in specific ways. To simulate a state of altered glucocorticoid- and mineralocorticoid-receptor occupation, we administered metyrapone, an 11-beta-hydroxylase inhibitor, that blocks adrenal cortisol synthesis and inhibits the 11-beta-hydroxysteroiddehydrogenase type-1 enzyme in the central nervous system and investigated endocrine changes and the sleep electroencephalogram. DESIGN: Each volunteer spent 4 nights in the sleep laboratory, the first of which served to habituate the subject to the conditions in the laboratory. The volunteers underwent 3 trial conditions in random order and in a single-blind design receiving 2 doses of metyrapone (4.5 g or 6.0 g) or placebo on the day before the sleep electroencephalogram recordings. SETTING: Sleep laboratory. PARTICIPANTS: 8 healthy male volunteers. MEASUREMENTS AND RESULTS: The corticotropin secretion was significantly enhanced by metyrapone, while the cortisol secretion remained largely unchanged. Growth hormone, progesterone, and dehydroepiandrosterone concentrations were also significantly increased by both doses. Metyrapone induced a pronounced reduction in slow-wave sleep and had slight but nonlinear effects upon rapid eye movement sleep. Parameters of sleep quality were not different between groups. CONCLUSIONS: Metyrapone induces pronounced effects on hormonal secretion and the sleep electroencephalogram. These results are in part comparable to those from experiments with the administration of corticotropin-releasing hormone and with experiments that deplete mineralocorticoid receptors. The findings may be explained by altered steroid synthesis proximal to the enzyme block. Metyrapone exerts not only effects upon adrenocortical steroid synthesis, but also important extra-adrenal effects on central corticosteroid metabolism.

11-beta-Hydroxysteroid Dehydrogenases↗

PubMed2003

Acute effects of megestrol on the hypothalamic-pituitary-adrenal axis.

BACKGROUND: Clinical observations suggest that prolonged treatment with megestrol can lead to Cushing-like symptoms, while withdrawal of prolonged treatment with megestrol may result in adrenal insufficiency. However, only little is known about the acute effects of megestrol on the hypothalamic-pituitary-adrenal (HPA) axis. As part of an endocrine study, we evaluated the acute effects of megestrol, hydrocortisone and placebo on morning cortisol and ACTH levels. METHOD: . Using a balanced double-blind design, ten healthy male subjects were treated at 11:00 p.m. and 8:00 a.m. with megestrol (total dose 320 mg), hydrocortisone (total dose 30 mg) or placebo. After 1 h of rest, blood was drawn at 10:00 a.m. and 10:30 a.m. for determination of cortisol and ACTH levels. RESULTS: . Compared to placebo, acute administration of megestrol resulted in a significant decrease in morning ACTH and cortisol levels. The suppression of ACTH after pretreatment with megestrol was less pronounced than after pretreatment with hydrocortisone. CONCLUSIONS: Our results suggest that megestrol exerts glucocorticoid-like effects and has an acute depressing effect on the HPA axis. Therefore alterations in the steroid system should be included in the differential diagnosis of all subjects under treatment with megestrol.

Adrenocorticotropic Hormone↗

PubMed2003

The mineralocorticoid receptor agonist, fludrocortisone, inhibits pituitary-adrenal activity in humans after pre-treatment with metyrapone.

Whereas animal studies have shown a clear inhibitory effect of hippocampal mineralocorticoid receptors (MR) on hypothalamic-pituitary-adrenal (HPA) axis activity, investigations in humans revealed equivocal results. To further clarify the influence of MR in HPA activity we studied 10 healthy men during the circadian nadir of HPA activity (14:00 to 21:00) after pre-treatment with 3 g metyrapone to minimize the impact of basal endogenous cortisol secretion. On three separate occasions, in a placebo-controlled design, subjects received in a randomized order either 0.5 mg fludrocortisone p.o. or 0.2 mg aldosterone i.v. or placebo. Fludrocortisone exerted a significant inhibition of ACTH, cortisol and 11-desoxycortisol (p < 0.05), whereas no such effect was observed after aldosterone or placebo. These preliminary data suggest that MR are involved in the inhibition of the HPA axis during the circadian nadir of glucocorticoid concentrations in humans.

