Plasma DHEA Research Articles

Effect Of Dehydroepiandrosterone Administration On Recovery Capacity During Training Session In Male Badminton Players

Dehydroepiandrosterone (DHEA), with its sulfate derivative DHEA-S, serves as a precursor of testosterone. In addition, DHEA-S has been shown to have a buffering action against stress, and was reduced under major stress conditions such as trauma and disease. However, its biological function on post-exercise recovery capacity has not been well investigated. PURPOSE: To determine the effect of DHEA administration on enhancing post-exercise recovery capacity during badminton-specific training program. METHODS: Sixteen well-trained male badminton players were balanced by body fat percentage and divided into two groups: DHEA (N=8, age: 19.89 ± 1.71 yrs, fat %= 13.51 ± 0.84) and Placebo (N =8, age: 19.75 ± 1.98, fat %= 13.08 ± 1.63) using a double blind study design. Baseline measurements were taken on Day 0, followed by the initial supplement administration. All subjects were taken supplement daily from Day 0 through Day 5 (DHEA group: 100 mg/day; Placebo group: flour placebo). Subjects performed a 6-day standard badminton-specific training program, which included a high-intensity shuttle run on Day 2. The visualized DOMS index and blood creatine kinase (CK) level were measured to evaluate recovery status. Plasma DHEA-S and total testosterone levels also were assessed as well. RESULTS: Plasma DHEA-S (Day 2 to Day 6) and total testosterone (Day 3 to Day 6) levels were significantly higher (p<0.05) in the DHEA group compared to placebo. In contrast, both DHEA-S and total testosterone levels dropped dramatically (p<0.05) after Day 3 following the high intensity shuttle run. For the recovery status, the DHEA group showed a significant reduction in visualized DOMS index on Days 3 & 6 (p<0.05) and statistical decreases in blood CK levels from Day 4 to Day 6 (p<0.05). CONCLUSIONS: In well-trained male badminton players, DHEA administration has a beneficial effect on improving post-exercise recovery capacity, possibly due to the buffering action of DHEA-S to further preventing muscle damage.

In rats, oral oleoyl-DHEA is rapidly hydrolysed and converted to DHEA-sulphate

BackgroundDehydroepiandrosterone (DHEA) released by adrenal glands may be converted to androgens and estrogens mainly in the gonadal, adipose, mammary, hepatic and nervous tissue. DHEA is also a key neurosteroid and has antiglucocorticoid activity. DHEA has been used for the treatment of a number of diseases, including obesity; its pharmacological effects depend on large oral doses, which effect rapidly wanes in part because of its short half-life in plasma. Since steroid hormone esters circulate for longer periods, we have studied here whether the administration of DHEA oleoyl ester may extend its pharmacologic availability by keeping high circulating levels.ResultsTritium-labelled oleoyl-DHEA was given to Wistar male and female rats by gastric tube. The kinetics of appearance of the label in plasma was unrelated to sex; the pattern being largely coincident with the levels of DHEA-sulfate only in females, and after 2 h undistinguishable from the results obtained using labelled DHEA gavages; in the short term, practically no lipophilic DHEA label was found in plasma. After 24 h only a small fraction of the label remained in the rat organs, with a different sex-related distribution pattern coincident for oleoyl- and free- DHEA gavages. The rapid conversion of oleoyl-DHEA into circulating DHEA-sulfate was investigated using stomach, liver and intestine homogenates; which hydrolysed oleoyl-DHEA optimally near pH 8. Duodenum and ileum contained the highest esterase activities. Pure hog pancreas cholesterol-esterase broke down oleoyl-DHEA at rates similar to those of oleoyl-cholesterol. The intestinal and liver esterases were differently activated by taurocholate and showed different pH-activity patterns than cholesterol esterase, suggesting that oleoyl-DHEA can be hydrolysed by a number of esterases in the lumen (e.g. cholesterol-esterase), in the intestinal wall and the liver.ConclusionThe esterase activities found may condition the pharmacological availability (and depot effect) of orally administered steroid hormone fatty acid esters such as oleoyl-DHEA. The oral administration of oleoyl-DHEA in order to extend DHEA plasma availability has not been proved effective, since the ester is rapidly hydrolysed, probably in the intestine itself, and mainly converted to DHEA-sulfate at least in females.

