Dehydroepiandrosterone Sulfate Concentrations Research Articles

Isoflavone-Rich Soy Protein Isolate Suppresses Androgen Receptor Expression without Altering Estrogen Receptor-β Expression or Serum Hormonal Profiles in Men at High Risk of Prostate Cancer

The purpose of this study was to determine the effects of soy protein isolate consumption on circulating hormone profiles and hormone receptor expression patterns in men at high risk for developing advanced prostate cancer. Fifty-eight men were randomly assigned to consume 1 of 3 protein isolates containing 40 g/d protein: 1) soy protein isolate (SPI+) (107 mg/d isoflavones); 2) alcohol-washed soy protein isolate (SPI−) (<6 mg/d isoflavones); or 3) milk protein isolate (0 mg/d isoflavones). For 6 mo, the men consumed the protein isolates in divided doses twice daily as a partial meal replacement. Serum samples collected at 0, 3, and 6 mo were analyzed for circulating estradiol, estrone, sex hormone-binding globulin, androstenedione, androstanediol glucuronide, dehydroepiandrosterone sulfate, dihydrotestosterone, testosterone, and free testosterone concentrations by RIA. Prostate biopsy samples obtained pre- and postintervention were analyzed for androgen receptor (AR) and estrogen receptor-β expression by immunohistochemistry. At 6 mo, consumption of SPI+ significantly suppressed AR expression but did not alter estrogen receptor-β expression or circulating hormones. Consumption of SPI− significantly increased estradiol and androstenedione concentrations, and tended to suppress AR expression (P = 0.09). Although the effects of SPI− consumption on estradiol and androstenedione are difficult to interpret and the clinical relevance is uncertain, these data show that AR expression in the prostate is suppressed by soy protein isolate consumption, which may be beneficial in preventing prostate cancer.

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.

Aging, Androgens, and the Metabolic Syndrome in a Longitudinal Study of Aging

Based on Adult Treatment Panel III criteria, we previously reported that the prevalence of the metabolic syndrome (MS) increased with aging; was higher if elevated 2-h plasma postglucose challenge values were included as a criterion; and was greater in men, compared with women. The aim of this study was to evaluate the relationship between the MS and circulating androgen levels in a cohort of men in the Baltimore Longitudinal Study of Aging. Study participants were Caucasian community-dwelling adult men in the Baltimore Longitudinal Study of Aging, who underwent a fasting 2-h oral glucose tolerance test and had serum concentrations of total testosterone (T), dehydroepiandrosterone sulfate, and SHBG levels measured. The prevalence of the MS was 4, 21, 21, and 18% for men between the ages of 20 and 39, 40 and 59, 60 and 79, and 80 and 94 yr, respectively. Total T and SHBG were inversely related to the development of the MS over a mean follow-up period of 5.8 yr (range 1.5-14.0 yr), whereas the free T index and body mass index were positively related to the incidence of the MS. Age alone did not predict the development of the MS, nor did the inclusion of abnormal 2-h plasma postglucose challenge levels in the classification of the MS. Stepwise proportional hazards regression analyses showed that among the various measurements, SHBG levels exerted the greatest influence on development of the MS. The prevalence of the MS increased with aging, and this was associated with lower androgen levels. Lower total T and SHBG predicted a higher incidence of the MS.

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.

Oxcarbazepine and Carbamazepine: Expected and Unexpected Differences and Similarities

