Dehydroepiandrosterone In Patients Research Articles

Correlation of dehydroepiandrosterone with diabetic nephropathy and its clinical value in early detection.

Aims/IntroductionThis study was carried out to assess the association of dehydroepiandrosterone (DHEA) with diabetic nephropathy (DN) in patients with type 2 diabetes mellitus to better predict the progression of diabetic nephropathy.Materials and MethodsA total of 1,082 patients with type 2 diabetes mellitus in the Department of Endocrinology and Metabolism of Tianjin Medical University General Hospital were enrolled in this study, and grouped for comparison. The effect of serum DHEA on DN was evaluated by multivariate logistic regression analysis, and receiver operating characteristic curves were established to explore the optimal concentration of DHEA in patients with DN and non‐DN.ResultsDHEA was significantly decreased in patients with DN (P < 0.001). The prevalence of DN was significantly higher in the low DHEA quartile than in the other quartiles (P < 0.001). Spearman‐related analysis showed that DHEA levels were negatively correlated with patient age, course of diabetes, systolic blood pressure, blood creatinine, uric acid, urine albumin‐to‐creatinine ratio, 24‐h urine microalbumin, 24‐h urine protein quantification and glomerular filtration rate, and positively correlated with body mass index, total cholesterol and low density lipoprotein. Logistic regression analysis showed that the effect of DHEA on DN was statistically significant (P < 0.001). The receiver operating characteristic curve showed that the sensitivity was 81.4%, the specificity was 70% and the area under the curve was 0.812 when the optimal cut‐off value was 1,640 (pg/mL).ConclusionDHEA is significantly associated with DN and might be a protective factor for DN, and is important for the prediction of DN.

Salivary cortisol and dehydroepiandrosterone in patients with recurrent aphthous stomatitis

Background: One of the most frequently encountered diseases of oral cavity is recurrent aphthous stomatitis (RAS). The present study was conducted to assess salivary cortisol and dehydroepiandrosterone as oral biomarkers to determine stress in patients with recurrent aphthous stomatitis. Materials & Methods: 52 patients of RAS of both genders were divided into 2 groups. Group I comprised of patients with RAS and group II had age matched healthy control. 2 mL of unstimulated whole saliva was collected and salivary cortisol and DHEA levels were measured using ELISA kit. Results: Group I had 20 males and 32 females and group II had 21 males and 31 females. 85% in group I and 26% in group II had salivary cortisol level >3 ng/ml and 15% in group I and 74% in group II had between 1.2–3 ng/mL. The difference was significant (P

Impact of physical or sexual childhood abuse on plasma DHEA, DHEA-S and cortisol in a low-dose dexamethasone suppression test and on cardiovascular risk parameters in adult patients with major depression or anxiety disorders

While the impact of childhood trauma on basal and dynamic cortisol regulation has widely been studied, the most abundant steroid hormones dehydroepiandrosterone (DHEA) and its sulphated derivative DHEA-S have received little attention in this context. One-hundred in-door patients suffering from major depression or an anxiety disorder filled in the Childhood Trauma Questionaire. A low dose dexamethasone suppression test (DST) measuring DHEA, DHEA-S and cortisol was performed. Furthermore, various cardiovascular risk parameters were measured. Forty-six percent of the patients reported a history of substantial physical or sexual childhood abuse. However, no significant differences in plasma DHEA or DHEA-S emerged in the DST between the traumatised group and the remaining patients. Basal plasma cortisol was significantly lower in the childhood trauma group. No impact of childhood trauma history on cardiovascular risk factor profile was detected. Current limited data about DHEA or DHEA-S in patients with childhood trauma are equivocal. Further study using more sophisticated assessment of trauma history and simultaneously measuring a multitude of putative biomarkers of traumatization are needed.

The effects of dehydroepiandrosterone (DHEA) in the treatment of depression and depressive symptoms in other psychiatric and medical illnesses: a systematic review.

