Plasma dehydroepiandrosterone and dehydroepiandrosterone sulfate in patients undergoing diagnostic coronary angiography

Serum levels of DHEA sulfate are inversely associated with cardiovascular death in men, and urinary dehydroepiandrosterone (DHEA) levels are inversely associated with clinical manifestations of coronary artery disease. These observations may be related to the antiproliferative effects of DHEA, resulting in inhibition of atherosclerotic intimal hyperplasia. To examine the relation between these steroids and a direct measure of coronary atherosclerosis, plasma DHEA and DHEA sulfate levels were determined in 206 middle-aged patients (103 men, 103 women) undergoing elective coronary angiography. Plasma DHEA sulfate levels were lower in men with at least one stenosis greater than or equal to 50% compared with those without any stenosis greater than or equal to 50% (4.9 +/- 2.7 versus 6.1 +/- 3.5 nmol/ml, p = 0.05). Levels of DHEA sulfate were also inversely related to the number of diseased coronary vessels (r = -0.20, p = 0.05) and a continuous measure of the extent of coronary atherosclerosis (r = -0.25, p = 0.01) in men. The association between DHEA sulfate levels and extent of coronary artery disease was independent of age and other conventional risk factors for coronary disease. In women, there was no association between plasma DHEA or DHEA sulfate levels and coronary disease. These data demonstrate a consistent, independent, inverse, dose-response relation between plasma DHEA sulfate levels and angiographically defined coronary atherosclerosis in men. Plasma DHEA sulfate may be another important and potentially modifiable risk factor for the development and progression of coronary atherosclerosis.     

A study on dehydroepiandrosterone sulfate in patients with essential hypertension

Alterations in the concentration of plasma dehydroepiandrosterone sulfate (DHEA-S) and cortisol in patients with essential hypertension (EH) were investigated. The subjects were 25 patients with EH: 7 of low plasma renin activity (PRA) group, 10 of normal PRA group and 8 of high PRA group; 7 normal subjects were used as the controls. Plasma DHEA-S and cortisol were measured before and after the following tests: (1) circadian rhythm (6:00, 16:00 and 24:00), (2) furosemide (0.7 mg/kg) test, (3) ACTH (12.5 IU/4 hr) infusion test, (4) dexamethasone (1.0 mg) test, (5) furosemide (0.7 mg/kg) test under dexamethasone (1.0 mg) treatment, (6) metopirone (1.5 g) test, (7) angiotensin II (8 ng/kg/min, 30 min) infusion test and (8) saline (1000 ml/hr) test. The alterations of the endogenous ACTH-adrenal hormone system as well as the renin-angiotensin-aldosterone system induced by these tests did not cause significant changes of plasma levels of DHEA-S in the 3 groups with EH. However, significant enhancement of plasma DHEA-S was observed after both the administration of exogenous ACTH and angiotensin II. It is considered that the responsiveness of DHEA-S to ACTH may increase in the low and normal PRA groups and that the responsiveness of DHEA-S to angiotensin II may increase in the high PRA group. Based on these results, it is suggested that plasma DHEA-S hardly or only partially participates as a causal factor of EH.     

Cerebrospinal fluid dehydroepiandrosterone levels are correlated with brain dehydroepiandrosterone levels, elevated in Alzheimer's disease, and related to neuropathological disease stage

OBJECTIVE: It is currently unknown whether cerebrospinal fluid (CSF) neurosteroid levels are related to brain neurosteroid levels in humans. CSF and brain dehydroepiandrosterone (DHEA) levels are elevated in patients with Alzheimer's disease (AD), but it is unclear whether CSF DHEA levels are correlated with brain DHEA levels within the same subject cohort. We therefore determined DHEA and pregnenolone levels in AD patients (n = 25) and cognitively intact control subjects (n = 16) in both CSF and temporal cortex. DESIGN: DHEA and pregnenolone levels were determined by gas chromatography/mass spectrometry preceded by HPLC. Frozen CSF and temporal cortex specimens were provided by the Alzheimer's Disease Research Center at Duke University Medical Center. Data were analyzed by Mann-Whitney U test statistic and Spearman correlational analyses. RESULTS: CSF DHEA levels are positively correlated with temporal cortex DHEA levels (r = 0.59, P < 0.0001) and neuropathological disease stage (Braak and Braak) (r = 0.42, P = 0.007). CSF pregnenolone levels are also positively correlated with temporal cortex pregnenolone levels (r = 0.57, P < 0.0001) and tend to be correlated with neuropathological disease stage (Braak) (r = 0.30, P = 0.06). CSF DHEA levels are elevated (P = 0.032), and pregnenolone levels tend to be elevated (P = 0.10) in patients with AD, compared with cognitively intact control subjects. CONCLUSIONS: These findings indicate that CSF DHEA and pregnenolone levels are correlated with temporal cortex brain levels of these neurosteroids and that CSF DHEA is elevated in AD and related to neuropathological disease stage. Neurosteroids may thus be relevant to the pathophysiology of AD.     

