In Utero Chlordecone Exposure and Thyroid, Metabolic, and Sex-Steroid Hormones at the Age of Seven Years: A Study From the TIMOUN Mother-Child Cohort in Guadeloupe.

Background: Chlordecone is an endocrine-disrupting chemical with well recognized estrogenic and progestagenic properties. This organochlorine insecticide was extensively used in the French West Indies from 1973 to 1993 to control the banana root borer. Due to its poor degradation in the environment, permanently polluted soil is responsible for the current contamination of the food chain and human beings. We aimed to examine the relationship of in utero exposure to chlordecone and thyroid (thyroid stimulating hormone [TSH], free tri-iodothyronine [FT3], free thyroxine [FT4]), metabolic (insulin growth-factor 1, leptin, adiponectin), and sex-steroid (dehydroepiandrosterone [DHEA], total testosterone [TT], dihydrotestosterone [DHT], estradiol [E2]) hormone levels in children at the age of seven years who participated in TIMOUN, an ongoing birth cohort in Guadeloupe. Methods: Chlordecone concentrations were measured in cord-blood at delivery. Thyroid, metabolic, and sex-steroid hormone levels were determined in the blood of children at seven years of age. Associations between in utero chlordecone exposure and hormone levels at seven years of age were assessed by multiple linear or logistic regression, controlling for confounding factors. Results: Among the study population (210 boys and 228 girls), chlordecone and hormone measurements were available for 124 boys and 161 girls. We found the third quartile of in utero chlordecone exposure relative to the lowest quartile to be associated with elevated TSH levels in girls and elevated DHEA, TT, and DHT levels in both sexes. Complementary non-linear analysis (spline regression) confirmed a significant non-linear trend for TSH in girls and DHEA and DHT in boys. Conclusion: In utero chlordecone exposure was associated with elevated levels of selected thyroid (TSH) and sex-steroid (DHEA, TT, and DHT) hormones at seven years in a non-monotonic dose response (inverted U) relationship. The implications for future health and reproductive function in puberty and adulthood should be determined.

Immune variations throughout the course of tuberculosis treatment and its relationship with adrenal hormone changes in HIV-1 patients co-infected with Mycobacterium tuberculosis.

HIV infection is a major risk factor predisposing for Mycobacterium tuberculosis infection and progression to active tuberculosis (TB). As host immune response defines the course of infection, we aimed to identify immuno-endocrine changes over six-months of anti-TB chemotherapy in HIV+ people. Plasma levels of cortisol, DHEA and DHEA-S, percentages of CD4+ regulatory T cell subsets and number of IFN-γ-secreting cells were determined. Several cytokines, chemokines and C-reactive protein levels were measured. Results were correlated with clinical parameters as predictors of infection resolution and compared to similar data from HIV+ individuals, HIV-infected persons with latent TB infection and healthy donors. Throughout the course of anti-TB/HIV treatment, DHEA and DHEA-S plasma levels raised while cortisol diminished, which correlated to predictive factors of infection resolution. Furthermore, the balance between cortisol and DHEA, together with clinical assessment, may be considered as an indicator of clinical outcome after anti-TB treatment in HIV+ individuals. Clinical improvement was associated with reduced frequency of unconventional Tregs, increment in IFN-γ-secreting cells, diminution of systemic inflammation and changes of circulating cytokines and chemokines. This study suggests that the combined anti-HIV/TB therapies result in partial restoration of both, immune function and adrenal hormone plasma levels.

Effects of curcumin supplementation on blood glucose, insulin resistance and androgens in patients with polycystic ovary syndrome: A randomized double-blind placebo-controlled clinical trial.