Low Plasma Dehydroepiandrosterone Sulfate Level and its Relationship to Adiponectin in Hemodialysis Patients

The aim of the present study was to assess the relationship between plasma DHEA-S and adiponectin concentrations in hemodialyses patients (HD). Plasma adiponectin, DHEA-S, cholesterol, and albumin levels were estimated in 94 HD and 46 healthy subjects (HS). In HD, a significantly lower plasma DHEA-S concentration (2.5±0.2 vs. 4.7±0.4 μmol/L respectively; p = 0.002) but significantly higher plasma adiponectin level (15.0±0.7 vs. 8.7±0.8 μg/mL respectively; p = 0.004) than in HS were found. Only in uremic patients was a significant negative correlation found between plasma adiponectin and DHEA-S concentrations (tau = –0.210; p = 0.001). Decreased plasma DHEA-S level is associated with increased adiponectinemia in uremic patients.

Unilateral adrenalectomy improves insulin resistance and polycystic ovaries in a middle-aged woman with virilizing adrenocortical adenoma complicated with Cushing’s syndrome

A benign virilizing adrenal adenoma is rare among adrenal neoplasms in middle-aged women. A 39-yr-old Japanese woman who presented with hirsutism, obesity, diabetes mellitus and hypertension was admitted. Plasma concentrations of testosterone and DHEAS were high. While the basal level of plasma ACTH was suppressed, serum cortisol level was high and its circadian rhythm was absent. Serum cortisol level was not suppressed with the low- and high-dose overnight dexamethasone suppression test. Abdominal computed tomography showed a left adrenal tumor, and an adrenocortical scintigraphy revealed uptake of the tracer on the left side. Polycystic ovaries were also found and bone mineral density revealed osteoporosis. Histopathological features of resected adrenal tumor were consistent with those of adrenocortical adenoma. Immunoreactivity of all the steroidogenic enzymes was apparent in the tumor cells and particularly dehydroepiandrosterone sulfotransferase (DHEA-ST) immunoreactivity was markedly expressed. Cortical atrophy and reduced expression of DHEA-ST were detected in the cortex of the adjacent non-neoplastic adrenal gland. Plasma testosterone, DHEAS and cortisol levels returned to normal after surgery, concomitantly with the disappearance of polycystic ovaries. This is a very rare case of virilizing adrenocortical adenoma complicated with Cushing's syndrome (CS).

An Oxidized Derivative of Linoleic Acid Stimulates Dehydroepiandrosterone Production by Human Adrenal Cells

We previously reported that an oxidized derivative of linoleic acid stimulated steroidogenesis in rat adrenal cells. This derivative was also detected in human plasma, and was positively correlated with visceral adiposity and plasma DHEA-S. The present study sought to characterize the effects of this derivative, 12,13-epoxy-9-keto-(10- trans)-octadecenoic acid (EKODE), on steroid production by normal human adrenocortical cells obtained during clinically-indicated adrenalectomy. Cell suspensions were incubated in the presence of varying concentrations of EKODE and ACTH. EKODE (16 microM) significantly increased DHEA production by 28% under basal conditions and by 25% in the presence of a low concentration of ACTH (0.2 ng/ml). The effect on DHEA was absent at a higher ACTH concentration (2.0 ng/ml). EKODE decreased cortisol production by 16% (low ACTH) and 25% (high ACTH), but was without effect on cortisol under basal conditions. The results suggest that EKODE affects adrenal DHEA production in the human, possibly by modulating steroidogenic enzyme activity. We postulate that excess visceral fat delivers fatty acids to the liver, where oxidized derivatives are formed that modulate adrenal steroidogenesis. This may be an important phenomenon in the genesis of changes in adrenal function associated with syndromes of obesity, especially those that include androgen excess.

Early postoperative changes in testosterone, dehydroepiandrosterone sulfate, and sex hormone-binding globulin after hysterectomy with or without concomitant oophorectomy