Adrenocorticotropic hormone and dehydroepiandrosterone sulfate levels of rheumatoid arthritis patients treated with glucocorticoids

To assess adrenal function with respect to the presence or absence of steroid therapy, we investigated differences in the blood levels of adrenocorticotropic hormone (ACTH) and dehydroepiandrosterone sulfate (DHEAS) in relation to steroid (prednisolone) administration in 123 patients with rheumatoid arthritis (RA). Levels of ACTH and DHEAS were significantly lower in the steroid-treated group than in the non-treated group (ACTH: 11.79 pg/ml vs 27.92 pg/ml) (DHEAS: 418.12 ng/ml vs 883.91 ng/ml) (P < 0.0001). We observed no steroid dose-related differences in ACTH levels. However, DHEAS levels showed a slight decrease at a prednisolone dose of 2.5 mg/day, with a significant decrease being observed at a dose of 5 mg/day when statistical adjustments were made for age and sex (P < 0.0001). At doses of 7.5 mg/day or greater, DHEAS levels were significantly lower than those for 5 mg/day (P < 0.0006). These results suggest that low-dose prednisolone reduces adrenal function in patients with RA. We recommend that doses of prednisolone should be limited to 5 mg/day or less in consideration of adrenal function when treating RA patients. The measurement of ACTH and DHEAS may be useful for evaluating adrenal function in patients with RA.     

Effects of dehydroepiandrosterone (DHEA) supplementation on hormonal, metabolic and behavioral status in patients with hypoadrenalism

Oral DHEA administration to patients with hypoadrenalism, in addition to glucocorticoid and mineralcorticoid replacement, may improve both well-being and hormonal/metabolic parameters. Twenty patients (13 men, 7 women, 26-76 yr, 11 with Addison's disease, 9 with central hypoadrenalism) were recruited in a placebo-controlled, randomized study. Hormone levels, carbohydrate and lipid parameters, bone metabolism, body composition and psychological parameters were evaluated at baseline and after treatment with DHEA 50 mg/day or placebo for 4 months. After 4 months of DHEA administration, serum DHEAS levels raised both in men (from 0.71+/-0.18 to 8.28+/-1.66 micropmol/l, p<0.005) and in women (from 0.25+/-0.07 to 5.65+/-1.93 micromol/l, p<0.05). Only in hypoadrenal women an increase in testosterone (T; from 0.4+/-0.1 to 1.45+/-0.26 nmol/l, p<0.05) and androstenedione (A; from 0.86+/-0.34 to 2.05+/-0.29 nmol/l, p<0.05) levels was observed. In men no significant modifications in T and 17-hydroxyprogesterone (17-OHP) levels were found, whereas serum SHBG significantly decreased. As far as the metabolic parameters are concerned, only in patients with Addison's disease a significant decrease in total cholesterol and in low-density lipoproteins after 4 months of DHEA administration was found. No changes in glucose metabolism and insulin sensitivity were observed. In basal conditions, mean serum osteocalcin (OC) was normal and significantly decreased after DHEA treatment. A significant reduction in body fat mass percentage (BF%) after DHEA administration was observed. As far as well-being is concerned, DHEA replacement did not cause any relevant variation of subjective health scales and sexuality in both sexes. Our study confirms that DHEA may be beneficial for female patients with hypoadrenalism, mainly in restoring androgen levels. Concerning the health status, more sensitive and specific instruments to measure the effects of DHEA treatment could be necessary.     