Adrenocorticotropic Hormone↗

PubMed2003

Involvement of NMDA receptors in alcohol-mediated behavior: mice with reduced affinity of the NMDA R1 glycine binding site display an attenuated sensitivity to ethanol.

BACKGROUND: Ethanol antagonizes central effects of glutamate by inhibition of the N-methyl-D-aspartate (NMDA) receptor function. The co-agonist glycine has been shown to reverse alcohol-mediated effects. The aim of this study was to evaluate the influence of the glycine binding site of the NMDA receptor on the behavioral effects of alcohol by investigating mice with an 80% reduced affinity of the NMDA R1 subunit for glycine (Grin1(D481N)). METHODS: Free-choice and forced alcohol intake was studied over a period of 52 days. Anxiolytic activity (elevated plus maze, open field) and motor coordination (rotarod) was tested after 3 days of forced alcohol intake and during ethanol withdrawal. RESULTS: In contrast to wild-type mice, alcohol-associated anxiolysis and motor impairment was attenuated in Grin1(D481N) mice during intoxication. Free-choice alcohol intake did not differ between wild-type and Grin1(D481N) mice. CONCLUSIONS: Our results give first evidence in vivo for a possible role of an altered NMDA-receptor complex with a hyposensitive glycine binding site for behavioral effects mediated by ethanol.

Alcohol Drinking↗

PubMed2003

Comparing and combining naltrexone and acamprosate in relapse prevention of alcoholism: a double-blind, placebo-controlled study.

BACKGROUND: Naltrexone and acamprosate have been shown to be effective in relapse prevention of alcoholism via different pharmacologic mechanisms. Since it remains uncertain whether both substances are equally efficient and whether a combination of both drugs potentiates the efficacy, we conducted the first published controlled study comparing and combining both compounds. METHODS: After detoxification, 160 patients with alcoholism participated in a randomized, double-blind, placebo-controlled protocol. Patients received naltrexone, acamprosate, naltrexone plus acamprosate, or placebo for 12 weeks. Patients were assessed weekly by interview, self-report, questionnaires, and laboratory screening. Time to first drink, time to relapse, and the cumulative abstinence time were the primary outcome measures. RESULTS: Naltrexone, acamprosate, and the combined medication were significantly more effective than placebo. Comparing the course of nonrelapse rates between naltrexone and acamprosate, the naltrexone group showed a tendency for a better outcome regarding time to first drink and time to relapse. The combined medication was most effective with significantly lower relapse rates than placebo and acamprosate but not naltrexone. CONCLUSIONS: The results of this study support the efficacy of pharmacotherapeutic strategies in the relapse prevention of alcoholism. Naltrexone and acamprosate, especially in combination, considerably enhance the potential of relapse prevention.

Acamprosate↗

PubMed2003

Modulation of sympathetic activity by corticotropin-releasing hormone and atrial natriuretic peptide.