Effects of Carbamazepine and Oxcarbazepine on the Reproductive Endocrine Function in Women with Epilepsy. Lofgren E, Tapanainen JS, Koivunen R, Pakarinen A, Isojarvi JI. Epilepsia 2006;47(9):1441–1446. PURPOSE: The aim of the study was to compare the effects of carbamazepine (CBZ) and oxcarbazepine (OXC) on the reproductive endocrine function in women with epilepsy. OXC is a novel antiepileptic drug (AED), and the occurrence of reproductive dysfunction in women treated with OXC monotherapy for epilepsy has not been studied previously. METHODS: Thirty-five women with epilepsy were examined in the Department of Neurology at Oulu University Hospital. Sixteen patients were treated with CBZ monotherapy, and nineteen patients were treated with OXC monotherapy. The subjects were clinically examined, vaginal ultrasonography was performed, and serum sex hormone concentrations were measured. RESULTS: The women taking CBZ or OXC had lower serum testosterone (T) levels and lower free androgen indexes (FAIs) than the control subjects. CBZ medication was associated with increased concentrations of serum sex hormone–binding globulin (SHBG). The patients taking OXC had higher concentrations of dehydroepiandrosterone sulfate (DHEAS) and androstendione (A) than did the women taking CBZ. Moreover, the prevalence of polycystic ovaries (PCOs) was high in the OXC-treated women. CONCLUSIONS: CBZ and OXC have different effects on the reproductive endocrine function. Although both drugs were associated with low serum T concentrations and low FAIs, only OXC was associated with a high frequency of elevated levels of A and DHEAS and with an increased prevalence of PCOs. These findings suggest that OXC may be disadvantageous for women with epilepsy and hyperandrogenism, whereas CBZ may be beneficial for these women.

Serum prolactin concentration and its relationship with dehydroepiandrosterone sulfate concentration in chronic urticaria patients with positive and negative response to autologous serum skin test

Serum prolactin concentration and its relationship with dehydroepiandrosterone sulfate concentration in chronic urticaria patients with positive and negative response to autologous serum skin test

Benign cortisol‐secreting adrenocortical adenomas produce small amounts of androgens

Serum androgen levels are below normal in patients with benign cortisol-secreting adrenocortical adenomas, owing to ACTH suppression. Associated androgen secretion is usually considered as indicative of malignancy. The objective of the study was to analyse the androgen-producing ability of cortisol-secreting adrenocortical adenomas. Retrospective data collection in a single referral hospital centre. Dehydroepiandrosterone sulfate (DHEAS), Delta4androstenedione and testosterone concentrations were measured before and after adrenalectomy and then at 6-month intervals in 20 women (eight cortisol-secreting adrenocortical adenomas, six subclinical cortisol-secreting adrenocortical adenomas, and six nonfunctional adenomas). Before adrenalectomy, serum androgen concentrations were measurable in all women with clinically apparent and subclinical cortisol-secreting adrenocortical adenomas. DHEAS levels were either at the lower end of the normal range or below normal, but were always clearly detectable. Postoperatively, during adrenocortical insufficiency, DHEAS, Delta4androstenedione and testosterone concentrations fell to near the detection limit in all patients with cortisol-secreting adrenocortical adenomas (P = 0.008 for each marker) and showed a similar tendency to fall in all patients with subclinical cortisol-secreting adrenocortical adenomas. Pre- and post-treatment androgen concentrations did not differ in patients with nonfunctional adenomas. Immunohistochemical analysis confirmed CYP17, HSD3B2, SULT2A1 and CYB5 expression by all cortisol-producing tumours. The intensity of CYP17 and SULT2A1 expression was stronger in cortisol-secreting adenomas than in their adjacent normal adrenal tissue. Both clinically apparent and subclinical cortisol-secreting adrenocortical adenomas appear to show moderate autonomous androgen production. Thus, weak androgen secretion in patients with adrenocortical tumours should not necessarily be considered as a sign of malignancy.