Adrenocorticotropic hormone and dehydroepiandrosterone sulfate levels of rheumatoid arthritis patients treated with glucocorticoids

Abstract

To assess adrenal function with respect to the presence or absence of steroid therapy, we investigated differences in the blood levels of adrenocorticotropic hormone (ACTH) and dehydroepiandrosterone sulfate (DHEAS) in relation to steroid (prednisolone) administration in 123 patients with rheumatoid arthritis (RA). Levels of ACTH and DHEAS were significantly lower in the steroid-treated group than in the non-treated group (ACTH: 11.79?pg/ml vs 27.92?pg/ml) (DHEAS: 418.12?ng/ml vs 883.91?ng/ml) (P < 0.0001). We observed no steroid dose-related differences in ACTH levels. However, DHEAS levels showed a slight decrease at a prednisolone dose of 2.5?mg/day, with a significant decrease being observed at a dose of 5?mg/day when statistical adjustments were made for age and sex (P < 0.0001). At doses of 7.5?mg/day or greater, DHEAS levels were significantly lower than those for 5?mg/day (P < 0.0006). These results suggest that low-dose prednisolone reduces adrenal function in patients with RA. We recommend that doses of prednisolone should be limited to 5?mg/day or less in consideration of adrenal function when treating RA patients. The measurement of ACTH and DHEAS may be useful for evaluating adrenal function in patients with RA.     

Interrelations of serum leptin levels with adrenocorticotropic hormone,basal cortisol and dehydroepiandrosterone sulphate levels in patients with metabolic syndrome

ObjectivesThe aim of this study was to determine serum leptin levels, adrenocorticotropic hormone, basal cortisol and dehydroepiandrosterone sulphate levels in patients with metabolic syndrome.Material and methodsThe study was comprised of 35 female patients and who applied to Eskisehir Osmangazi University Medicine Faculty Endocrinology polyclinic due to the symptoms of obesity and diagnosed as having metabolic syndrome.ResultsPlasma adrenocorticotropic hormone and dehydroepiandrosterone sulphate levels of metabolic syndrome group were lower than controls (P < 0.001, P < 0.05, respectively). Serum basal cortisol, resistin and leptin levels of metabolic syndrome group were higher than control (P < 005, P < 0.01, P < 0.001, respectively).ConclusionsOur data suggest that hormonal changes in metabolic syndrome pathogenesis may be related with increased leptin levels and for that reason leptin may be an important marker in metabolic syndrome.     

Double-blind placebo-controlled trial of oral dehydroepiandrosterone in patients with advanced HIV disease

OBJECTIVE: Plasma levels of dehydroepiandrosterone sulphate (DHEA-S) decrease with the progression of HIV disease. Here, we report on the efficacy and safety of the oral administration of DHEA as replacement therapy, in patients with advanced HIV disease, in a trial that was primarily aimed at assessing quality of life. DESIGN: The trial was randomized and double-blind. Thirty-two patients were allocated to either DHEA 50 mg per day for 4 months (n = 14) or a matching placebo (n = 18). Clinical data, virological and immunological surrogate markers of HIV infection, plasma levels of DHEA-S and the Medical Outcomes Study HIV Health Survey (MOS-HIV) quality of life scale were recorded every month. RESULTS: The mean age of the patients was 40 +/- 11 years. The mean CD4 cell count at baseline was 32.5 +/- 32.4 x 10(6)/l. The mean DHEA-S plasma level at baseline was 5.23 +/- 0.76 micromol/l. No side-effects related to DHEA occurred during the study. A statistically significant increase in the levels of DHEA-S was observed in the treated group throughout the study (P < 0.01). A significant improvement in the Mental Health and Health Distress dimension of MOS-HIV was observed in the DHEA treated group; P = 0.001 and 0.004, respectively. No change in CD4 cell counts was seen during follow-up. CONCLUSIONS: The administration of DHEA in patients with advanced HIV infection results in improved mental function scores as assessed by the MOS-HIV quality of life scale.     

