Serum Dehydroepiandrosterone Sulfate Concentrations Research Articles

Circulating concentration of dehydroepiandrosterone sulfate (DHEA-S) in women suffering from chronic idiopathic urticaria in relation to their pre- or post-menopausal status

ObjectiveAs chronic urticaria in pre-menopausal women was accompanied by lower serum concentration of DHEA-S and because it had been known that endocrine profiles changed along with ageing, in the present study we investigated DHEA-S behaviour in post-menopausal women suffering from chronic idiopathic urticaria (CIU). MethodsSerum concentration of DHEA-S was measured in 32 post-menopausal women, aged between 49 and 66, suffering from CIU, as well as in 30 healthy subjects matched for age, body mass index, and years since menopause. ResultsNo statistical difference in DHEA-S serum concentration was found between the CIU patients and the controls (median 99.63ug/dl versus 108.25ug/dl, respectively). ConclusionsThe observations made recently and those of our previous results may point to the existence of two different hormonal patterns of DHEA-S circulating concentration in female patients suffering from CIU, depending on age of the disease onset. The scope of the study has been limited however, due to the small number of subjects.

Relationship between low serum endogenous androgen concentrations and arterial stiffness in men with type 2 diabetes mellitus

The aim of this study was to evaluate the relationship between arterial stiffness determined by pulse wave velocity (PWV) and serum endogenous androgen concentrations as well as major cardiovascular risk factors in men with type 2 diabetes mellitus. Serum free testosterone and dehydroepiandrosterone sulfate (DHEA-S) concentrations were measured in 268 men with type 2 diabetes mellitus. Relationships between PWV and serum endogenous androgen concentrations as well as major cardiovascular risk factors, including age, blood pressure, serum lipid concentration, glycemic control (hemoglobin A 1c), body mass index, and degree of albuminuria, were evaluated. Positive correlations were found between PWV and age ( r = 0.491, P < .0001), duration of diabetes ( r = 0.320, P < .0001), systolic blood pressure ( r = 0.292, P < .0001), and log (urinary albumin excretion) ( r = 0.269, P < .0001). Inverse correlations were found between serum free testosterone concentration and PWV ( r = −0.228, P = .0003) and between serum DHEA-S concentration and PWV ( r = −0.252, P = .0002) in men with type 2 diabetes mellitus. Pulse wave velocity was significantly greater in patients with lower concentrations of free testosterone (<10 pg/mL) than in patients with higher concentrations of free testosterone (1864 ± 359 vs 1736 ± 327 cm/s; P = .0053). Pulse wave velocity also was significantly greater in patients with lower concentrations of DHEA-S (<1000 ng/mL) than in patients with higher concentrations of DHEA-S (1843 ± 371 vs 1686 ± 298 cm/s; P = .0008). Multiple regression analysis identified both serum free testosterone concentration ( β = −.151, P = .0150) and serum DHEA-S concentration ( β = −.200, P = .0017) as independent determinants of PWV. In conclusion, serum endogenous androgen concentrations are inversely associated with arterial stiffness determined by PWV in men with type 2 diabetes mellitus, which is true for men in general based on other works.

Impact of CYP3A7*1C polymorphism on bone mineral content in postmenopausal women

CYP3A7*1C polymorphism has been shown to be associated with lower levels of serum dehydroepiandrosterone sulphate in men. The age-related decline of dehydroepiandrosterone sulphate levels is believed to contribute to the development of osteoporosis. We hypothesized that CYP3A7*1C may lead to bone loss through decreased levels of dehydroepiandrosterone sulphate in postmenopausal women. 319 postmenopausal women were studied and divided into two subgroups: 217 women with osteoporosis and 102 aged-matched women without osteoporosis. The CYP3A7*1C polymorphism was genotyped. Serum dehydroepiandrosterone sulphate levels and bone mineral density were measured. Homozygous CYP3A7*1C carriers had significantly lower bone mineral density at lumbar spine than that of wild type (T-score with CYP3A7*1C mutant type: -3.27 +/- 1.02, T-score with wild type: -1.35 +/- 1.53, p = 0.041) after adjusting for age and DHEAS levels. No association was found between genotypes and dehydroepiandrosterone sulphate levels. Our data suggest that CYP3A7 polymorphism might have an influence on bone mass at the lumbar spine independently of serum dehydroepiandrosterone sulphate concentrations.