Androgenic steroids as unexpected predictors of postpartum psychiatric disturbances

Postpartum psychiatric disorders develop in a significant number of otherwise healthy women. Because of the enormous decline in estradiol and progesterone after delivery, a relationship has been inferred between those changes and the onset of psychiatric symptoms. Little research has been done to characterize a broader range of hormone concentrations over the peripartal time frame and their potential causal relationship with emergent psychiatric disorders. This study investigated associations between nine psychiatric symptom clusters using the Symptom Checklist 90-R against changes in salivary progesterone, dehydroepiandrosterone sulfate (DHEAS), testosterone, estrone, estradiol and estriol concentrations in a cohort of 28 healthy, primigravid women. Concentrations of estradiol and progesterone declined as expected, but were not associated with postpartum psychiatric symptoms. Supra-physiological concentrations of DHEAS and diminished antenatal testosterone were significantly and consistently correlated with anxiety related symptoms and mild psychotic disturbances. These findings are consistent with the pharmacologic properties of these androgenic steroids and suggest that perinatal assessment of DHEAS and testosterone may be useful for prediction of and proactive intervention for postpartum psychiatric disturbances.

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.

Two Years of Treatment With Dehydroepiandrosterone Does Not Improve Insulin Secretion, Insulin Action, or Postprandial Glucose Turnover in Elderly Men or Women

To determine if dehydroepiandrosterone (DHEA) replacement improves insulin secretion, insulin action, and/or postprandial glucose metabolism, 112 elderly subjects with relative DHEA deficiency ingested a labeled mixed meal and underwent a frequently sampled intravenous glucose tolerance test before and after 2 years of either DHEA or placebo. Despite restoring DHEA sulphate concentrations to values observed in young men and women, the changes over time in fasting and postprandial glucose concentrations, meal appearance, glucose disposal, and endogenous glucose production were identical to those observed after 2 years of placebo. The change over time in postmeal and intravenous glucose tolerance test insulin and C-peptide concentrations did not differ in men treated with DHEA or placebo. In contrast, postmeal and intravenous glucose tolerance test change over time in insulin and C-peptide concentrations were greater (P < 0.05) in women after DHEA than after placebo. However, since DHEA tended to decrease insulin action, the change over time in disposition indexes did not differ between DHEA- and placebo-treated women, indicating that the slight increase in insulin secretion was a compensatory response to a slight decrease in insulin action. We conclude that 2 years of replacement of DHEA in elderly men and women does not improve insulin secretion, insulin action, or the pattern of postprandial glucose metabolism.

Higher serum concentrations of DHEAS predict improved nutritional status in helminth-infected children, adolescents, and young adults in Leyte, the Philippines.

Pubertal development and associated downmodulation of proinflammatory cytokines may predict improved nutritional status, independent of chronic parasite infections, in developing countries. We enrolled 731 individuals, aged 7-30 y, from Leyte, the Philippines, where helminth infections and nutritional morbidity are highly prevalent. The following data were collected: venous blood hemoglobin and serum concentrations of ferritin, dehydroepiandrosterone sulfate (DHEAS), C-reactive protein and proinflammatory cytokines (IL-1, IL-6, TNF-alpha, and soluble TNF receptor I); anthropometric measurements to calculate upper arm muscle area Z-score and sum of triceps and subscapular skinfolds Z-score; stool samples to determine Schistosoma japonicum and geohelminth egg counts; and responses to questionnaires assessing socio-economic status. In cross-sectional multilevel linear and logistic regression analyses adjusted for confounders, relations were assessed between 1) DHEAS and nutritional status, 2) DHEAS and proinflammatory cytokines, and 3) nutritional status and proinflammatory cytokines. Independent of age, socio-economic status, and helminth infections, increased levels of DHEAS were associated with improved nutritional status and decreased prevalence of non-iron deficiency anemia in both males and females. DHEAS showed dose-dependent inverse associations with C-reactive protein (P=0.08) and the production of IL-6 (P<0.0001). These inflammatory markers, in turn, were consistently associated with undernutrition and anemia. The results suggest that the puberty-associated rise in DHEAS downmodulates proinflammatory immune responses and thereby reduces undernutrition and anemia in a population experiencing a high burden of chronic helminth infections. This novel regulatory mechanism of inflammation-related nutritional morbidity emphasizes the importance of treating prepubescent children for helminth infections.

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.

Might DHEA be Considered a Beneficial Replacement Therapy in the Elderly?