International interest on the benefits of using the steroid hormone Dehydroepiandrosterone (DHEA) on various aspects of human health, including the regulation of mood, is increasing. This study aimed to review the scientific literature on the use of DHEA in the treatment of depression and depressive symptoms in other psychiatric and medical illnesses. PubMed, ISI Web of Knowledge and Virtual Health Library (VHL) databases were independently searched by two researchers using the following terms: depression, treatment, DHEA, and mood. Clinical studies were considered eligible when subjects were treated with DHEA and psychological assessments of depression were conducted. No time limits or language for this research were imposed. One 183 references were identified, and 22 references were selected to compose this review. Significant improvements related to the use of DHEA in patients with depression were observed, in addition to improvements in depressive symptoms in patients with schizophrenia, anorexia nervosa, HIV and adrenal insufficiency. No significant improvements were observed regarding depressive symptoms in patients with fibromyalgia; the results observed in patients with autoimmune diseases and healthy individuals remain contradictory. Although the selected studies demonstrated good methodological applications, most studies consisted of small samples, and only 3 studies were conducted in a young population. Therefore, we concluded that the studies published to date indicate promising results regarding the use of DHEA in the treatment of depression and depressive symptoms, especially in depression that is mild or resistant to conventional therapy.

DHEA pre-treated patients, poor responders to a first IVF (ICSI) cycle: clinical results

Purpose: To evaluate the effect of the premedication with dehydroepiandrosterone (DHEA) on the results of the in vitro fertilization (IVF) treatments in a group of women with evidence of diminished ovarian reserve. Materials and Methods: This experimental, prospective, pre-post study enrolled 29 patients with evidence of diminished ovarian reserve and poor-responders to a previous treatment. They received 75 mg/die of DHEA for a minimum of eight weeks; from the 18th day of the cycle before the stimulation with follicle stimulating hormone (FSH), they took trans-dermal estradiol (E2) (50 mcg every other day). The protocol of the stimulation consisted of a short cycle with follicle stimulating hormone receptor-human menopausal gonadrotropin (FSHr-HMG) and low doses of gonadotropin releasing hormone agonist (GnRH-a) (0.05 mg/die). The study was carried out comparing the results obtained respectively with the pre-DHEA and the post-DHEA treatments. Results: The comparative analysis of the results showed a significant increase in the number of the retrieved oocytes (p p = 0.02) and a reduction of cancelled cycles (p = 0.03). Moreover, after the treatment with DHEA, there was an increase, though non-significant, in the number of embryos, in the fertilization rate, and in the number of pregnancies. Conclusions: This study confirms the beneficial effects of DHEA in patients who resulted poor responders to IVF treatments. Therefore, DHEA appears to be an effective treatment for age related sub-fertility.

Measurements of Serum DHEA and DHEA Sulphate Levels Improve the Accuracy of the Low-Dose Cosyntropin Test in the Diagnosis of Central Adrenal Insufficiency

The diagnosis of central adrenal insufficiency (AI) continues to be challenging, especially when it is partial. We have recently demonstrated the value of measuring serum dehydroepiandrosterone sulfate (DHEA-S) in establishing the diagnosis of central AI. The current investigation examined the added value of measuring serum dehydroepiandrosterone (DHEA) levels during low-dose (1 μg) cosyntropin (LDC) stimulation in patients suspected to have central AI. Baseline and LDC-stimulated cortisol, DHEA, and DHEA-S were measured preoperatively in 155 consecutive patients with pituitary masses and 63 healthy subjects. Hypothalamic-pituitary adrenal (HPA) function was normal (NL-HPA) in 97 of the patients and was impaired (impaired HPA) in 58 patients. Patients with NL-HPA underwent surgical removal of the sellar masses and received no glucocorticoids before, during, or after surgery. Baseline and LDC-stimulated serum cortisol, DHEA, and DHEA-S in patients with NL-HPA were similar to those of normal subjects. In contrast, patients with impaired HPA had lower baseline and LDC-stimulated serum cortisol, DHEA, and DHEA-S levels. There were 18 subjects in the latter group whose LDC-stimulated serum cortisol levels were greater than 18.0 μg/dl. In those 18 subjects, baseline and LDC-stimulated DHEA and DHEA-S levels were similar to the whole group of patients with impaired HPA function. The molar ratio of cortisol to DHEA did not change with LDC stimulation in normal subjects and those with NL-HPA. In contrast, patients with impaired HPA had a higher baseline cortisol to DHEA molar ratio that increased further with LDC stimulation. Patients with impaired HPA function have a more severe loss in DHEA secretion than that of glucocorticoids. Measurements of serum DHEA levels during LDC simulation provide additional valuable information that improves the diagnostic accuracy of LDC in patients suspected to have central AI. We recommend the inclusion of DHEA and DHEA-S measurements in the laboratory assessment of HPA function.