Metabolic syndrome is not associated with markers of subclinical atherosclerosis, serum adiponectin and endogenous androgen concentrations in Japanese men with Type 2 diabetes

Metabolic syndrome is characterized by its association with certain cardiovascular disease risk factors. The aim of this study was to investigate the relationships between metabolic syndrome and markers of subclinical atherosclerosis, serum adiponectin and endogenous androgen concentrations in Japanese men with Type 2 diabetes. Using the 2005 International Diabetes Federation (IDF) definition, we assessed the prevalence of the metabolic syndrome in 424 consecutive men with Type 2 diabetes aged 40-75 years in a cross-sectional study. We compared characteristics including ultrasonographic carotid atherosclerosis markers, pulse-wave velocity (PWV), and serum adiponectin, free testosterone, and dehydroepiandrosterone sulphate (DHEA-S) concentrations in diabetic patients with and without the metabolic syndrome. The prevalence of the metabolic syndrome in Japanese men with Type 2 diabetes was 46.9%. Men with the metabolic syndrome had higher urinary albumin excretion rate than those without. Carotid intima-media thickness (0.97 +/- 0.26 vs. 0.91 +/- 0.18 mm), plaque score [3.3 (1.5-8.1) vs. 3.8 (1.3-6.2)], PWV (1818 +/- 331 vs. 1749 +/- 331 cm/s) and ankle-brachial index (1.10 +/- 0.14 vs. 1.08 +/- 0.16) did not differ significantly between patients with and without the metabolic syndrome. Similarly, serum adiponectin [3.70 (2.06-6.09) vs. 4.65 (3.09-7.02) microg/ml], free testosterone (36.4 +/- 10.7 vs. 34.7 +/- 11.1 pmol/l), and DHEA-S concentrations (3.29 +/- 1.83 vs. 3.17 +/- 1.63 micromol/l) did not differ significantly between groups, The metabolic syndrome, as defined by the IDF, is not significantly associated with subclinical atherosclerosis markers, serum adiponectin, or endogenous androgen concentrations in Japanese men with Type 2 diabetes.

Association Between Urinary Albumin Excretion and Serum Dehydroepiandrosterone Sulfate Concentrations in Women With Type 2 Diabetes

Both elevated urinary albumin excretion (UAE) and low serum concentrations of dehydroepiandrosterone (DHEA) have been linked with increased cardiovascular disease (CVD) mortality in men (1–5). We have recently demonstrated that serum DHEA sulfate (DHEA-S) concentrations correlated inversely with degree of UAE in men with type 2 diabetes (6). However, findings supporting a protective role of DHEA for CVD have been inconsistent in women (7–9). Furthermore, to our knowledge, the relationship between serum DHEA-S concentrations and degree of UAE, a marker of CVD, has never been explored in women with type 2 diabetes. We therefore investigated the relationship between serum DHEA-S concentrations and degree of UAE, as well as pulse wave velocity (PWV), a marker of arterial stiffness, in women with type 2 diabetes. Relationships of UAE to serum DHEA-S concentrations and to major cardiovascular risk factors were investigated in 254 consecutive women with type 2 diabetes who were recruited from the outpatient clinic at the Kyoto Prefectural University of Medicine. Most patients were postmenopausal women ( n = 244), and no patients received hormone replacement therapy. Mean values for BMI, blood pressure, and biochemical parameters obtained during the preceding year were used for statistical analysis. Patients enrolled in this study were almost stable for control of diabetes, hypertension, and dyslipidemia, …

CYP3A7*1C Polymorphism, Serum Dehydroepiandrosterone Sulfate Level, and Bone Mineral Density in Postmenopausal Women