Dehydroepiandrosterone (DHEA) [prasterone] is typically secreted by the adrenal glands and its secretory rate changes throughout the human lifespan. When human development is completed and adulthood is reached, DHEA and DHEA sulphate (DHEAS) [PB-008] levels start to decline so that at 70-80 years of age, peak DHEAS concentrations are only 10-20% of those in young adults. This age-associated decrease has been termed 'adrenopause', and since many age-related disturbances have been reported to begin with the decline of DHEA/DHEAS levels, this provides a potential opportunity for use of DHEA as replacement therapy. For these reasons, use of DHEA as a replacement therapy in aging men and women has been proposed and this paper outlines the reported beneficial effects of such treatment in humans. Many interesting results have been obtained in experimental animals suggesting that DHEA positively modulates most age-related disturbances. However, renewed interest in DHEA has arisen as a result of recent studies suggesting that DHEA appears to be beneficial in hypoandrogenic men as well as in postmenopausal and aging women. Menopause is the event in a woman's life that induces a dramatic change in the steroid milieu, and use of DHEA as 'replacement treatment' has been reported to restore both the androgenic and estrogenic environment and reduce most of the symptoms of this change. As menopause is the beginning of the biological transition of women towards senescence, it is of great interest to better understand how DHEA might help to solve and/or overcome the problems of this complex stage of life. In men with adrenal insufficiency and hypogonadism without androgen replacement, DHEA administration results in a significant increase in circulating androgens. Though most data are suggestive for use of DHEA as hormonal replacement treatment, more defined and specific clinical trials are needed to uncover all of the 'secrets' and features of this steroid before it can be used as a standard treatment. Furthermore, DHEA is perceived differently around the world, being considered only a 'dietary supplement' in the US, while in many European countries it is considered a 'true hormone' that has not been approved for use as a hormonal treatment by the European health authorities. This overview offers some points of view on use of DHEA as an experimental hormonal replacement therapy.

Changes in Serum Sex Hormone Profiles after Short-term Low-dose Administration of Dehydroepiandrosterone (DHEA) to Young and Elderly Persons

In man, serum concentrations of dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS) decrease with age after the twenties. For this reason, the decline in DHEA and DHEAS concentrations may be related to the development of some chronic diseases that are prevalent in the older age population. In this study, we evaluate the benefit and safety level of DHEA administration to men as a hormone replacement therapy. Twenty-two healthy Japanese males (age 26-63; mean +/- SD, 41.0 +/- 10.0 yrs.) received 25 mg DHEA once a day orally in the morning for two weeks. Serum concentrations of steroid hormones and cytokines were measured before and after the DHEA administration. Glucose tolerance and insulin resistance were also assessed before and after the DHEA administration using a 75 g oral glucose tolerance test and homeostasis model assessment (HOMA-R), respectively. Serum DHEA and DHEAS levels were significantly elevated after the DHEA administration for all ages of test subjects. In subjects who were older than 41 yrs. (older group) serum androstenedione and estradiol levels were elevated after the DHEA administration. Significant negative correlations were observed between the serum DHEA concentration and the serum concentration of fasting insulin, HOMA-R, leptin, and high-sensitivity C-reactive protein for all subjects. Daily administration of 25 mg DHEA increased the serum DHEA, DHEAS, androstenedione, and estradiol levels of the subjects of the older group to the same level as that of younger subjects.

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.