To investigate the cross-sectional associations of hysterectomy and oophorectomy status, chronological age, and body mass index with early postoperative plasma levels of total and free T, DHEAS, and sex hormone-binding globulin (SHBG). A cross-sectional study. University hospital. Ninety-two women age 35-47 years who were scheduled for hysterectomy and/or oophorectomy, advocated for benign gynecological pathologies. Ninety-two eligible premenopausal women underwent hysterectomy and/or oophorectomy, with plasma T, DHEAS, and SHBG levels assayed before surgery and during the postoperative period. Effects of time x operation and age x operation interactions between oophorectomized and nonoophorectomized groups and within-subject main effect of time on plasma androgen levels. Of 92 women, hysterectomy alone was performed in only 49 (53.3%) cases. Oophorectomy, either unilateral or bilateral, was performed in 35.8% of cases. Age x within-group interactions exhibited an important difference (P=.03) in total T levels. The time x between- and within-group interaction effects on plasma DHEAS levels of postoperative day 7, compared with day 1, were statistically significant (P<.001). The effect of time x group interaction was remarkable, in terms of SHBG levels during the postoperative period. Age x oophorectomy interaction exhibited a statistically significant change of decline in DHEAS levels on postoperative day 7 (P=.05). The present study demonstrated a time and operation effect decline in plasma DHEAS levels. In contrast, the time x operation interaction on SHBG levels exhibited an increase toward postoperative day 7.

Circulating Progesterone and Obesity in Men

Progesterone can be detected in male plasma and has been considered to originate mainly from the adrenals. We have examined the association between circulating progesterone and obesity in a sample of thirty-eight lean to morbidly obese men aged 44.5 +/- 9.9 years (BMI: 44.3 +/- 12.8 kg/m (2)). Plasma concentrations of progesterone, 17-OH-progesterone as well as androstenedione, testosterone, DHT and DHEA-S were determined. Negative correlations were observed between plasma progesterone levels and body weight (r = - 0.47, p < 0.05), BMI (r = - 0.56, p < 0.001), waist circumference (r = - 0.58, p < 0.001), as well as subcutaneous adipocyte diameter (r = - 0.50, p < 0.05). Plasma levels of 17-OH-progesterone, DHEA-S, androstenedione, testosterone and DHT were also negatively associated with body weight, BMI and waist circumference. However, the ratio of 17-OH-progesterone-to-progesterone and androstenedione-to-17-OH-progesterone were not related to these variables. A positive correlation was found between circulating progesterone and DHEA-S levels (r = 0.50, p < 0.002 after adjustment for age). Accordingly, using multivariate regression analyses, the best steroid predictor of progesterone level was plasma DHEA-S. Waist circumference was the best predictor of progesterone levels in a multivariate model including steroid concentrations as well as waist circumference, BMI and subcutaneous adipocyte diameter. In conclusion, plasma progesterone was negatively associated with markers of obesity such as BMI, waist circumference and subcutaneous adipocyte diameter in this sample of men. Circulating DHEA-S level was the best steroid correlate of plasma progesterone. We suggest that the low progesterone levels observed in obese men may reflect decreased adrenal C(19) steroid production in the adrenal cortex. Further research is needed to confirm this hypothesis.

The Association of Plasma DHEA and DHEA Sulfate with Breast Cancer Risk in Predominantly Premenopausal Women

Concentrations of adrenal androgens are positively associated with postmenopausal breast cancer risk; however, results in premenopausal women are conflicting. Therefore, we conducted a prospective nested case-control study within the Nurses' Health Study II cohort to examine the relationship of DHEA and DHEA sulfate (DHEAS) with breast cancer risk in predominantly premenopausal women. Blood samples were collected from 1996 to 1999. The analysis included 317 cases of breast cancer diagnosed after blood collection and before June 1, 2003; for each case, two controls were matched on age, fasting status, time of day and month of blood collection, race/ethnicity, and timing of blood draw within the menstrual cycle. No associations were observed between DHEA or DHEAS levels and breast cancer risk overall [in situ and invasive; DHEA relative risk (RR), top versus bottom quartile, 1.2; 95% confidence interval (95% CI), 0.8-1.8, P(trend) = 0.53; DHEAS RR, 1.3; 95% CI, 0.9-2.0; P(trend) = 0.07]. However, both DHEA and DHEAS were positively associated with estrogen receptor-positive/progesterone receptor-positive breast cancer (DHEA RR, 1.6; 95% CI, 0.9-2.8, P(trend) = 0.09; DHEAS RR, 1.9; 95% CI, 1.1-3.3, P(trend) = 0.02). We observed a significant interaction by age, with an RR for DHEAS of 0.8 (95% CI, 0.4-1.5, P(trend) = 0.62) for women <45 years old and 2.0 (95% CI, 1.2-3.5, P(trend) = 0.003) for women >/=45 years old; results were similar for DHEA. Our results suggest that adrenal androgens are positively associated with breast cancer among predominately premenopausal women, especially for estrogen receptor-positive/progesterone receptor-positive tumors and among women over age 45 years.

