DHEA) And Its Sulfate Levels Research Articles

Sex-specific association of serum dehydroepiandrosterone and its sulfate levels with osteoporosis in type 2 diabetes.

This study is to investigate the relation between serum dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) levels and the risk of osteoporosis in patients with T2DM. This cross-sectional study involved 938 hospitalized patients with T2DM. Linear regression models were used to explore the relationship between DHEA and DHEAS and the BMD at different skeletal sites. Multinominal logistic regression models and the restricted cubic spline (RCS) were used to evaluate the associations of DHEA and DHEAS with the risks of osteopenia and/or osteoporosis. In postmenopausal women with T2DM, after adjustment for confounders including testosterone and estradiol, DHEA showed a significant positive correlation with lumbar spine BMD (P = 0.013). Moreover, DHEAS exhibited significant positive correlations with BMD at three skeletal sites: including femoral neck, total hip, and lumbar spine (all P < 0.05). Low DHEA and DHEAS levels were associated with increased risk of osteopenia and/or osteoporosis (all P < 0.05) and the risk of osteoporosis gradually decreased with increasing DHEAS levels (P overall = 0.018, P-nonlinear = 0.559). However, DHEA and DHEAS levels in men over the age of 50 with T2DM were not associated with any of above outcomes. In patients with T2DM, independent of testosterone and estradiol, higher DHEA and DHEAS levels are associated with higher BMD and lower risk of osteopenia/osteoporosis in postmenopausal women but not men over the age of 50.

Dehydroepiandrosterone and dehydroepiandrosterone-sulfate: Biomarkers of pregnancy and of fetal health

Dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) are important estrogen precursors, secreted mainly by the adrenal cortex. At late gestation, both DHEA and DHEAS (DHEA(S)) are produced at high concentrations in some species due to the developing fetal adrenal gland. Failure in DHEAS increase during late gestation can indicate fetal death, which prompts its use as a biomarker of pregnancy and fetal health in wildlife. Here, we review the most common non-invasive biomarkers of reproduction in wildlife, the molecular mechanisms of DHEAS synthesis and action during gestation, in addition to the advantages and limitations of incorporating DHEA(S) in these studies. Using previously published data, we tested the specificity and sensitivity of fecal DHEAS as a predictor of successful gestation in four captive primate species (orangutans (Pongo pygmaeus), siamangs (Symphalangus syndactylus), Japanese macaques (Macaca fuscata), and howler monkeys (Alouatta caraya)). Using data from non-pregnant/non-lactating females, we set a threshold on fecal DHEAS levels for detecting successful pregnancy per species, controlling for age and housing condition (social vs single). We found that DHEAS had 100% specificity for all species (non-pregnant samples were below the threshold for pregnancy), and 100% sensitivity for Japanese macaques housed individually, and for orangutan and siamangs (all samples from successful pregnancies were above the threshold, and all samples from stillbirth were below the threshold). However, the sensitivity was 80% in howler monkeys and 50% in Japanese macaques housed socially. Our preliminary results indicate that, while DHEAS is a promising biomarker of fetal health, it is limited to late gestation and to some species. We suggest increasing the sample size to calculate the pregnancy threshold per species and to test multiple samples from the same individual when using this method.

Serum DHEA and Its Sulfate Are Associated With Incident Fall Risk in Older Men: The MrOS Sweden Study.