Maternal nerve growth factor serum levels in the perinatal period

Neurotrophins, such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), are potent modulators of neuronal and immune function, and have been implicated recently in diseases associated with pregnancy. In contrast to serum BDNF, which is reportedly suppressed in the perinatal period, regulation of NGF in the perinatal period is unknown. In this study, serum NGF concentrations were measured in 40 pregnant (follow-up: 30th and 37th week of gestation, 1 week and 8 weeks after childbirth) and 40 non-pregnant women. Maternal NGF serum levels did not differ significantly from controls (median: 7.6 pg NGF/ml serum) neither before nor after childbirth, although there was a trend towards increased NGF concentrations at the 37th week of gestation (median: 12.5 pg NGF/ml serum) and 1 week after childbirth (median: 11.6 pg NGF/ml serum). There was no association of maternal NGF with 17β-estradiol, progesterone, dehydroepiandrosterone sulfate (DHEAS) and cortisol concentrations in maternal serum, or maternal depression, as measured by the Edinburgh Postnatal Depression Scale (EPDS). In the non-pregnant control group, NGF serum concentrations were negatively correlated with the number of days since the first day of the menstrual cycle ( r = −0.32, p < 0.05). In conclusion, NGF is not altered during normal pregnancy on a systemic level. In addition, NGF displays a different regulation compared with BDNF during the menstrual cycle.

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.

Melatonin and estrogen in breast cyst fluids

Increased breast cancer risks have been reported among women with gross cystic breast disease (GCBD), although the mechanism for this increase remains unexplained. Relationships between GCBD characteristics, breast cancer risk factors, and the biochemical composition and growth properties of 142 breast cyst fluid (BCF) samples were studied among 93 women with GCBD. Concentrations of melatonin, estrogen (17-beta-estradiol), dehydroepiandrosterone-sulfate (DHEA-S), epidermal growth factor (EGF), transforming growth factor beta (TGF-B1 and TGF-B2), sodium (Na), and potassium (K) were quantified in BCF samples, and human breast cancer cells (MCF-7) were treated with BCF in vitro. Patients were grouped according to BCF Na:K ratios previously linked with increased breast cancer risks (Na:K </= 3, Type 1), and mean concentrations of BCF constituents were compared with low risk (Na:K > 3, Type 2) and mixed cyst groups. Women with larger and more frequently occurring cysts had higher BCF estrogen and DHEA-S, and lower TGF-B1 levels. Women with Type 1 cysts had elevated BCF melatonin, estrogen, DHEA-S, and EGF, and lower concentrations of TGF-B2 compared to women with Type 2 cysts. BCF generally inhibited cell growth relative to serum-treated controls, consistent with previous studies. Melatonin and estrogen in BCF independently predicted growth inhibition and stimulation, respectively. Biological monitoring of BCF may help identify women with GCBD at greatest risk for breast cancer development.

Relationship of alcohol intake and sex steroid concentrations in blood in pre- and post-menopausal women: the European Prospective Investigation into Cancer and Nutrition

Women with a moderate intake of alcohol have higher concentrations of sex steroids in serum, and higher risk of developing breast cancer, compared to non-drinkers. In the present study, we investigate the relationships between alcohol consumption and serum levels of sex steroids and sex-hormone binding globulin (SHBG) in 790 pre- and 1,291 post-menopausal women, who were part of the European Prospective Investigation into Cancer and Nutrition (EPIC). Serum levels of testosterone (T), androstenedione (Delta4), dehydroepiandrosterone sulphate (DHEAS), estrone (E1), estradiol (E2) and SHBG were measured by direct immunoassays. Free T (fT) and free E2 (fE2) were calculated according to mass action laws. Current alcohol intake exposure to alcohol was assessed from dietary questionnaires. Pre-menopausal women who consumed more than 25 g/day of alcohol had about 30% higher DHEAS, T and fT, 20% higher Delta4 and about 40% higher E1, concentrations compared to women who were non-consumers. E2, fE2 and SHBG concentrations showed no association with current alcohol intake. In post-menopausal women, DHEAS, fT, T, Delta4, and E1 concentrations were between 10% and 20% higher in women who consumed more than 25 g/day of alcohol compared to non-consumers. E2 or fE2 were not associated with alcohol intake at all. SHBG levels were about 15% lower in alcohol consumers compared to non-consumers. This study supports the hypothesis of an influence of alcohol intake on sex hormone concentrations in blood.