Serum concentrations of dehydroepiandrosterone sulfate and leptin in obese patients with normal serum cholesterol

Normal (< 200 mg/dL) serum concentrations of cholesterol and a favorable ratio of cholesterol/high-density lipoprotein (HDL)-cholesterol are frequently seen in morbidly obese (body mass index [BMI] > 35 kg/m2) patients. Because it is unknown whether this subgroup is characterized by differences in other potential markers of cardiovascular disease, serum concentrations of dehydroepiandrosterone sulfate (DHEAS) and leptin were determined in 155 obese patients (BMI > 35 kg/m2, aged 20 to 50 years) with normal (n = 72) or with elevated (n = 83) total serum cholesterol. We found that seemingly negative marginal correlations between serum concentrations of DHEAS and cholesterol, as well as between DHEAS and the ratio cholesterol/HDL-cholesterol, were not any more apparent after correction for age, sex, and BMI. A negative correlation between serum leptin concentrations and the ratio cholesterol/HDL-cholesterol persisted after correction for age, sex, and BMI. In morbid obesity, there appears to be an association between serum concentrations of leptin and a more favorable lipid profile, whereas there is no direct interrelation between serum concentrations of cholesterol and DHEAS.     

High prolactin and low dehydroepiandrosterone sulphate serum levels in patients with severe systemic sclerosis

The aim was to determine serum levels of prolactin (PRL) and dehydroepiandrosterone sulphate (DHEAS), and to demonstrate a link between PRL or DHEAS and soluble immune mediators in patients with systemic sclerosis (SSc) with different degrees of disease-induced organ involvement. Thirty-one patients with SSc were studied to evaluate 18 possible disease manifestations. In the serum, PRL, DHEAS and soluble immune mediators were determined by ELISA. Compared to SSc with <9 disease manifestations, patients with > or =9 disease manifestations had higher PRL (P = 0.044), higher soluble interleukin 2 receptor (sIL-2R, P = 0.004) and vascular cell adhesion molecule (sVCAM, P = 0.044), and lower DHEAS (P = 0.029). PRL (R(Rank) = 0.490, P = 0.003) and DHEAS (R(Rank) = -0.399, P = 0.013) were significantly correlated with the number of disease manifestations. The inverse correlation between PRL and DHEAS showed a trend (P = 0.059). PRL correlated with sIL-2R (R(Rank) = 0.553, P = 0.001) and sVCAM (R(Rank) = 0.520, P = 0.002). The number of disease manifestations and sIL-2R correlated significantly (R(Rank) = 0.463, P = 0.006). Psychometric variables to examine the presence of depression were not measured, but from the general aspect, the patients were not suffering from major depression which may have influenced our results. In conclusion, this study demonstrates the close association between DHEAS and, particularly, PRL and SSc severity and T-lymphocyte mechanisms.      

Effect of dehydroepiandrosterone supplementation on fatty acid and hormone levels in patients with X-linked adrenoleucodystrophy

OBJECTIVE: In X-linked adrenoleucodystrophy (X-ALD) the peroxisomal beta-oxidation of saturated very long-chain fatty acids (VLCFAs; carbon length > 22 atoms) is impaired. These fatty acids accumulate in blood and tissues, in particular in the nervous system, adrenal cortex and testis. Most patients have a primary adrenocortical insufficiency with low levels of cortisol and dehydroepiandrosterone (DHEA) and its sulphate ester (DHEA-S), collectively called DHEA(S). Surprisingly, very low plasma levels of DHEA(S) may be found when plasma cortisol and ACTH levels are normal. In animal studies DHEA administration had a peroxisome proliferating effect and induced the expression of peroxisomal enzymes involved in the beta-oxidation of fatty acids. PATIENTS AND DESIGN: To study the effect of DHEA on fatty acids in X-ALD patients, we conducted a randomized double-blind study in which 14 men (age range 21-63 years) and one boy (12 years) received 50 mg of DHEA or placebo for 3 months, followed by a 1-month wash-out period, then 3 months of placebo or vice versa. RESULTS: A significant rise was seen in the plasma levels of DHEA-S, Delta4-androstenedione and IGF-I. The elevated saturated VLCFAs in plasma and erythrocytes did not change. However, in erythrocytes significant decreases were found in the total amount of fatty acids, in C16:0, C18:0 and in C20:4omega-6, C22:5omega-6, C18:1omega-9, C20:1omega-9 and C20:3omega-9. In plasma, decreases were found for C18:1omega-9 and increases for C20:1omega-9. CONCLUSIONS: Dehydroepiandrosterone supplementation for 3 months did not lower the elevated plasma levels of saturated very long-chain fatty acids in patients with X-linked adrenoleucodystrophy. Instead, a decrease in saturated and mono- and polyunsaturated fatty acids in erythrocytes and plasma was found. An increase of C20:1omega-9 was found in plasma only.     