Low serum levels of dehydroepiandrosterone may cause deficient IL-2 production by lymphocytes in patients with systemic lupus erythematosus (SLE).

The principal cause of IL-2 deficiency, a common feature of both murine lupus and human SLE, remains obscure. Recent studies of our own as well as others have shown that dehydroepiandrosterone (DHEA), an intermediate compound in testosterone synthesis, significantly up-regulates IL-2 production of T cells, and that administration of exogenous DHEA or IL-2 via a vaccinia construct to murine lupus dramatically reverses their clinical autoimmune diseases. Thus, we have examined serum levels of DHEA in patients with SLE to test whether abnormal DHEA activity is associated with IL-2 deficiency of the patients. We found that nearly all of the patients examined have very low levels of serum DHEA. The decreased DHEA levels were not simply a reflection of a long term corticosteroid treatment which may cause adrenal atrophy, since serum samples drawn at the onset of disease, which are devoid of corticosteroid treatment, also contained low levels of DHEA. In addition, exogenous DHEA restored impaired IL-2 production of T cells from patients with SLE in vitro. These results indicate that defects of IL-2 synthesis of patients with SLE are at least in part due to the low DHEA activity in the serum.

Substitution mit Nebennierensteroiden

Replacement with adrenal steroids comprises treatment with glucocorticoids, mineralocorticoids and adrenal androgen precursors, mainly in patients with adrenal insufficiency. Attention has also been directed to replacement treatment with glucocorticoids in critically ill patients or with dehydroepiandrosterone (DHEA) in elderly people with an age related decline of DHEA/DHEAS levels. Despite the use of current replacement concepts well-being is often not fully restored in patients with adrenal insufficiency. Innovations comprise the development of new delayed release glucocorticoid preparations that allow to better mimic the circadian cortisol secretion and may have the potential to improve the treatment of patients with adrenal insufficiency. Recent results from the CORTICUS study have not confirmed previous beneficial results and have led to restrictions in the use of hydrocortisone substitution therapy in patients with septic shock. Treatment with the androgen precursor DHEA in patients with adrenal insufficiency may improve quality of life. However, in patients with an age related decline of DHEA levels, the available evidence does not support the use of DHEA replacement as an anti aging treatment.

Lack of dehydroepiandrosterone in type I and II hereditary angioedema and role of danazol in steroid hormone conversion

Hereditary angioedema (HAE) is successfully treated with danazol, a therapeutic steroid compound. To investigate hormones of the hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal (HPG) axis in patients with HAE with and without danazol. We included 16 patients with type I HAE, nine patients with type II HAE, and 16 healthy subjects. Serum levels of adrenocorticotropic hormone (ACTH), cortisol, androstenedione, dehydroepiandrosterone (DHEA), free testosterone, and 17beta-oestradiol were measured. Serum levels of ACTH were markedly decreased in patients with type II HAE compared to the other groups (P < 0.001). Serum cortisol was similar between groups but danazol treatment decreased cortisol levels, particularly in women (P = 0.019). Serum levels of DHEA were significantly decreased in all patients with type I and II HAE compared to controls (P < 0.05), which was only partly dependent on prior danazol therapy as patients without danazol had also decreased serum levels of DHEA (P < 0.05). Furthermore, free testosterone serum levels were markedly increased in patients under danazol (P < 0.005) and the ratio of 17beta-oestradiol/free testosterone was significantly decreased in these patients (P < 0.005). This study demonstrated decreased DHEA in patients with type I and II HAE independent of danazol therapy, which was particularly evident in women. It also demonstrates that danazol induced a marked up-regulation of free testosterone in relation to precursors and downstream 17beta-oestradiol. In HAE, there seems to be a primary lack of the adrenal androgen DHEA.