The adrenal-derived hormones dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) are the most abundant circulating hormones and their levels decline substantially with age. Many of the actions of DHEAS are considered to be mediated through metabolism into androgens and estrogens in peripheral target tissues. The predictive value of serum DHEA and DHEAS for the likelihood of falling is unknown. The aim of this study was, therefore, to assess the associations between baseline DHEA and DHEAS levels and incident fall risk in a large cohort of older men. Serum DHEA and DHEAS levels were analyzed with mass spectrometry in the population-based Osteoporotic Fractures in Men study in Sweden (n = 2516, age 69 to 81 years). Falls were ascertained every 4 months by mailed questionnaires. Associations between steroid hormones and falls were estimated by generalized estimating equations. During a mean follow-up of 2.7 years, 968 (38.5%) participants experienced a fall. High serum levels of both DHEA (odds ratio [OR] per SD increase 0.85; 95% CI, 0.78 to 0.92) and DHEAS (OR 0.88, 95% CI, 0.81 to 0.95) were associated with a lower incident fall risk in models adjusted for age, BMI, and prevalent falls. Further adjustment for serum sex steroids or age-related comorbidities only marginally attenuated the associations between DHEA or DHEAS and the likelihood of falling. Moreover, the point estimates for DHEA and DHEAS were only slightly reduced after adjustment for lean mass and/or grip strength. Also, the addition of the narrow walk test did not substantially alter the associations between serum DHEA or DHEAS and fall risk. Finally, the association with incident fall risk remained significant for DHEA but not for DHEAS after simultaneous adjustment for lean mass, grip strength, and the narrow walk test. This suggests that the associations between DHEA and DHEAS and falls are only partially mediated via muscle mass, muscle strength, and/or balance. In conclusion, older men with high DHEA or DHEAS levels have a lesser likelihood of a fall. © 2018 American Society for Bone and Mineral Research.

Testosterone Increases Circulating Dehydroepiandrosterone Sulfate Levels in the Male Rhesus Macaque

The adrenal steroid dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) are two of the most abundant hormones in the human circulation. Furthermore, they are released in a circadian pattern and show a marked age-associated decline. Adult levels of DHEA and DHEAS are significantly higher in males than in females, but the reason for this sexual dimorphism is unclear. In the present study, we administered supplementary androgens [DHEA, testosterone and 5α-dihydrotestosterone (DHT)] to aged male rhesus macaques (Macaca mulatta). While this paradigm increased circulating DHEAS immediately after DHEA administration, an increase was also observed following either testosterone or DHT administration, resulting in hormonal profiles resembling levels observed in young males in terms of both amplitude and circadian pattern. This stimulatory effect was limited to DHEAS, as an increase in circulating cortisol was not observed. Taken together, these data demonstrate an influence of the hypothalamo-pituitary–testicular axis on adrenal function in males, possibly by sensitizing the zona reticularis to the stimulating action of adrenocorticopic hormone. This represents a plausible mechanism to explain sex differences in circulating DHEA and DHEAS levels, and may have important implications in the development of hormone therapies designed for elderly men and women.

AB1428-HPR Fatigue in patients with quiescent systemic lupus erythematosus: The role of dehydroepiandrosterone sulfate

BackgroundFatigue is a major problem in systemic lupus erythematosus (SLE). In some patient groups, associations between fatigue and low levels of dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) have been found....

Elevated Cortisol Level and Cortisol/DHEAS Ratio in Schizophrenia as Revealed by Low-Dose Dexamethasone Suppression Test

Earlier studies have used the dexamethasone (DEX) suppression test (DST) to investigate the hypothalamic- pituitary-adrenal (HPA) function in schizophrenia, although the findings are controversial. Recently there has been an increased interest in the role of dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) in HPA axis function. Several studies have investigated basal DHEA(S) levels and cortisol/DHEA(S) ratios in schizophrenia patients, while no attempts have been made to investigate DHEA(S) level in response to the DEX administration. We aimed to compare the post- DEX cortisol and DHEAS levels and the cortisol/DHEAS ratio between schizophrenia patients and healthy controls. Here we administered the DST to 43 patients with schizophrenia and 37 age- and sex-matched healthy controls. Plasma cortisol levels, serum DHEAS levels, and cortisol/DHEAS ratio after administration of 0.5 mg of DEX were compared between the two groups. Schizophrenia patients showed significantly higher cortisol level and cortisol/DHEAS ratio than controls, while DHEAS levels were not significantly different between groups. These results suggest that besides the cortisol level, cortisol/DHEAS ratio as assessed with the DST might reflect abnormal HPA axis function in schizophrenia.

Suppression of plasma androgen levels with a combination therapy of depot-estrogen (Turisteron) and Dexamethasone in patients with prostatic cancer.