The CYP3A7 enzyme metabolizes some steroid hormones, including dehydroepiandrosterone sulfate (DHEAS). The age-related decline of serum DHEAS levels is believed to contribute to osteoporosis. Previously, the CYP3A7*1C polymorphism has been shown to cause a persistent high CYP3A7 enzyme activity, resulting in lower levels of DHEAS in men. We hypothesized that the CYP3A7*1C polymorphism might contribute to bone loss through decreased levels of serum DHEAS in postmenopausal women. Postmenopausal women (n = 319) were divided into two subgroups: 217 with osteoporosis and 102 healthy controls. Genotyping, serum DHEAS measurement, and osteodensitometry of the lumbar spine and femoral neck were carried out in all subjects. Homozygous CYP3A7*1C carriers had significantly lower BMD at the lumbar spine compared to wild types (T score -3.27 +/- 1.02 in CYP3A7*1C homozygous mutants vs. -1.35 +/- 1.53 in wild types, P = 0.041). This association remained significant after adjustment for menopausal age, serum DHEAS level, alcohol consumption, steroid intake, smoking habits, and previous fractures. No association was found between genotypes and serum DHEAS levels in the total study population or in the subgroups. Serum DHEAS levels correlated positively with bone mineral density at the lumbar spine (r = 0.59, P = 0.042) after correction for age. Our data suggest that the CYP3A7 polymorphism might have an influence on bone mass at the lumbar spine independently of serum DHEAS concentrations.

Role of Endogenous Androgen Against Insulin Resistance and Athero-sclerosis in Men with Type 2 Diabetes

Age-related decline in serum testosterone and dehydroepiandrosterone sulfate concentrations occur in men. Low concentrations of these endogenous androgens have been linked with insulin resistance, which is an important upstream driver for metabolic abnormalities such as hyperglycemia, hypertension, or hyperlipidemia, and increased cardiovascular risk. Moreover, men with diabetes have significantly less circulating androgen than nondiabetic men. Here, we summarize how androgen affects insulin resistance and atherosclerosis in men with type 2 diabetes. Low serum concentrations of endogenous androgens are associated with visceral fat accumulation. Androgen deprivation by castration to treat prostate cancer increases insulin resistance, while testosterone administration in type 2 diabetic men with androgen deficiency improves glucose homeostasis and decreases visceral fat, in addition to alleviating symptoms of androgen deficiency including erectile dysfunction. Androgen correlates inversely with severity of atherosclerosis and has beneficial effects upon vascular reactivity, inflammatory cytokine, adhesion molecules, insulin resistance, serum lipids, and hemostatic factors. Because men with type 2 diabetes have relative hypogonadism, testosterone supplementation could decrease both insulin resistance and atherosclerosis.

Effects of melatonin administration on the clinical course of adrenocortical disease in domestic ferrets

To evaluate the effect of oral administration of melatonin on clinical signs, tumor size, and serum steroid hormone concentrations in ferrets with adrenocortical disease. Noncontrolled clinical trial. 10 adult ferrets with clinical signs of adrenocortical disease (confirmed via serum steroid hormone concentration assessments). Melatonin (0.5 mg) was administered orally to ferrets once daily for 1 year. At 4-month intervals, a complete physical examination; abdominal ultrasonographic examination (including adrenal gland measurement); CBC; serum biochemical analyses; and assessment of serum estradiol, androstenedione, and 17alpha-hydroxyprogesterone concentrations were performed. Serum prolactin and dehydroepiandrosterone sulfate concentrations were evaluated at the first, second, and last examinations, and serum cortisol concentration was evaluated at the first and last examinations. Daily oral administration of melatonin greatly affected clinical signs of adrenocortical disease in ferrets; changes included hair regrowth, decreased pruritus, increased activity level and appetite, and decreased vulva or prostate size. Mean width of the abnormally large adrenal glands was significantly increased after the 12-month treatment period. Recurrence of clinical signs was detected in 6 ferrets at the 8-month evaluation. Compared with pretreatment values, serum 17alpha-hydroxyprogesterone and prolactin concentrations were significantly increased and decreased after 12 months, respectively. Results suggest that melatonin is a useful, easily administered, palliative treatment to decrease clinical signs associated with adrenocortical disease in ferrets, and positive effects of daily treatment were evident for at least an 8-month period. Oral administration of melatonin did not decrease adrenal gland tumor growth in treated ferrets.