BACKGROUND: Curcumin is a biologically active phytochemical ingredient found in turmeric. It has several pharmacologic effects that might benefit patients with polycystic ovary syndrome (PCOS). OBJECTIVE: We hypothesized curcumin to be effective in improving blood sugar levels, insulin resistance and hyperandrogenism in individuals with PCOS. METHODS: In a randomized double-blind placebo-controlled trial, individuals with PCOS were treated with curcumin (500 mg three times daily) or placebo for 12 weeks. Primary outcome measures were fasting plasma glucose (FPG), fasting insulin (FI), sex hormone levels, and hirsutism (Ferriman-Gallwey [mFG] score). Secondary outcomes included anthropometric measurements. RESULTS: Of 72 randomized individuals, 67 completed the trial. The two groups were comparable at baseline. At the end of the study, FPG and Dehydroepiandrosterone levels had decreased significantly in the intervention group compared to control (difference of change (post-pre) between intervention and placebo groups: -4.11 mg/dL; 95% CI: -8.35, -0.35 mg/dL; p = 0.033 and -26.53 microg/dL; 95% CI: -47.99, -4.34 µg/dL; p = 0.035, respectively). We also observed a statistically non-significant increase (p = 0.082) in Estradiol levels in the intervention group compared to control. No serious adverse events were reported throughout the trial. CONCLUSIONS: Curcumin might be a safe and useful supplement to ameliorate PCOS-associated hyperandrogenemia and hyperglycemia. However, longer trials investigating different dosages in longer durations are needed to underpin these findings.

The paradigm of immunosenescence in atherosclerosis-cardiovascular disease (ASCVD).

The new immunosenescence paradigm (2015) was an attempt to explain a mechanism by which macrophages could be immunosuppressed and dysfunctional, yet paradoxically release proinflammatory factors in an unregulated manner. This mechanism was linked to the loss of dehydroepiandrosterone (DHEA) with aging and thus explained how immunosenescence could be causally related to the risk of stress and/or age-associated chronic diseases. At the center of this paradigm was lipid body negative (LB-) foamy macrophage (CD14+CD16+) which produced human endogenous retrovirus K102 (HERV-K102) particles. HERV-K102 may be a protector foamy virus of humans, and its induction may generate trained innate immunity, a special type of autoimmunity, in response to intracellular pathogens, their constituents, toxins, and/or tumors. Overwhelming evidence now suggests that the proinflammatory foamy macrophages driving ASCVD are LB-. Moreover, the monocyte/macrophage phenotype implicated in atherosclerosis-cardiovascular disease (ASCVD) appears to be the CD14+CD16+ intermediate phenotype. These and other observations directly challenge the cholesterol hypothesis. For the prevention and treatment of ASCVD, it is important to address the putative cause of ASCVD -- immunosenescence, rather than the signs or symptoms such as inflammation or elevated cholesterol. Therefore, strategies to reverse or prevent immunosenescence, which improve or maintain an optimal cortisol/DHEA ratio such as isoflavonoids, would be expected to alleviate not only ASCVD but the risk of many other age-associated chronic diseases. Here, the new immunosenescence paradigm will be appraised for its suitability to explain ASCVD risks.

The adrenal cortex after estradiol or daidzein application in a rat model of the andropause: Structural and hormonal study.

INTRODUCTION AND AIM: Daidzein application may represent an effective and less harmful alternative to indicated, classical estrogenization of ageing men. The aim of this study was to perform structural and hormonal analysis of the adrenal cortex, after estradiol or daidzein supplementation in a rat model of the andropause. MATERIAL AND METHODS: Middle-aged Wistar rats were divided into sham operated (SO; n = 8), orchidectomized (Orx; n = 8), estradiol treated orchidectomized (Orx + E; n = 8) and daidzein treated orchidectomized (Orx + D; n = 8) groups. Estradiol (0.625 mg/kg b.m./day) or daidzein (30 mg/kg b.m./day) were administered subcutaneously for three weeks, while the SO and Orx groups received the vehicle alone. Set objectives were achieved using stereology, histochemistry/immunohistochemistry, immunoassays and ultrastructural analysis. RESULTS: Both estradiol and daidzein treatment significantly increased volumes of the zona glomerulosa cell and nuclei, but decreased circulating aldosterone levels. Estradiol markedly increased volumes of the zona fasciculata cell and nuclei in parallel with significant decrease of the adrenal tissue level of corticosterone, while daidzein significantly decreased both the adrenal and circulating levels of corticosterone. Serum DHEA level and volumes of the zona reticularis cell and nuclei significantly increased upon estradiol treatment, whereas daidzein even stronger increased the circulating level of DHEA. Shunting of the corticosteroidogenesis pathways towards adrenal androgens production, after the treatments, corresponded to the ultrastructural findings and zonal capillary network rearrangements. CONCLUSIONS: Given the coherence of its effects and relative safety, daidzein could be the remedy of choice for the treatment of ageing-caused androgen deprivation and the hypothalamo-pituitary-adrenal axis hyperfunction/related metabolic issues in males.