Treatment of patients with prostatic cancer with a combination of 1-2 mg depot-estrogen (ethinylestradiol sulfonate = Turisteron) per week and 1 mg dexamethasone per day suppressed the mean testosterone (T) level to 2.8% (0.53 nmol/l), the free T to 0.8% (1.9 pmol/l) and the adrenal androgens (AA) -- androstenedione (A), dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) -- to more than 40% of the initial values. Treatment with Turisteron alone (2 mg per week) did not change the DHEA and DHEAS levels but decreased plasma A concentration to 65% (2.96 nmol/l) of the initial values.

Altered DHEA and DHEAS Response to Exercise in Healthy Older Adults

Dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) are hormones produced by the adrenal cortex that decline in concentration with age. Decreased DHEA levels are associated with age-related disease and oxidative stress but might be increased in younger adults by exercise. Studies are presented assessing the response of DHEA and DHEAS to varied-intensity exercise in older age. DHEA increased significantly in young adults (14.5 +/- 6.1 ng/ml rising to 21.1 +/- 7.5 ng/ml; p < .01), whereas DHEAS decreased significantly (2.56 +/- 1.11 microg/ml falling to 1.90 +/- 0.8 microg/ml; p < .05), after submaximal exercise. DHEA and DHEAS levels were significantly lower in older adults than in younger adults (p < .01), and there was no observed response of either hormone to exercise in older adults. Lipoprotein protein carbonylation is presented as a measure of oxidative status and significantly decreased in younger adults postexercise. Participants with higher DHEA postexercise had lower LDL protein carbonyl concentrations (Pearson's coefficient -.409, p < .05).

Association of CYP3A7*1C and Serum Dehydroepiandrosterone Sulfate Levels in Women with Polycystic Ovary Syndrome

Adrenal androgen excess is common in polycystic ovary syndrome (PCOS) and appears to be heritable. CYP3A7 metabolizes dehydroepiandrosterone and its sulfate (DHEAS). A promoter variant, CYP3A7*1C, which results in persistent expression in adults, was associated with reduced DHEAS levels in a previous study, which led us to consider CYP3A7*1C as a modulator of adrenal androgen excess in patients with PCOS. The objective was to replicate the association between CYP3A7*1C and reduced DHEAS levels in PCOS patients and assess its possible role in modulating testosterone levels. Women with and without PCOS were genotyped for CYP3A7*1C, and this variant was tested for association with DHEAS and total and free testosterone. Subjects were recruited from the reproductive endocrinology clinic at the University of Alabama at Birmingham; controls were recruited from the surrounding community. Genotyping took place at Cedars-Sinai Medical Center (Los Angeles, CA). A total of 287 white women with PCOS and 187 controls were studied. CYP3A7*1C genotype, PCOS risk, and androgen levels were measured. PCOS subjects who carried the CYP3A7*1C variant had lower levels of serum DHEAS and total testosterone (P = 0.0006 and 0.046, respectively). The variant was not associated with PCOS risk. This study replicated prior work of the association of CYP3A7*1C and decreased DHEAS in a different population of young PCOS women, providing further genetic evidence that CYP3A7 plays a potential role in modulation of DHEAS levels. Adult expression of CYP3A7 may modify the PCOS phenotype by ameliorating adrenal androgen excess.

Abstract 4177: High Serum Dehydroepiandrosterone Sulfate Levels are Strikingly Associated with Less Mortality in Men: 27-Year Follow-Up Study

Background: Dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) are secreted adrenal steroids. DHEAS concentrations decline with aging. Supplementary use of DHEAS is common nowadays with a hope of longevity. But, there has been no data available. We investigated whether DHEAS levels could predict survival in humans. Methods: A total of 940 subjects (396 men, 544 women), aged 21 to 88, underwent a health examination in a community-based cohort in 1978–1979. In all subjects, baseline DHEAS measured by radioimmunoassay, and they were followed until 2005. Results: DHEAS levels were higher in men than in women and decreased with aging in both sexes. In a Cox proportional hazards model, age, DHEAS (inversely), systolic and diastolic blood pressure, and fasting plasma glucose were significantly associated with mortality in men. Of these variables, elevated DHEAS levels were the strongest predictor of survival after adjustments for age, systolic blood pressure, and fasting plasma glucose. Although elevated DHEAS levels were significantly related to survival in women, the significance disappeared after adjustment for age. DHEAS levels in men were classified into tertiles: group1 &lt;130, group2 130≤-&lt;200, group3 ≥200 ng/ml. Only 74.4% of subjects in the lowest DHEAS tertiles survived compared with more than 93.4% in the highest DHEAS tertiles, after adjustments for age and possible confounding factors (Hazard ratio:0.206; 95%C.I. 0.067– 0.630, p&lt;0.01). Conclusions: This study is the first demonstration of the favorable effect survival on a DHEAS in men in a 27-year prospective study.