A decrease in the plasma DHEA to cortisol ratio during smoking abstinence predicts relapse

A decrease in the plasma DHEA to cortisol ratio during smoking abstinence predicts relapse Ann M. Rasmusson , Ran Wu , Prashni Paliwal , George M. Anderson , Suchitra Krishnan-Sarin c a Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA b VA National Center for PTSD, Clinical Neuroscience Division, West Haven, CT, USA c Department of Psychiatry and Transdiscipliniary Tobacco Use Research Center, Yale University School of Medicine, New Haven, CT, USA d Department of Psychiatry and Division of Women’s BehavioralHealth, YaleUniversity School ofMedicine, NewHaven, CT, USA e Child Study Center, Department of Laboratory Medicine and Transdisciplinary Tobacco Use Research Center, Yale University School of Medicine, New Haven, CT, USA E-mail address: ann.rasmusson@yale.edu (A.M.Rasmusson)

Pharmacogenetics of human cytosolic sulfotransferases

Cytosolic sulfotransferases (SULTs) are phase II detoxification enzymes that are involved in the biotransformation of a wide variety of structurally diverse endo- and xenobiotics, including many therapeutic agents and endogenous steroids. Single-nucleotide polymorphisms (SNPs) in SULTs have functional consequences on the translated protein. For the most part, these SNPs are fairly uncommon in the population, but some, most notably for SULT isoform 1A1, are commonly found and have been associated with cancer risk for a variety of tumor sites and also with response to therapeutic agents. SNPs in the hydroxysteroid sulfotransferase, SULT2A1, have been identified in African-American subjects and influence the ratio of plasma DHEA:DHEA-S. This modification could potentially influence cancer risk in steroidogenic tissues. SNPs in many SULTs are ethnically distributed, another factor that could influence SULT pharmacogenetics. Finally, genetic variation has also been identified in 3'-phosphoadenoside 5'-phosphosulfate synthetase (PAPPS), the enzymes responsible for producing the obligatory cosubstrate for all sulfotransferases. Taken together, this variability could substantially influence the disposition of drugs metabolized by SULTs. Elucidation of the basis and effect of variability in sulfation could greatly impact individualized therapy in the future.

Impaired reduction of enhanced levels of dehydroepiandrosterone by oral dexamethasone in anorexia nervosa

Allopregnanolone and dehydroepiendrosterone (DHEA) have been supposed to be involved in some psychiatric disorders including anorexia nervosa (AN). The secretion of DHEA and allopregnanolone occurs in both the brain and the adrenal gland, where it is under the control of the corticotrophin-releasing factor (CRF)/adrenocorticotrophin hormone (ACTH) system, and, according to the increased CRF/ACTH drive found in AN, we previously reported enhanced morning levels of both DHEA and allopregnanolone in underweight anorexic patients. To further characterize the physiology of these neurosteroids in AN, we measured plasma levels of cortisol, DHEA and allopregnanolone after the oral administration of 1 mg dexamethasone at 800h in six underweight AN women and ten age-matched healthy females. We found that, before dexamethasone administration, both cortisol and DHEA plasma concentrations were significantly increased in anorexic patients as compared to controls, whereas plasma allopregnanolone levels although increased in the former did not reach a statistical significance. Moreover, while cortisol levels after dexamethasone administration were suppressed in AN to values similar to normal controls, DHEA concentrations, although significantly decreased, remained higher than in normal controls. These data support the view that in AN, the increased production of DHEA may be linked to mechanisms other than the enhanced CRF/ACTH drive.