BACKGROUND: Heart rate variability represents a reliable marker to delineate the status of autonomic nervous system (ANS) function and alterations due to stress in vivo. Interestingly, up to now the effects of corticotropin-releasing hormone (CRH), a key regulator of the stress hormone system, upon heart rate variability are not sufficiently described. Hence, we attempted to investigate the ANS-effects of a CRH bolus and the modulatory influences of atrial natriuretic peptide (ANP), one of the most important functional antagonist of CRH actions. METHODS: 12 healthy male volunteers were administered 100 microg CRH as bolus injection at 15:00. Six randomly chosen subjects received 150 microg ANP dissolved in normal saline and six subjects a normal saline infusion from 14:45 to 15:15. From 13:00 to 17:00 an ECG was recorded and mean heart rate (HR), total power (TP), very low frequency (VLF), low frequency (LF), LF in normalized units (LF [nu]), high frequency (HF) domains and the LF/HF-ratio in the interval from 14:00 to 16:00 were determined. RESULTS: After administration of CRH a significant increase in HR and a fast reduction of TP were observed, which lasted about 1 h. Based upon spectral domain analyses the sympathetic activity after CRH administration as indicated by LF [nu] increased by 31% (mean location) during saline. Applying ANP this increase was reduced to 19% (mean location). The VLF component, which is considered to be based in part also on sympathetic influences, indicates comparable effect. During saline the VLF after CRH bolus remained largely unchanged, but was reduced to 66% by ANP. Though the vagal activity indicated by the HF component was reduced after CRH, no significant differences emerged between both treatments. The changes of the LF/HF-ratio were pronounced in both groups. During saline this ratio increased by about 111%, during ANP only by 43% (mean location). CONCLUSIONS: Based upon HRV analysis the CRH administration induced sympathotonic effects which were antagonized by ANP. The observed vagal changes were less pronounced and need further investigation. Further studies of autonomic effects by alterations of CRH secretion in depression and anxiety disorder are strongly warranted.

Adult↗

PubMed2003

Impact of comorbid depressive symptoms on nonverbal memory and visuospatial performance in obsessive-compulsive disorder.

INTRODUCTION: Recent research has suggested that some executive dysfunctions in obsessive-compulsive disorder (OCD) represent an epiphenomenon of comorbid depressive symptoms. The present study investigated whether the impact of comorbid depressive symptoms on cognitive dysfunction in OCD extends to nonverbal memory impairment. METHODS: A total of 32 OCD patients and 20 healthy controls took part in the study. Participants were administered a neurocognitive battery with a focus on nonverbal memory and visuospatial functions. RESULTS: While evidence was provided that neurocognitive processes necessitating visuospatial transformation and visuoconstruction are deficient in OCD patients regardless of comorbid depressive symptoms, nonverbal memory dysfunctions were only apparent for patients with elevated scores in the Hamilton Depression (HDRS) Rating Scale (total score > or = 8). Correlations with subscores of the HDRS revealed that core depressive symptoms are related to nonverbal memory deficits in OCD. Mental rotation, middle discrimination, and position discrimination were found to be unaffected in OCD. Y-BOCS scores, length of illness, onset of illness, number of hospital admissions, and checking compulsions were not associated with neurocognitive disturbances. CONCLUSIONS: Nonverbal memory is disturbed in only a subgroup of OCD patients displaying elevated HDRS scores (HDRS > or = 8). It is claimed but awaits further empirical testing that differences in depression profile across OCD studies have contributed to inconsistencies in prior investigations on neurocognitive functioning in OCD. Our results are questioning the hypothesis that nonverbal deficits are a causal factor for the development of checking compulsions.

Journal Article↗

PubMed2003

Mineralocorticoid receptor-mediated inhibition of the hypothalamic-pituitary-adrenal axis in aged humans.

In aged humans, diminished mineralocorticoid receptor (MR)-mediated feedback in the brain could contribute to impaired feedback regulation of the hypothalamic-pituitary-adrenal (HPA) axis, but no study specifically compared young and old individuals with regard to MR function. We examined 10 healthy young (mean age +/- SD [standard deviation] 26.1 +/- 2.9 years) and 10 elderly men (68.3 +/- 4.7 years) at the nadir of cortisol levels (2:00 pm-9:00 pm) when HPA activity is mainly controlled by the MR. After pretreatment with 3 g metyrapone to minimize the impact of basal endogenous cortisol secretion, participants received orally, in randomized order on two separate occasions, either 0.5 mg of the MR agonist fludrocortisone or placebo. Fludrocortisone significantly decreased maximum adrenocorticotropic hormone (ACTH) and cortisol concentrations in both groups. ACTH and cortisol values after fludrocortisone were significantly higher in older men compared with young men. Our results implicate that a decrease in MR-mediated negative feedback contributes to the diminished feedback activity in older humans.

Adrenocorticotropic Hormone↗