Positive correlation between anxiety severity and plasma levels of dehydroepiandrosterone sulfate in medication‐free patients experiencing a major episode of depression

Although numerous studies have identified a correlation between dehydroepiandrosterone sulfate (DHEAS) levels and anxiety or depression, those findings remain controversial. The purpose of the present study was to determine whether a correlation exists between depression severity and anxiety severity and serum DHEAS concentrations in medication-free patients experiencing a major depressive episode. Twenty-eight medication-free major depressive outpatients (Hamilton Rating Scale for Depression 17 [HAM-D 17] score >or=17) were enrolled consecutively. Plasma DHEAS levels of all subjects were measured. Blood from subjects was drawn at 0900-1100 h Depression severity was assessed with the HAM-D 17 and the Hospital Anxiety and Depression Scale (HADS) depression subscale. Anxiety was assessed using the HADS anxiety subscale. Serum concentrations of DHEAS were measured immediately following the HAM-D 17 and HADS assessments. A significant, positive correlation was identified between HADS anxiety subscale total score and morning serum DHEAS concentration (P = 0.013) after controlling for age, gender and body mass index (BMI). No statistically significant correlations were found between depression ratings and morning serum DHEAS concentrations. This preliminary study provides pilot data indicating that morning serum DHEAS concentrations were positively correlated with HADS anxiety subscale score (anxiety severity) after controlling for age, gender and BMI in medication-free outpatients experiencing a major depressive episode. It is not known if morning serum DHEAS levels would show similar or dissimilar changes in non-depressed subjects. The present result needs subsequent replication.

Serum concentrations of dehydroepiandrosterone sulfate (DHEA-S) in oldest old Japanese women correlate with cognitive activity rather than activities of daily living

Background: Dehydroepiandrosterone (DHEA) and its interconvertible sulfate ester, DHEA sulfate (DHEA-S), mainly produced by the adrenal glands, are progressively decreased with aging and are proven markers of longevity. Although serum level of DHEA (-S) has been shown to be decreased in dementing diseases, the issue remains controversial. We investigated the physiological significance of DHEA-S in oldest old Japanese women in respect of activities of daily living (ADL) or cognitive activities. Methods: Cross-sectional study of 50 women aged 90–103 years old. Serum concentrations of DHEA-S levels were measured by radioimmunoassay. ADL and cognitive activity were evaluated by the Bathel index and revised Hasegawa’s dementia rating scale (HDS-R), respectively. Univariate or multivariate regression analyzes were used for statistics. Results: Of the 50 subjects, 80% exceeded the lowest level of the normal range for women in their forties. Serum concentrations of DHEA-S were significantly correlated with HDS-R but not with the Barthel index. Conclusion: Relatively higher levels of serum DHEA-S in oldest old women may reflect the longevity of this population and the levels might be associated with cognitive activity rather than ADL.

Effect of resistance exercise on dehydroepiandrosterone sulfate concentrations during a 72-h recovery: Relation to glucose tolerance and insulin response

Serum dehydroepiandrosterone sulfate (DHEA-S) concentration is known to be associated with the whole-body insulin sensitivity. The main purpose of the study was to investigate the effect of resistance exercise on DHEA-S concentration during a 72 h post-exercise recovery, and its relation to glucose tolerance and insulin sensitivity. Morning fasted serum samples was obtained from 19 male volunteers (aged 21.1 ± 0.4 years) 24 h before the onset of exercise and 24 h, 48 h, and 72 h following exercise for measurements of DHEA-S, cortisol, and TNF-α. Oral glucose tolerance test (OGTT) and insulin response were determined 24 h before and 48 h after exercise. We found that resistance exercise causes a delayed suppression in serum DHEA-S levels during recovery (48 h and 72 h). This exercise challenge did not affect glucose tolerance, but insulin response during OGTT was significantly elevated. The increased insulin level was not associated with serum levels of cortisol and TNF-α. In conclusion, the present study found that resistance exercise has a DHEA-S lowering effect that persisted for 72 h. This change could be related to the elevated insulin concentrations during OGTT.