Infantile acne as the initial sign of an adrenocortical tumor

A 23-month-old boy with persistent acne since 6 months of age had signs of virilization and accelerated growth. Hormone evaluation indicated increased levels of dehydroepiandrosterone (DHEA) and testosterone. Ultrasound and abdominal computed tomographic scan revealed a large adrenal mass consistent with an adrenocortical tumor. The patient underwent surgical excision of the well-encapsulated tumor with normalization of his hormones and no subsequent recurrence. Although rare, childhood adrenocortical tumors have a poor prognosis, with the majority of tumors having regional and metastatic disease. Because early diagnosis and complete surgical excision improve prognosis, children with refractory infantile acne should be evaluated for signs of virilization and accelerated growth. Laboratory evaluation should include luteinizing hormone, follicle-stimulating hormone, total and free testosterone cortisol, DHEA, and its sulfate (DHEA-S). Elevated levels of DHEA and DHEA-S should prompt an aggressive diagnostic evaluation for an adrenocortical tumor.

Effects of Dehydroepiandrosterone Replacement Therapy on Bone Mineral Density in Older Adults: A Randomized, Controlled Trial

Dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) decrease with aging and are important androgen and estrogen precursors in older adults. Declines in DHEAS with aging may contribute to physiological changes that are sex hormone dependent. The aim was to determine whether DHEA replacement increases bone mineral density (BMD) and fat-free mass. A randomized, double-blinded, controlled trial was conducted at an academic research institution. Participants were 70 women and 70 men, aged 60-88 yr, with low serum DHEAS levels. The intervention was oral DHEA 50 mg/d or placebo for 12 months. BMD, fat mass, and fat-free mass were measured before and after intervention. Intent-to-treat analyses revealed trends for DHEA to increase BMD more than placebo at the total hip (1.0%, P = 0.05), trochanter (1.2%, P = 0.06), and shaft (1.2%, P = 0.05). In women only, DHEA increased lumbar spine BMD (2.2%, P = 0.04; sex-by-treatment interaction, P = 0.05). In secondary compliance analyses, BMD increases in hip regions were significant (1.2-1.6%; all P < 0.02) in the DHEA group. There were no significant effects of DHEA on fat or fat-free mass in intent-to-treat or compliance analyses. DHEA replacement therapy for 1 yr improved hip BMD in older adults and spine BMD in older women. Because there have been few randomized, controlled trials of the effects of DHEA therapy, these findings support the need for further investigations of the benefits and risks of DHEA replacement and the mechanisms for its actions.

Plasma levels of 7-hydroxylated dehydroepiandrosterone (DHEA) metabolites and selected amino-thiols as discriminatory tools of Alzheimer's disease and vascular dementia.