Osteoprotective Effects of Tribulus terrestris L.: Relationship Between Dehydroepiandrosterone Levels and Ca2+-Sparing Effect.

Osteoporosis is a systemic bone disease that is characterized by impairments in bone strength that predispose an individual to a higher risk of fractures. Despite the various etiologies, undoubtedly the most important factors are aging of the population and hypogonadism. Although several therapeutic options are available, pharmacological treatments have some risks. Among these are increases in the incidence of thrombosis, breast cancer, ovarian cancer, endometrial cancer, and muscle injury, among others. Herbal medication may be an alternative for the treatment of osteoporosis. Thus, the aim of this study was to evaluate the therapeutic effect of a standardized extract of Tribulus terrestris L. (TT) on ovariectomy (OVX)-induced bone loss in rats. Female rats were first subjected to OVX and treated with TT (3, 30, and 300 mg/[kg·day]) or furosemide (25 mg/kg) orally for 28 days. Bone densitometry and tibial histology were performed, and acute renal function and testosterone, dehydroepiandrosterone (DHEA), and estradiol levels were assessed. Prolonged treatment with TT stimulated bone mass gain in all ovariectomized animals, raising bone mass to levels that were similar to sham-operated rats. DHEA levels significantly increased in TT-treated rats. The TT group also had lower calcium (Ca2+) excretion that OVX control and furosemide-treated rats. Finally, the histopathological analyses showed the maintenance of bone turnover in all TT-treated groups. Overall, the results indicate that the standardized extract of T. terrestris exerted a bone-protective effect by increasing bone mineral density. This activity may be at least partially attributable to an increase in serum DHEA levels and a Ca2+-sparing effect.

Effects of dehydroepiandrosterone (DHEA) supplementation on sexual function in premenopausal infertile women.

PURPOSE: To investigate the effects of dehydroepiandrosterone (DHEA) supplementation on female sexual function in premenopausal infertile women of advanced ages. METHODS: This observational study was conducted in an academically affiliated private fertility center. Patients included 87 premenopausal infertile women, 50 of whom completed the study including the Female Sexual Function Index (FSFI) questionnaires and comprehensive endocrine evaluation before and 4-8 weeks after initiating 25 mg of oral micronized DHEA TID. RESULTS: Age of patients was 41.1 ± 4.2 years, BMI 24.4 ± 6.1 kg/m2, 86% were married, and 42% were parous. Following supplementation with DHEA, all serum androgen levels increased (each P < 0.0001), while FSH levels decreased by 2.6 ± 4.4 from a baseline of 10.3 ± 5.4 mIU/mL (P = 0.009). The FSFI score for the whole study group increased by 7% (from 27.2 ± 6.9 to 29.2 ± 5.6; P = 0.0166). Domain scores for desire increased by 17% (P = 0.0004) and by 12% for arousal (P = 0.0122); lubrication demonstrated an 8% trend towards improvement (P = 0.0551), while no changes in domain scores for orgasm, satisfaction, or pain were observed. Women in the lowest starting FSFI score quartile (<25.7), experienced a 6.1 ± 8.0 (34%) increase in total FSFI score following DHEA supplementation. Among these women, improvements in domain categories were noted for desire (40%), arousal (46%), lubrication (33%), orgasm (54%), satisfaction (24%), and pain (25%). CONCLUSIONS: This uncontrolled observational study implies that supplementation with DHEA improves sexual function in older premenopausal women with low baseline FSFI scores.

The impact of an exercise training intervention on cortisol levels and post-traumatic stress disorder in juveniles from an Ugandan refugee settlement: study protocol for a randomized control trial.