Effect of Resistance Exercise on Dehydroepiandrosterone Sulfate Concentration During Recovery

Serum dehydroepiandrosterone sulfate (DHEA-S) concentration is known to associate with the whole-body insulin sensitivity. Few information regarding the effect of resistance exercise on DHEA-S level and its relation to glucose tolerance. PURPOSE: To investigate the effect of resistance exercise on DHEA-S concentration during a 72-h postexercise recovery, and its relation to glucose tolerance and insulin sensitivity. METHODS: Serum samples was obtained from 19 male volunteers (aged 21. 2 ± 0.4 years) 24 h before the onset of exercise and 24 h, 48 h, and 72 h following exercise for measurements of DHEA-S, cortisol, and TNF-?. Oral glucose tolerance test (OGTT) and insulin response were determined 24 h before and 48 h after exercise. RESULTS: Significant delayed suppression in serum DHEA-S levels during recovery (48 h and 72 h) was caused by resistance exercise. The exercise did not affect glucose tolerance, but insulin response during OGTT was significantly elevated. The increased insulin level was not associated with serum levels of cortisol and TNF-?. CONCLUSION: The present study found that resistance exercise has a DHEA-S lowering effect persisted for 72 h. This change appears to be related to the elevated insulin concentrations during OGTT.

Low serum dehydroepiandrosterone sulfate concentration is a predictor for deterioration of urinary albumin excretion in male patients with type 2 diabetes

We recently found that serum dehydroepiandrosterone sulfate (DHEA-S) concentration correlated inversely with the degree of urinary albumin excretion in a cross-sectional study. We therefore performed an observational study to investigate the relationship between serum DHEA-S concentrations and changes in urinary albumin excretion in male patients with type 2 diabetes to answer the question as to whether DHEA is a causal rather than simply coincidental intermediate linking urinary albumin excretion to cardiovascular disease (CVD). The relationship between serum DHEA-S concentration and changes in urinary albumin excretion was investigated in 207 consecutive male patients with type 2 diabetes. Baseline serum DHEA-S concentration and urinary albumin excretion were measured in 2003. After 12 months, urinary albumin excretion was measured and any changes in urinary albumin excretion were calculated. Patients were divided into tertiles according to DHEA-S concentration. Greater changes in urinary albumin excretion were seen in patients with low DHEA-S concentration (29.6 ± 7.6 mg/g creatinine) than in patients with high DHEA-S concentration (5.1 ± 3.6 mg/g creatinine, P = 0.0091). An inverse correlation was observed between serum DHEA-S concentration and changes in urinary albumin excretion ( r = −0.193, P = 0.0052). Multiple regression analysis demonstrated that HbA1c ( β = 0.241, P = 0.0009), and serum DHEA-S concentration ( β = −0.195, P = 0.0054) were independent determinants of changes in urinary albumin excretion. In conclusion, serum DHEA-S concentration was inversely correlated with changes in urinary albumin excretion, which may indicate causality in the increased CVD mortality in male patients with type 2 diabetes and low DHEA-S concentration.