Impact of Gastric Banding on Plasma Ghrelin, Growth Hormone, Cortisol, DHEA and DHEA-S Levels

Several endocrine abnormalities are reported in obesity. Some are considered as causative factors, whereas others are considered to be secondary effects of obesity. In the current study, we explored the changes in cortisol, growth hormone (GH), DHEA, DHEA-S and GH releasing hormone (ghrelin) plasma levels in morbidly obese subjects who lost abundant weight following laparoscopic adjustable gastric banding (LAGB). 12 morbidly obese adult patients (15 females), age 21-56 years with BMI 46.0+/-4.4 kg/cm(2), were studied. Blood samples were collected before, 6 and 14 months after LAGB. The levels of DHEA, DHEA-S, cortisol, GH, and ghrelin were determined by commercial kits. Statistical analysis was based on one-way repeated measures ANOVA, followed by Student-Newman-Keuls post-hoc test. Mean BMI reduced significantly along the study course (P=.000). Cortisol plasma levels significantly decreased 6 months after surgery (from 541.4+/-242.4 nM to 382.4+/-142.1 nM, P=.004), but did not change further after 14 months (460.2+/-244.9 nM), despite further reduction in BMI (P=.050). GH constantly increased throughout the study from 0.076+/-0.149 ng/ml, to 0.410+/-0.509 ng/ml at 6 months (NS), to 1.224+/-1.738 ng/ml at 14 months after surgery (P=.001). DHEA, DHEA-S and ghrelin plasma levels remained stable throughout the study. GH levels showed a persistent increase during the 14 months following LAGB in association with the weight loss, while a transient decrease in cortisol levels occurred at the 6-months time-point. In contrast, ghrelin, DHEA and DHEA-S were not altered after surgery. The association between GH and cortisol secretion and surgical- and nonsurgical-induced weight reduction merits further investigation.

Administration of prenatal betamethasone suppresses the adrenal–hypophyseal axis in newborns with congenital diaphragmatic hernia

Background Congenital diaphragmatic hernia (CDH) is a condition that is characterized by pulmonary hypoplasia and pulmonary hypertension. Prenatal betamethasone often is administered to fetuses with CDH to improve pulmonary function. In this study, the authors investigate the possible role of the adrenal-hypophyseal axis in CDH in an animal model and subsequently in human infants with CDH. Methods Twin fetal sheep underwent creation of DH or a sham thoracotomy, and levels of plasma and lung ACTH and plasma cortisol were compared. For the human studies, plasma levels of ACTH, cortisol, and DHEA were measured in cord blood samples collected from 9 CDH (5 that received prenatal betamethasone) and compared with those of 14 normal newborns. In both studies, ACTH and cortisol levels were determined by radioimmunoassay (RIA). Human (DHEA) levels were determined by ELISA. Results Plasma ACTH and cortisol levels were elevated in fetal DH sheep compared with sham-operated controls; however, levels of ACTH in lung tissues were not different. Human newborns with CDH who have been exposed to prenatal steroids have significantly lower plasma ACTH, cortisol, and DHEA levels than normal newborns and CDH newborns not exposed to prenatal betamethasone. Conclusions In an ovine model of CDH, the adrenal-hypophyseal axis appears up-regulated in DH fetuses compared with sham-operated animals. Conversely, the adrenal-hypophyseal axis in human CDH newborns appears normal but is suppressed by the administration of prenatal betamethasone.

Plasma Adrenal Androgens and Risk of Breast Cancer in Premenopausal Women

Abstract Objectives: Plasma DHEA and its sulfate (DHEA-S) are positively associated with breast cancer risk in postmenopausal women; but the relationships have not been studied in detail in premenopausal women. We prospectively evaluated relationships between plasma levels of DHEA and DHEA-S in blood samples provided by a group of primarily premenopausal women and subsequent breast cancer, by use of case-control sampling from the Nurses' Health Study cohort. Method: Blood samples were collected from 1989 to 1990. Among women who were not postmenopausal at blood collection, 302 were diagnosed with breast cancer between blood collection and June 1998. Two controls were selected per case and matched with respect to age, menopausal status, month and time of day of blood collection, and fasting status at blood collection. Statistical analyses using conditional logistic regression were done to adjust for potential confounders. Results: At time of blood collection, the median age was 49 (10th to 90th percentiles 45 to 53). In multivariable analyses, the highest quartile of DHEA was associated with an odds ratio of breast cancer of 0.92 (95% confidence interval, 0.59-1.43) relative to the lowest quartile (P value for log-linear trend 0.11). A similar analysis revealed an odds ratio of 1.08 (0.69-1.69) for DHEA-S (P value for log-linear trend 0.83). No statistically significant interactions were noted according to certainty of menopausal status, age, or past oral contraceptive use. Discussion: Our analysis did not reveal a relationship between DHEA or DHEA-S and subsequent breast cancer in middle-aged premenopausal women. In the future, this relationship should be studied in younger women.