Dissociation of serum dehydroepiandrosterone and dehydroepiandrosterone sulfate in septic shock

CONTEXT: Dehydroepiandrosterone (DHEA) replacement in sepsis has been advocated because of the sepsis-associated decrease in serum DHEA sulfate (DHEAS). However, experimental sepsis in rodents leads to down-regulation of DHEA sulfotransferase, which inactivates DHEA to DHEAS, theoretically resulting in higher DHEA levels. OBJECTIVE: The objective of the study was to test whether serum DHEA and DHEAS are dissociated in septic shock and to determine their association with circulating cortisol in the context of severity of disease and mortality. DESIGN, SETTING, AND PARTICIPANTS: This was a cross-sectional study consisting of 181 patients with septic shock, 31 patients with acute trauma, and 60 healthy controls. MAIN OUTCOME MEASURES: Serum cortisol, DHEA, and DHEAS were measured before and 60 min after ACTH stimulation. RESULTS: Serum cortisol was increased and DHEAS was decreased in both septic shock and trauma patients (all P < 0.001). However, compared with healthy controls, DHEA was significantly increased in sepsis but decreased after trauma (all P < 0.001). In sepsis, neither cortisol nor DHEA increased significantly after ACTH. Most severely ill patients had higher cortisol (P = 0.069) and lower DHEA (P = 0.076) and a significantly higher cortisol to DHEA ratio (P = 0.004). Similarly, the cortisol to DHEA ratio was significantly increased in nonsurvivors of septic shock (P = 0.026), whereas survivors did not differ from controls (P = 0.322). CONCLUSIONS: The observed dissociation of DHEA and DHEAS in septic shock contradicts the previous concept of sepsis-associated DHEA deficiency. Increased DHEA levels may maintain the balance between glucocorticoid- and DHEA-mediated immune and vascular effects. However, most severe disease and mortality is associated with an increased cortisol to DHEA ratio, which may represent a novel prognostic marker in septic shock.     

Circulating concentrations of dehydroepiandrosterone and dehydroepiandrosterone sulfate during puberty.

In order to quantitate the chronological change in circulating dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DS) levels during the period of sexual maturation, serum DHEA and DS concentration (3-5 PM) in 76 boys and 65 girls (ages 8 to 15) as well as in adult male and female subjects were measured by a specific and sensitive radioimmunoassay technique. Our data show a progressive and parallel increase in serum DHEA and DS concentrations in boys, and adult male levels were reached earlier for DHEA (age 13) than for DS (age 14). From age 8 to adult male, there was a 2.6-fold increase in DHEA (1.52 plus or minus 0.16 ng/ml to 3.91 lus or minus 0.34 ng/ml) and a 7.7-fold increase in DS (0.40 plus or minus 0.08 mug/ml to 3.09 plus or minus 0.36 mug/ml).The rise of DHEA and DS was not in a parallel fashion in girls; while DS rose progressively, DHEA showed an abrupt increase between 11 and 12 yr of age. Adult female range was reached by age 12 for DHEA and by age 15 for DS. From age 8 to adultfemale there was a 2.3-fold increase in DHEA (1.93 plus or minus 0.19 ng/ml to 4.49 plus or minus 0.76 ng/ml) and a 7.5-fold increase in DS (0.29 PLUS OR MINUS 0.05 MUg/ml to 2.17 plus or minus 0.34 mug/ml). The role of increased adrenal androgens inthe sexual development during early stages of puberty is discussed.     

男性冠心病患者血清硫酸脱氢表雄酮浓度的分析

目 的 观察血清硫酸脱氢表雄酮(DHEAS)浓度的变化与男性冠状动脉粥样硬化的关系。方法 通过冠状动脉造影检查和酶联免疫吸附测定法,比较冠状动脉造影异常男性患者与对照者血清DHEAS浓度的变化。结果冠状动脉造影狭窄程度≥50％的男性患者中血清DHEAS的浓度与对照组比较明显降低(P<0.01),而且随着冠状动脉狭窄程度≥50％病变冠状动脉数目的增多,DHEAS下降程度更为明显。结论血清DHEAS降低可能是导致男性冠心病发病率显著升高的重要因素,监测血清DHEAS含量有助于判断冠心病病变程度。