Fat Intake Is Associated with Serum Estrogen and Androgen Concentrations in Postmenopausal Japanese Women

A reduction in fat intake has been associated with decreased estrogen levels in dietary intervention studies. However, previous cross-sectional studies conducted mainly among Western populations did not find a positive association between fat intake and postmenopausal estrogen levels. This study examined the cross-sectional association of fat intake with serum levels of estrone, estradiol, testosterone, and dehydroepiandrosterone sulfate (DHEAS) in women. Study subjects were 324 healthy postmenopausal Japanese women. Diet including fat intake was assessed by a validated semiquantitative FFQ. After controlling for age and other potential breast cancer risk factors, serum estrone was positively associated with the percentage of energy from total fat (P = 0.04). The associations of serum estrone with monounsaturated fat and polyunsaturated fat were of borderline significance (P = 0.05). Serum DHEAS was positively associated with the percentage of energy from total fat (P = 0.007), saturated fat (P = 0.009), monounsaturated fat (P = 0.006), and polyunsaturated fat (P = 0.04). Serum estrone and DHEAS concentrations increased 11.8 and 9.3%, respectively, with a 5% increase in the percentage of energy from total fat. These data suggest that a high intake of fat is associated with higher serum levels of estrone and DHEAS in postmenopausal women.

Association between alcohol consumption and serum dehydroepiandrosterone sulphate concentration in men with Type 2 diabetes: a link to decreased cardiovascular risk

Cardiovascular disease (CVD) is the leading cause of mortality and morbidity in patients with Type 2 diabetes. Both light-to-moderate alcohol consumption and higher serum concentrations of dehydroepiandrosterone (DHEA) are associated with reduced CVD mortality, raising the possibility of DHEA as a causal intermediate in CVD and alcohol consumption. Relationships between alcohol consumption and serum DHEA sulphate (DHEA-S) concentration, carotid atherosclerosis as evaluated by carotid ultrasonography and major cardiovascular risk factors were investigated in 404 consecutive men with Type 2 diabetes. Patients were divided into three groups according to mean ethanol consumption per week: non-drinkers, light-to-moderate drinkers (< 210 g per week) or heavy drinkers (> or = 210 g per week). Plasma HDL-cholesterol was positively associated with the degree of alcohol consumption. Intima-media thickness (0.92 +/- 0.21 vs. 1.09 +/- 0.35 mm, P < 0.0001) and plaque score (3.0 +/- 3.3 vs. 5.2 +/- 4.9, P = 0.008) were lower in light-to-moderate drinkers than in non-drinkers. Serum DHEA-S concentrations were higher in light-to-moderate drinkers (1264.2 +/- 592.2 ng/ml, P < 0.0001) and heavy drinkers (1176.2 +/- 607.6 ng/ml, P = 0.0100) than in non-drinkers (956.8 +/- 538.6 ng/ml). In a subgroup aged 60-75-year-old patients (n = 277), serum DHEA-S concentrations were higher in light-to-moderate drinkers (1126.8 +/- 502.5 ng/ml, P = 0.0121) than in non-drinkers (937.9 +/- 505.1 ng/ml). Also, in a subgroup without CVD (n = 339), serum DHEA-S concentrations were higher in light-to-moderate drinkers (1328.5 +/- 593.7 ng/ml, P < 0.0001) than in non-drinkers (970.1 +/- 540.7 ng/ml). Higher serum DHEA-S concentrations in light-to-moderate drinkers may represent part of the link between light-to-moderate alcohol consumption and lower CVD mortality.