Long-term low-dose dehydroepiandrosterone oral supplementation in early and late postmenopausal women modulates endocrine parameters and synthesis of neuroactive steroids

Objective To evaluate the effects of a low-dose DHEA supplementation on hormonal parameters in early and late postmenopausal women. Design Prospective case study. Setting Postmenopausal women in a clinical research environment. Patient(s) Twenty postmenopausal women were divided in two groups according to age (50–55 and 60–65 years). Intervention(s) All patients underwent hormonal evaluation before and at 3, 6, 9, and 12 months of therapy (25 mg/d of DHEA orally). Pelvic ultrasound examination and Kupperman score were performed before and after 3, 6, and 12 months of therapy. Main outcome measure(s) Plasma DHEA, DHEAS, estrone (E 1), E 2, P, androstenedione (A), T, dihydrotestosterone, 17α-hydroxyprogesterone (17-OHP), cortisol (F), allopregnanolone, β-endorphin, sexual hormone-binding globulin (SHBG), LH, FSH, growth hormone (GH), and insulin-like growth factor-1 (IGF-1) concentrations. Results The levels of all the steroids that derive from DHEA metabolism increased in plasma with DHEA administration. Also neurosteroids (namely allopregnanolone) and endorphin showed increased plasma levels, whereas both gonadotropins were significantly reduced. Endometrial thickness did not change throughout the study period. Conclusions Administration of low doses (25 mg) of DHEA positively modulates several endocrine parameters in early and late postmenopausal women, inducing the increase of the androgenic, estrogenic, and progestogenic milieu and reducing the climateric symptoms, similarly to estroprogestin replacement therapy. These data suggest that DHEA supplementation is a more effective replacement therapy than a simple “dietary supplement.”

Basal endocrine status in African dietary iron overload.

Endocrine disturbances, notably diabetes, have been well described as a complication of iron overload due to hereditary hemochromatosis and beta-thalassemia. Dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis has also been well documented. The pattern of iron loading in African iron overload with saturated transferrin is similar to that seen in hereditary hemochromatosis. In addition, many symptoms ascribed to pituitary dysfunction are common to both conditions. The present study was undertaken to assess whether a similar pattern of endocrine dysfunction occurs in African iron overload. Thirty subjects with African iron overload and transferrin saturation >50%, plus 30 age and sex matched normal controls were studied. An iron profile, fasting plasma glucose, cortisol, DHEA-S, LH, FSH, growth hormone, prolactin, TSH, and FT4 levels were measured in all 60 subjects as well as testosterone in the males and estradiol in the females. Iron loading in the subjects with increased transferrin saturation ranged from moderate to severe. No significant differences were found in the mean testosterone, estradiol, LH, DHEA-S, growth hormone, prolactin, or TSH levels between the subjects and normal controls. In female subjects, although within the normal range, the mean FSH level was significantly higher, probably due to their being somewhat older and in a more advanced stage of menopause than the control females. Mean cortisol concentrations were increased in both genders in the patient group, significantly so in the females; however, values were within the reference range. We conclude therefore that there appears to be no major impairment of endocrine function in the basal state in African iron overload subjects with moderate to severe degrees of iron loading.

Hyperinsulinemia and uterine perfusion in patients with polycystic ovary syndrome.

To determine whether hyperinsulinemia has a negative effect on uterine blood supply in patients with polycystic ovary syndrome (PCOS). Sixty-three patients with normal body mass index were included prospectively in the study: 48 had clinical and hormonal features of PCOS and 15 were normo-ovulatory. All patients underwent Doppler flow measurement of the uterine artery, and determination of serum concentrations of luteinizing hormone, follicle stimulating hormone, prolactin, estradiol, androgens, insulin and C-peptide during the early follicular phase of the menstrual cycle. The 48 PCOS-patients were divided into two groups according to the pulsatility index (PI) value of the uterine artery: Group 1, PI < 3; Group 2, PI >or= 3 and the groups were compared. The mean PI of the uterine artery (3.01 +/- 1.0 vs. 1.93 +/- 0.3, respectively) and fasting levels of insulin (50.9 +/- 9.3 vs. 40.3 +/- 10.9) and C-peptide (366.9 +/- 118.4 vs. 243.6 +/- 120.3) of PCOS-patients were significantly higher than those of the control group. No correlation was found between insulinemia and C-peptide and PI of the uterine artery and no significant difference was found in insulin and C-peptide levels among the two groups of PCOS-affected patients. Only the serum level of dehydroepiandrosterone sulfate was significantly higher in Group 2, and a direct correlation was found between PI values of the uterine artery and DHEAS plasma levels. Insulin and C-peptide do not seem to interfere with uterine perfusion in PCOS-affected patients.