Dehydroepiandrosterone and ageing.

Dehydroepiandrosterone (DHEA) is the major steroid produced by the adrenal zona reticularis and, in contrast to cortisol and aldosterone, its secretion declines with ageing. This has generated major interest in its putative role as an 'anti-ageing' hormone. However, it is not clear that the age-associated, physiological decline in DHEA secretion represents a harmful deficiency. DHEA exhibits its action mainly by conversion to sex steroids. In addition, DHEA has neurosteroidal properties and may exhibit direct action via specific binding sites on endothelial cells. There is convincing evidence for beneficial effects of DHEA in patients with adrenal insufficiency and future research will hopefully elucidate its role in patients receiving pharmacological glucocorticoid treatment. However, in healthy elderly subjects, current evidence from randomised, controlled trials does not justify the use of DHEA, with no major beneficial effects reported and, in addition, potentially adverse effects on sex steroid-dependent tumour growth need to be considered.

Serum dehydroepiandrosterone and DHEA-sulfate in patients with adult T-cell leukemia and human T-lymphotropic virus type I carriers

The serum levels of dehydroepiandrosterone (DHEA) and DHEA-sulfate (DHEA-S) were determined by radioimmunoassay in 38 patients with adult T-cell leukemia (ATL). Levels of serum DHEA and DHEA-S were also measured in 60 human T-lymphotropic virus type I (HTLV-I) carriers, and did not differ from those in 60 healthy control subjects. Serum levels in patients with ATL were lower than those in the age- and sex-matched healthy controls and in HTLV-I carriers with statistical significance. Serum DHEA and DHEA-S in male patients with acute and lymphoma-type ATL were 1.06 +/- 0.77 ng/ml and 245.8 +/- 192.9 ng/ml, respectively. Levels in male patients with chronic and smoldering-type ATL were 1.69 +/- 0.68 ng/ml and 477.6 +/- 251.5 ng/ml, respectively. Serum levels of DHEA and DHEA-S in patients with acute and lymphoma-type ATL were significantly lower than those in patients with chronic and smoldering-type ATL (P < 0.05). These data suggest that a decrease in serum levels of DHEA and DHEA-S may be associated with patients who have some clinical subtypes of ATL. Moreover, androgens may have a therapeutic role in patients with ATL, as administered in patients with hairy-cell leukemia. Because there is at present no curative chemotherapy for ATL, a trial combination of androgens and standard chemotherapy may be a reasonable therapeutic option in such patients.

A review of dehydroepiandrosterone (DHEA).

Dehydroepiandrosterone (DHEA) is quantitatively the most abundant hormone in humans and mammals, with a wide variety of physiological effects, including major regulatory effects upon the immune system. Two of the most striking aspects of DHEA are a steady decline in DHEA with age and a significant deficiency in DHEA in patients with several major diseases, including cancer, atherosclerosis, and Alzheimer's disease. The hormone is secreted in a non-sulfated (DHEA) and sulfated form (DHEA-S). The two are apparently interchangeable, and it appears likely that its physiological effects are achieved by derivative molecules that have yet to be identified.

Neurosteroids in cerebrospinal fluid in neurologic disorders

In order to investigate the role of “neurosteroids” in the central nervous system (CNS), cerebrospinal fluid (CSF) levels of dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) were determined by radioimmunoassay in 57 patients with various neurologic disorders and 26 patients with non-neurologic disorders. The content of CSF DHEA and DHEAS in patients with Guillain-Barré syndrome (GBS), and the content of CSF DHEAS in patients with carcinomatous meningitis were significantly higher as compared to non-neurological control patients. These changes may be explained by the breakdown of blood-nerve barrier in these disorders. A significant positive correlation was observed between DHEAS and total protein in CSF. In males but not females, a negative correlation was observed between CSF DHEAS and aging. The level of CSF DHEAS, but not DHEA, was significantly higher in males than in females.