Estrogenic Effect of Yam Ingestion in Healthy Postmenopausal Women

Objective: Yam (Dioscorea) has been used to treat menopausal symptom folklorically. This study was to investigate the effects of yam ingestion on lipids, antioxidant status, and sex hormones in postmenopausal women.Methods: Twenty-four apparently healthy postmenopausal women were recruited to replace their staple food (rice for the most part) with 390 g of yam (Dioscorea alata) in 2 of 3 meals per day for 30 days and 22 completed the study. Fasting blood and first morning urine samples were collected before and after yam intervention for the analyses of blood lipids, sex hormones, urinary estrogen metabolites and oxidant stress biomarker. The design was a one arm, pre-post study. A similar study of postmenopausal women (n = 19) fed 240 g of sweet potato for 41 days was included as a control study. Serum levels of estrone, estradiol and SHBG were analyzed for this control group.Results: After yam ingestion, there were significant increases in serum concentrations of estrone (26%), sex hormone binding globulin (SHBG) (9.5%), and near significant increase in estradiol (27%). No significant changes were observed in serum concentrations of dehydroepiandrosterone sulfate, androstenedione, testosterone, follicular stimulating hormone, and luteinizing hormone. Free androgen index estimated from the ratio of serum concentrations of total testosterone to SHBG decreased. Urinary concentrations of the genotoxic metabolite of estrogen, 16α-hydroxyestrone decreased significantly by 37%. Plasma cholesterol concentration decreased significantly by 5.9%. Lag time of low-density lipoprotein oxidation prolonged significantly by 5.8% and urinary isoprostane levels decreased significantly by 42%. For the control subjects fed with sweet potato, all three hormone parameters measured were not changed after intervention.Conclusion: Although the exact mechanism is not clear, replacing two thirds of staple food with yam for 30 days improves the status of sex hormones, lipids, and antioxidants. These effects might reduce the risk of breast cancer and cardiovascular diseases in postmenopausal women.

Serum dehydroepiandrosterone sulfate concentration and carotid atherosclerosis in men with type 2 diabetes

Decreased serum dehydroepiandrosterone (DHEA) concentrations may be associated with an increased risk of cardiovascular disease (CVD) in men. We evaluated relationships between serum DHEA sulfate (DHEA-S) concentration and carotid atherosclerosis, as well as major cardiovascular risk factors, in men with type 2 diabetes. Serum DHEA-S concentrations were measured in 206 consecutive men with type 2 diabetes. Relationships were analyzed between serum DHEA-S concentration and carotid atherosclerosis, determined by ultrasonographically evaluated intima–media thickness (IMT) and plaque score (PS), as well as major cardiovascular risk factors, including age, blood pressure, and lipid concentrations. Negative correlations were found between DHEA-S concentration and IMT ( r = −0.298, P < 0.0001) and between DHEA-S concentration and PS ( r = −0.308, P < 0.0001). IMT and PS were significantly greater in patients with lower concentrations of DHEA-S (<1000 ng/ml) than in patients with higher concentrations of DHEA-S (1.07 ± 0.30 mm versus 0.91 ± 0.19 mm, P < 0.0001, and 5.5 ± 4.2 versus 3.1 ± 3.4, P < 0.0001, respectively). A negative correlation was found between serum DHEA-S concentration and age ( r = −0.488, P < 0.0001). Multiple regression analysis demonstrated that serum DHEA-S concentration was an independent determinant of IMT ( β = −0.289, P < 0.0001) and of PS ( β = −0.301, P < 0.0001). In conclusion, serum DHEA-S concentration is negatively associated with carotid atherosclerosis determined by ultrasonographically evaluated IMT and PS in men with type 2 diabetes.

The Early Dehydroepiandrosterone Sulfate Rise of Adrenarche and the Delay of Pubarche Indicate Primary Ovarian Failure in Turner Syndrome

Girls with Turner syndrome provide the first human model in which adrenal puberty (adrenarche) takes place without gonadal puberty. A wide range of serum dehydroepiandrosterone sulfate (DHEAS) concentrations has been observed, ranging from normal to very elevated. This study attempted to determine whether the course of adrenarche and pubarche is independent of ovarian function. A total of 867 serum DHEAS estimates were made over time in 111 girls with Turner syndrome. Puberty began spontaneously in 22 of these girls, whereas 45 had primary ovarian failure (POF). Serum DHEAS levels were compared with those of 322 healthy girls 3 to 17 years of age. POF was defined as a lack of spontaneous breast development and at least 1 follicle-stimulating hormone (FSH) level of 50 IU/L or higher before estrogen replacement therapy. Age-related serum concentrations of DHEAS were significantly higher in girls with Turner syndrome than in control girls from ages 7 to 17 years. Those with POF had significantly higher age-related levels than did girls experiencing spontaneous puberty at ages 9 to 15 years. Adrenarche occurred at a median age of 8.3 years in girls with POF, compared with 10.5 years for girls with spontaneous puberty and 11 years in normal girls. In both groups with Turner syndrome, mean DHEAS levels correlated closely with mean FSH and luteinizing hormone levels. Pubarche was delayed in girls with POF despite their high serum DHEAS levels. Puberty occurred more than 4.5 years after adrenarche, at a median age of 13 years, in girls with Turner syndrome, whereas in girls with spontaneous puberty, the interval was 1.4 years and the median age at pubarche was 11.9 years. These findings indicate that normally timed adrenarche depends on gonadal function. Normal pubarche represents the conversion of DHEAS to active androgens in the ovaries. Premature adrenarche and pubarche in an otherwise healthy girl may be the first clinical sign of functionally defective ovaries.