The early differential diagnosis of Alzheimer's disease (AD) remains still problematic. We developed a laboratory test enabling us to distinguish patients with AD from those with vascular dementia (VD) and healthy subjects. The AD group consisted of 22 women and 18 men. The VD group consisted of 16 women and 8 men. Age-matched controls consisted of 12 women and 9 men. Plasma pregnenolone sulfate (PregS), dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) were determined by radioimmunoassay. 17-Hydroxypregnenolone (17Preg) and 7-hydroxylated metabolites of DHEA (7alphaDHEA, 7betaDHEA) were determined by radioimmunoassay after separation by high performance liquid chromatography (HPLC). Homocysteine (Hcy), cysteine (Cys), cysteinylglycine (Cysgly) and glutathione (GSH) were measured by HPLC. The ANOVA results of significant between-group differences were as follows: The PregS and the 17-Preg and DHEAS levels were independent from the diagnosis. The 7alphaDHEA levels significantly depended on the sex (p < 0.05) and diagnosis (p < 0.01). Amino-thiols were influenced by the diagnosis (p < 0.01, p = 0.0541, p < 0.01 and p = 0.0536 for Cys, Hcy, Cysgly and GSH, respectively). Using a stepwise backward regression analysis, the following parameters were obtained: X = 11.5 + 4.03 x sex +1.09 x Hcy + 0.190 x PregS - 4.76 x DHEAS + 3.00 x DHEA - 34.3 x 77alphaDHEA - 0.885 x Cysgly from which P-value as a discriminator was calculated according to the formula: P = 1/(1 + e(-x)). Then, for P > 0.5, a subject was considered as AD-positive (with 89% correct prediction). The opportunity of early differential diagnosis of AD should help physicians to use suitable treatment for retardation of pathological processes.

Low dehydroepiandrosterone and ischemic heart disease in middle-aged men: prospective results from the Massachusetts Male Aging Study.

The adrenal steroid dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) have been characterized as "protective" against ischemic heart disease (IHD), especially in men, on the basis of sparse epidemiologic evidence. The authors used data from the Massachusetts Male Aging Study, a random sample prospective study of 1,709 men aged 40-70 years at baseline, to test whether serum levels of DHEA or DHEAS could predict incident IHD over a 9-year interval. At baseline (1987-1989) and follow-up (1995-1997), an interviewer-phlebotomist visited each subject in his home to obtain comprehensive health information, body measurements, and blood samples for hormone and lipid analysis. Incident IHD between baseline and follow-up was ascertained from hospital records and death registries, supplemented by self-report and evidence of medication. In the analysis sample of 1,167 men, those with serum DHEAS in the lowest quartile at baseline (<1.6 microg/ml) were significantly more likely to incur IHD by follow-up (adjusted odds ratio = 1.60, 95 percent confidence interval: 1.07, 2.39; p = 0.02), independently of a comprehensive set of known risk factors including age, obesity, diabetes, hypertension, smoking, serum lipids, alcohol intake, and physical activity. Low serum DHEA was similarly predictive. These results confirm prior evidence that low DHEA and DHEAS can predict IHD in men.

Hippocampal Perfusion and Pituitary-Adrenal Axis in Alzheimer’s Disease

The hippocampus is involved in Alzheimer’s disease (AD) and regulates the hypothalamus-pituitary-adrenal axis (HPAA). Enhanced cortisol secretion has been reported in AD. Increased cortisol levels affect hippocampal neuron survival and potentiate β-amyloid toxicity. Conversely, dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) are believed to antagonize noxious glucocorticoid effects and exert a neuroprotective activity. The present study was aimed at investigating possible correlations between hippocampus perfusion – evaluated by SPECT – and HPAA function in AD. Fourteen patients with AD and 12 healthy age-matched controls were studied by ^99mTc-HMPAO high-resolution brain SPECT. Plasma adrenocorticotropin, cortisol, and DHEAS levels were determined at 2.00, 8.00, 14.00, 20.00 h in all subjects and their mean values were computed. Cortisol/DHEAS ratios (C/Dr) were also calculated. Bilateral impairment of SPECT hippocampal perfusion was observed in AD patients as compared to controls. Mean cortisol levels were significantly increased and DHEAS titers were lowered in patients with AD, as compared with controls. C/Dr was also significantly higher in patients. Using a stepwise procedure for dependent SPECT variables, the variance of hippocampal perfusional data was accounted for by mean basal DHEAS levels. Moreover, hippocampal SPECT data correlated directly with mean DHEAS levels, and inversely with C/Dr. These data show a relationship between hippocampal perfusion and HPAA function in AD. Decreased DHEAS, rather than enhanced cortisol levels, appears to be correlated with changes of hippocampal perfusion in dementia.