BACKGROUND: Latest research demonstrates a significant improvement in stress-related symptoms in psychological disorders as a result of exercise training (ET). Controlled clinical trials further validate the significance of ET by demonstrating lower salivary cortisol levels in patients with post-traumatic stress disorder (PTSD) after intervention. A significant change in cortisol and dehydroepiandrosterone (DHEA) levels can already be found after an 8-12-week ET program. The proposed study aims to investigate the impact of an 8-week ET on PTSD symptoms and changes in cortisol levels in a juvenile refugee sample from the Democratic Republic of the Congo (DRC) at an Ugandan refugee settlement. It is the first to implement an ET intervention in a resource-poor, post-conflict setting. METHODS/DESIGN: In a randomized controlled trial, 198 adolescent participants aged 13-16 years from the DRC who, suffer from PTSD, will be investigated. The participants are based at the Nakivale refugee settlement, an official refugee camp in Uganda, Africa, which is among the largest in the world. The participants will be randomized into an Exercise Training (ET) group with a maximum heart rate (HRmax) of > 60%, an Alternative Intervention (AI) group with low-level exercises, and a Waiting-list Control (WC) group. After the 8-week interventional phase, changes in cortisol awakening response (CAR) and DHEA in the ET group that correspond to an improvement in PTSD symptoms are expected that remain at follow-up after 3 months. DISCUSSION: To date, there is no controlled and reliable longitudinal study examining the effects of an ET program on symptom severity in individuals with PTSD that can be explained with a harmonization of cortisol secretion. The presented study design introduces an intervention that can be implemented with little expenditure. It aims to provide a promising low-threshold and cost-effective treatment approach for the application in resource-poor settings. TRIAL REGISTRATION: German Trials Register, ID: DRKS00014280 . Registered prospectively on 15 March 2018.

The impact of peri-operative dexamethasone administration on the normal hypothalamic pituitary adrenal response to major surgical procedures.

BACKGROUND: Surgical procedures are associated with activation of the hypothalamic-pituitary-adrenal axis (HPA). Studies examining HPA dynamics peri-operatively are limited and the modulating influence of peri-operatively administered glucocorticoids on that is not well established. This investigation examined alterations in HPA function and the impact of dexamethasone (DEX) administration during the peri-operative period. METHODS: We examined HPA function in 297 patients with normal function who had surgical procedures including pituitary mass resection (n = 191), craniotomy (n = 17) and other thoracic/ abdominal/ pelvic surgeries (n = 89). HPA function was assessed by frequent measurements of parameters defining adrenal function: ACTH, cortisol, DHEA and DHEA-S levels for 48 h. DEX was administered as a single dose (2-10 mg) to 30 and as multiple doses (12-36 mg) to 21 patients. The data of DEX-treated subjects within each group were similar and were combined together. RESULTS: Pre-operative data were similar for patients having different surgical procedures. Without DEX exposure, ACTH increased to 225 ± 100 ng/L at 2-4 h and gradually declined to baseline values by 36 h while cortisol levels peaked (39.2 ± 13.2 ug/dL) at 6-8 h declining gradually thereafter. Cortisol rise was paralleled by an equimolar increase in DHEA and a subsequent increase in DHEA-S levels. Single doses of DEX did not influence ACTH or cortisol secretion but suppressed the expected rise in DHEA and DHEA-S levels. Multiple doses of DEX suppressed ACTH and cortisol after the 15th postoperative hour and completely blocked the expected rise in DHEA and DHEA-S levels. CONCLUSIONS: The data provide a detailed overview of HPA function in a large number of subjects who had major surgical procedures. Single and large doses of DEX did not suppress ACTH or cortisol secretion but suppressed adrenal androgen secretion. It took multiple doses of DEX to partially suppress ACTH and cortisol secretion in the peri-operative period.

Serum and follicular fluid testosterone concentrations do not correlate, questioning the impact of androgen supplementation on the follicular endocrine milieu.