Association Between Urinary Albumin Excretion and Serum Dehydroepiandrosterone Sulfate Concentration in Male Patients With Type 2 Diabetes

Cardiovascular disease (CVD) is the leading cause of mortality and morbidity in patients with type 2 diabetes. Both elevated urinary albumin excretion and low serum concentrations of dehydroepiandrosterone (DHEA) are associated with increased CVD mortality. This raises the possibility of DHEA as a causal intermediate linking urinary albumin excretion to CVD. Relationships of urinary albumin excretion to serum DHEA sulfate (DHEA-S) concentration and to major cardiovascular risk factors, including blood pressure, serum lipid concentration, glycemic control (HbA1c), and BMI, were investigated in 357 consecutive men with type 2 diabetes. Serum DHEA-S concentrations were lower in patients with macroalbuminuria (866.5 +/- 523.8 ng/ml, P <0.0001) and in those with microalbuminuria (1,014.4 +/- 525.3 ng/ml, P=0.0006) than in patients with normoalbuminuria (1,232.6 +/- 542.4 ng/ml). Serum DHEA-S concentration correlated inversely with log (urinary albumin excretion) (r=-0.227, P <0.0001). Multiple regression analysis demonstrated that duration of diabetes (beta=0.147, P=0.0075), HbA1c (beta=0.156, P=0.0048), BMI (beta=0.194, P=0.0007), systolic blood pressure (beta=0.195, P=0.0005), and serum DHEA-S concentration (beta=-0.192, P=0.0010) were independent determinants of log (urinary albumin excretion). Serum DHEA-S concentration, which correlated inversely with degree of urinary albumin excretion, may contribute to the link between elevated urinary albumin excretion and higher CVD mortality in male patients with type 2 diabetes.

The Relationship between Serum Dehydroepiandrosterone Sulfate Concentration and Bone Mineral Density, Lipids, and Hormone Replacement Therapy in Premenopausal and Postmenopausal Women

To investigate the relationship between serum dehydroepiandrosterone sulfate (DHEAS) concentration and bone mineral density (BMD), lipids, and hormone replacement therapy (HRT) in postmenopausal women. Two hundred twenty-seven women aged >40 years were admitted to the study and divided into three groups: 61 premenopausal normally menstruating women, 108 postmenopausal women who were not receiving HRT, and 58 postmenopausal women receiving HRT. DHEAS levels and lipid patterns were measured. BMD measurements of the lumbar spine (L1-L4) were performed by dual-energy x-ray absorptiometry (DXA). A positive correlation between DHEAS levels and BMD was found in all three groups. A linear regression model was used to assess the effect of age, body mass index (BMI), parity, and BMD of lumbar vertebrae (L1-L4) on changes in the serum level of DHEAS and found that aging and BMD at the spine had a significant association with serum level of DHEAS and only aging after adjustment for age, BMI, parity, and lipid patterns among the three groups. Age (RR 0.80), DHEAS (RR 0.98), and osteoporosis/osteopenia rate (RR 24.94) were also found to be independent influencing factors for HRT use. A positive correlation between DHEAS levels and BMD was found in all three groups. Our study confirms earlier reports that DHEAS levels decrease with age in premenopausal and, especially, postmenopausal women regardless of estrogen treatment. DHEAS levels in postmenopausal women were not associated with atherogenic lipid patterns in the present study.