Elevated Blood Levels of Dehydroepiandrosterone Sulphate Vary with Symptom Load in Posttraumatic Stress Disorder: Findings from a Longitudinal Study of Refugees in Sweden

Background: The present study is part of a longitudinal study of recently resettled refugees with the aim of learning which factors in their daily life influence health as measured by self-report and stress-responsive hormones. Methods: In a group of recently resettled refugees with a high incidence of posttraumatic stress disorder (PTSD), diagnosed by structured interview, self-rated symptoms of PTSD were followed three times over a period of 9 months after inclusion in the study. Eighty-six individuals were included in the study and 58 subjects (67.4%) completed it. Blood samples were drawn at each examination for assessment of hormone levels. Results: After adjustment for age, dehydroepiandrosterone sulphate (DHEA-s) was observed to be higher in non-depressed PTSD cases than in non-PTSD without depression. There was an interaction between PTSD and depression regarding DHEA-s levels. DHEA-s correlated significantly with changes in self-rated symptoms of PTSD at last follow-up; the greater the increase in PTSD symptoms, the greater the increase in plasma DHEA-s. The variation of DHEA-s levels in relation to changes in self-rated health in non-PTSD showed the opposite pattern, although not reaching significance. Conclusions: The finding of changes in DHEA-s should encourage further studies of the role of altered steroid metabolism in PTSD.

Involvement of the hypothalamic-pituitary-adrenal axis in children with oligoarticular-onset idiopathic arthritis.

Adult patients with rheumatic arthritis and other rheumatic disorders show inappropriate cortisol secretion and peculiar CRH promoter gene polymorphisms. So far, no data are available about this topic in children with juvenile idiopathic arthritis (JIA). We have studied a series of 13 prepubertal patients (10 female, 3 male) affected with oligoarticular JIA (o-JIA) without clinical and biological signs of disease activity (ESR and IL-6). ACTH plasma concentrations were significantly increased at 8 a.m. in o-JIA patients, whereas no differences were found in cortisol plasma concentrations. The ACTH/cortisol ratio was significantly increased in o-JIA patients with respect to the normal population both at 8 a.m. and at noon. DHEAS and testosterone plasma concentration did not statistically differ in the two populations. The genetic study was aimed at defining the prevalence of polymorphisms A1 and A2 in o-JIA patients, but we failed to find allelic or genotypic differences. Our study suggests the presence of a partial resistance to ACTH with a dysregulated pattern of secretion also in inactive o-JIA patients. These preliminary data need further confirmation in larger pediatric studies.

Specific radioimmunoassay of estrone sulfate: Application to measurement in male plasma

We described a new, specific and easy to use radioimmunoassay (RIA) of estrone sulfate (E1S) in males. After synthesis of an E1S-6-( O-carboxymethyl) oxime hapten then coupling to BSA, we obtained a specific anti-E1S antiserum. Although the cross-reactivity of DHEAS with our anti-E1S antiserum was low (CR=0.002%), we confirmed the absolute necessity of separating plasma DHEAS from plasma E1S, before E1S RIA, because in plasma, DHEAS is present at levels 3–6000-fold higher than E1S, which generally is ignored. Thus, we elicited an easy separation of DHEAS from E1S, by a fast chromatography on in-house minicolumns. This new RIA, was applied to the determination of E1S plasma normal values in males. In 27 young men (<35 years), mean±S.D. were 1.97 nmol/l±1.07 nmol/l and in 63 untreated healthy aged men (>55 years), 1.80 nmol/l±1.21 nmol/l . No significant difference was seen between young and older subjects. The ranges of E1S plasma levels in these subjects were rather large and the ratios between the highest and the lowest E1S plasma levels were seven in the young group and 23.4 in the older group. No decrease of E1S plasma levels was observed with ages. Contrary to large interindividual E1S plasma level variations, the intraindividual variations have been found to be no significant. Correlations between E1S and unconjugated estrogens, E2 and E1 were 0.22 ( P=0.016) and 0.51 (0.001), respectively.