Serum dehydroepiandrosterone sulfate concentration and thyroid cancer risk: a matched case control study.

In animal models of carcinogenesis, pharmacological doses of dehydroepiandrosterone (DHEA) treatment appear to reduce the incidence of chemically induced thyroid cancers. DHEA and its sulfate (DHEA-S) are secreted in approximately equal amounts, but serum levels of DHEA-S are 300-500 times higher and have no diurnal variation when compared to DHEA. The hypothesis that serum concentrations of DHEA-S may be associated with thyroid cancer risk was tested in a population-based prospective case control study. Data from the practically complete nationwide Cancer Registry of Norway were linked to the data file of a serum bank comprising blood samples from 300,000 Norwegian men and women obtained through national health surveys. A total of 113 donors, who during the years after blood sampling received a diagnosis of thyroid cancer, were identified in the serum bank and were eligible for the study. Each case was matched with 3 controls. Serum levels of DHEA-S were determined blindly. Controls were divided into tertiles, and odds ratios between cases and controls were determined relative to the group with the lowest serum DHEA-S level. The risk of developing thyroid cancer was determined in women 50 years of age or older, in women below age 50, in men, and in the subgroup of 77 cases who had morphologically verified papillary thyroid cancer. No significant association between prediagnostic serum DHEA-S concentrations and thyroid cancer risk was observed. These data indicate that DHEA-S within physiological concentrations does not reduce the risk of thyroid cancer.

Neuropsychiatric Function and Dehydroepiandrosterone Sulfate in Elderly Women: A Prospective Study

Background: Though among the most abundant human steroid hormones, the physiologic role of dehydroepiandrosterone and its sulfate (DHEAS) is not known. Our goal was to determine if DHEAS is associated with cognition and mood in older women, and if baseline DHEAS levels are predictive of cognitive decline. Methods: In a prospective cohort, we studied 394 randomly selected community-dwelling women, aged 65 years or older, currently enrolled in the Study of Osteoporotic Fractures. Subjects were administered a modified Mini-Mental State Exam, Trails B, Digit Symbol, and the Geriatric Depression Scale–Shortened (GDSS), at study onset and 4–6 years later. Serum was obtained at study initiation for DHEAS analysis. Results: DHEAS levels declined with age, as expected. There was no consistent association of DHEAS quartile or log DHEAS with any of the four outcomes, even after multivariate adjustment. Change in cognitive performance over time was not associated with DHEAS levels. Analysis of the 32 women without any detectable DHEAS compared to those with detectable levels revealed higher measures on the GDSS (mean score 3.4 ± 3.6 compared with 1.6 ± 2.3, p = .028) and a higher percentage with depression (21.7% compared with 4.6%, p = .001). Conclusions: Serum DHEAS is not a sensitive predictor of cognitive performance or decline on a selected neuropsychological battery in elderly community women; however, nondetectable levels may be associated with depression.

Dehydroepiandrosterone sulfate: a biomarker of primate aging slowed by calorie restriction.

The adrenal steroids, dehydroepiandrosterone (DHEA) and its sulfate (DHEAS), have attracted attention for their possible antiaging effects. DHEAS levels in humans decline markedly with age, suggesting the potential importance of this parameter as a biomarker of aging. Here we report that, as seen in humans, male and female rhesus monkeys exhibit a steady, age-related decline in serum DHEAS. This decline meets several criteria for a biomarker of aging, including cross-sectional and longitudinal linear decreases with age and significant stability of individual differences over time. In addition, the proportional age-related loss of DHEAS in rhesus monkeys is over twice the rate of decline observed in humans. Most important is the finding that, in rhesus monkeys, calorie restriction, which extends life span and retards aging in laboratory rodents, slows the postmaturational decline in serum DHEAS levels. This represents the first evidence that this nutritional intervention has the potential to alter aspects of postmaturational aging in a long-lived species.

Cortisol, dehydroepiandrosterone (DHEA), and DHEA sulfate in the cerebrospinal fluid of man: relation to blood levels and the effects of age.