Concentrations of total and free dehydroepiandrosterone in plasma and dehydroepiandrosterone in saliva of normal and hirsute women under basal conditions and during administration of dexamethasone/synthetic corticotropin

Using a specific and sensitive radioimmunoassay involving extraction with diethyl ether and chromatographic separation of steroids, we measured concentrations of salivary and plasma dehydroepiandrosterone (DHEA) in 22 women with normal ovulatory cycles (ages 18-45 years). Salivary DHEA values closely correlated with total and free DHEA in plasma. In the follicular phase the mean concentrations of salivary and plasma free DHEA were virtually equal [mean (SD): 0.61 (0.32) and 0.56 (0.34) nmol/L, respectively]. In the luteal phase, salivary DHEA slightly exceeded the plasma free DHEA [0.68 (0.40) vs 0.56 (0.38) nmol/L, P less than 0.01]. Also, during combined dexamethasone/synthetic corticotropin administration in 25 patients with androgenizing disorders and in 10 normal subjects (each in the follicular and luteal phases), the concentration of DHEA in saliva strongly correlated with total and free DHEA in plasma. During these dynamic tests, the mean concentrations of free DHEA in plasma and salivary DHEA in the hirsute women were significantly higher than the mean concentrations in the control women at all times before and after corticotropin infusion (P less than 0.05- less than 0.0001). In contrast, plasma total DHEA in patients exceeded nonhirsute values only at 15 min after corticotropin administration. In six of 25 patients total DHEA during combined administration of dexamethasone/synthetic corticotropin exceeded normal values by at least 2 SD. The response of salivary and free DHEA to synthetic corticotropin in this subgroup was also excessive.

Adrenal steroid responses to naloxone in polycystic ovarian disease.

In order to investigate the role of the adrenal gland in the pathogenesis of polycystic ovarian disease (PCOD), we evaluated the adrenal steroid response to an opiate receptor blockade. Six healthy menstruating volunteers and 6 patients with PCOD were given a saline or naloxone (4 mg i.v.) injection in the early follicular phase. Blood samples were taken prior to the injections and every 15-30 minutes in the following 2 hours. Cortisol, androstenedione (A) and dehydroepiandrosterone (DHA) plasma levels were determined by RIA after extraction (cortisol) and celite chromatography (A and DHA). While in controls naloxone increased only cortisol concentrations, in PCOD patients DHA plasma levels also were stimulated by the opiate receptor antagonist. In PCOD patients the increase of cortisol (p less than 0.05) and of DHA (p less than 0.001) levels resulted significantly higher than in controls. In both groups A plasma levels remained unchanged after naloxone administration. These data confirm that endogenous opioids exert an inhibitory control on the pituitary-adrenal axis. In PCOD patients the response to naloxone led to a hypersecretion of adrenal delta 5-androgens, which could account for the development of the syndrome.

The relationship of plasma 7α-hydroxy dehydroepiandrosterone to disease stage and adrenal androgens in breast cancer patients

The concentrations of 7α-hydroxy dehydroepiandrosterone ( 7α-hydroxy DHA) were measured in the plasma of patients presenting with different stages of breast cancer. The results were compared with the concentrations in control subjects and patients with benign breast disease. The concentrations of 7α-hydroxy DHA in plasma were also compared with the concentrations of dehydroepiandrosterone (DHA) and dehydroepiandrosterone sulphate (DHAS) in plasma. Plasma 7α-hydroxy DHA was lower in patients presenting with early disease without axillary node involvement than in the control or benign disease groups but no significant difference was found between the control or benign disease group and the early disease nodal positive group or advanced disease groups. Plasma 7α-hydroxy DHA was positively correlated with plasma DHA and, to a lesser extent, with plasma DHAS. The greater increases in plasma 7α-hydroxy DHA compared to plasma DHA in patients presenting with distant metastases and with large tumours were significantly different to the control and benign disease group but there was no significant difference between the early disease groups and the control and benign disease group. The greater increase in plasma 7α-hydroxy DHA compared to plasma DHAS in patients presenting with metastases was significantly different to the control group, but there was no significant difference in any of the other patient groups.