The relation between blood and cerebrospinal fluid (CSF) concentrations of cortisol, dehydroepiandrosterone (DHEA), and its sulfate (DHEAS) was measured in 62 subjects aged 3-85 yr old, fitted with ventriculo-peritoneal or lumbar-peritoneal shunts for a variety of diagnoses. There were 36 males and 36 females. Forty-eight subjects were not taking exogenous corticosteroids; the other 14 were receiving either systemic or local steroids. A single sample of blood and CSF was taken from each subject within 10 min for measurement of cortisol, DHEA, and DHEAS. The proportional levels of cortisol (5.8%) and DHEA (5.4%) in the CSF compared with those in the blood were similar in subjects not taking steroids. However, CSF DHEAS levels were only 0.15% of those in the blood. Because DHEAS blood levels were so much greater than DHEA, DHEAS in the CSF was still higher than DHEA despite the reduced penetration of the sulfated steroid. The blood/CSF ratios were similar in subjects taking steroids. There were significant correlations in steroid-free subjects between blood and CSF levels for DHEA (r = 0.65) and DHEAS (r = 0.88) but not for cortisol (r = 0.26). Steroid treatment significantly lowered blood cortisol, DHEA and DHEAS, and CSF DHEA, but not CSF cortisol or DHEAS compared with an age- and sex-matched sample of steroid-free subjects. In steroid-free adults (18 yr and over; n = 37), blood cortisol showed no age-related change. However, CSF cortisol was markedly raised in a proportion of steroid-free subjects over the age of 60 yr. Levels of corticoid-binding globulin in plasma did not alter with age. As expected, there were significant age-related decrements in both blood DHEA and DHEAS. CSF DHEA (r = 0.42) and CSF DHEAS (r = 0.39) were significantly negatively correlated with age. In steroid-free juveniles (n = 11) there were no age-related changes in either blood or CSF cortisol, but significant increases with age in DHEA and DHEAS in both blood and CSF. Calculation of the cortisol/DHEA and cortisol/ DHEAS molar ratios in the CSF showed both to be raised in the very young (3-8 yr) and the elderly (60 yr and over) by a factor of 4-5 compared with young adults aged 18-39. There were no sex differences in any of the parameters measured. These findings show that the relation between levels in the blood and CSF differ for each of these three neuroactive steroids. The brain is exposed to relatively high levels of DHEA and DHEAS during later childhood and early adulthood but to relatively or absolutely high levels of cortisol during infancy and older age. In view of the known antiglucocorticoid action of DHEA and DHEAS, and the direct action of these steroids on membrane-bound transmitter events (such as gamma-aminobutyric acidA receptors), these changes may have important implications for age-related alterations in brain function.

Longitudinal Study of Adrenocortical Function following Allogeneic Bone Marrow Transplantation in Children

Basal serum concentrations of cortisol, dehydroepiandrosterone (DHA) and its sulfate (DHAS), 4-androstene-3,17-dione (A4) and 17 alpha-hydroxyprogesterone (17OHP) were measured yearly in children treated with bone marrow transplantation (BMT) with or without preceding total body irradiation (TBI). Age-matched controls were used for comparison. ACTH stimulation tests were performed in the patients before and after treatment. However, in the samples taken before BMT only cortisol was measured. Basal posttreatment cortisol levels were subnormal in TBI-treated boys (n = 14, aged 5-17 years at BMT) during the adrenarcheal period (7-14 years) but became normal afterwards. All other groups had normal cortisol values. Treatment neither affected basal levels nor the ACTH-induced increment (delta-value) of cortisol. In the boys treated with TBI, normal basal levels of 17OHP and adrenal androgens were found with the exception of decreased DHA levels in the postadrenarcheal boys. However, the delta-17OHP values and had an abnormal age relation and were significantly higher than in the patients not treated with TBI. In the patients not treated with TBI (6 boys aged 2-17 years) normal responses were found for 5 years or more after treatment. In female patients treated with TBI (n = 12, aged 1-16 years) circulating levels of DHA, DHAS and A4 were significantly decreased up to 5 years or more following treatment. It is concluded that after TBI, the cortisol homeostasis is maintained at the cost of reduced adrenal androgen secretion.