Basic research into a possible link between serum and follicular fluid androgen concentrations to detemine whether androgen supplementation in low responders affects follicular endocrine milieu is still lacking. Ninety-seven women (aged 28-43 years) undergoing one natural IVF cycle without any hormone stimulation were analysed. Serum and follicular fluid were collected at the time of follicle aspiration, and the concentrations of LH, total testosterone, oestradiol, dehydroepiandrosterone and anti-Mullerian hormone (AMH) were determined. Serum LH (P = 0.003) and AMH (P = 0.026) concentrations, and follicular fluid AMH (P = 0.015) decreased with increasing age. Within follicular fluid, total testosterone was correlated with oestradiol (P < 0.001) and AMH (P = 0.010); LH correlated with AMH (P = 0.005). Correlation analysis of serum and follicular fluid hormone concentrations revealed that LH, oestradiol and AMH correlated (P < 0.001), whereas testosterone did not. Testosterone serum concentrations did not correlate with other follicular fluid hormones, such as dehydroepiandrosterone, oestradiol and AMH, whereas serum LH correlated with follicular flulid AMH (P < 0.008). Follicular fluid hormone concentrations seem to be independent from serum testosterone. Therefore, it is questionable whether an increase in serum testosterone concentration by androgen supplementation could improve the follicular endocrine milieu.

Initial systemic inflammatory state perturbs exercise training adaptations in elite Taekwondo athletes.

PURPOSE: This study examined ten-week TKD-specific training effects on aerobic capacity, body composition, hormone responses and hematological parameters in elite TKD athletes with varied initial inflammatory states. METHODS: Twenty-two elite college TKD athletes were divided into two groups according to their initial neutrophils-to-lymphocytes ratio (NLR) values: Low NLR (N = 11, 9M/2F, age: 21.6 ± 1.0 yrs; NLR: 1.3 ± 0.2) and High NLR (N = 11, 8M/3F, age: 22.0 ± 0.7 yrs, NLR: 2.5 ± 1.3), and participated in a 10-week TKD-specific training program. Aerobic capacity, body composition, hormonal responses and hematological parameters were measured at baseline and 10-weeks after TKD training. RESULTS: VO2max and shuttle run distance were significantly increased in both groups after training. However, the degree of improvement was greater in the Low NLR group than in the High NLR group. After 10-weeks of exercise training, the High NLR group presented markedly higher fat mass percentage and visceral fat area and significantly lowers DHEA-S to cortisol ratio (D/C ratio) than the Low NRL group. The post-training NLR was negatively correlated with the D/C ratio. Neutrophil counts and NLR were still significantly higher in the High NLR group after training. CONCLUSIONS: This study provides new evidence that young elite TKD athletes with slightly high baseline systemic inflammatory state appear to perturb adaptations to exercise training.

Consumption of green tea epigallocatechin-3-gallate enhances systemic immune response, antioxidative capacity and HPA axis functions in aged male swiss albino mice.

The present investigation assessed the potential of green tea phytochemical epigallocatechin-3-gallate (EGCG) in alleviating age-associated aberrations in immunity, hypothalamus-pituitary-adrenal (HPA) axis and redox homeostasis using 16 months old male Swiss albino mice. Four groups of animals (n = 6 per group) were supplemented with either aqueous EGCG at 25, 50 and 100 mg/kg/animal or vehicle control for 6 weeks. A concurrent analysis of CD4+ and CD8+ lymphocytes in splenocytes, differential leucocyte population, T cell differentiation markers in peripheral blood mononuclear cells (PBMCs), neutrophil functions, immunoglobulins profile in intestine, circulatory HPA axis hormonal levels as well as inflammatory and oxidative stress in the liver was performed. We observed a remarkable increase in plasma dehydroepiandrosterone (DHEA) levels of 100 mg EGCG fed animals while eosinophils and monocytes counts in blood increased. EGCG consumption increased the fraction of CD3+CD8+ cells in splenocytes and CD28 expression on PBMCs. The immunoglobulins profile revealed decreased production of secretory IgA, IgE and IgG1/IgG2a ratio. Liver extracts showed increase in superoxide dismutase activity and total antioxidant capacity while lipid peroxidation along with inflammatory markers (IL-6 and TNF-α) decreased. Our results collectively show that EGCG consumption during aging strengthens systemic immunity by enhancing cellular immune response and simultaneously attenuating antibody response aided by an increase in adrenal DHEA production. Thus, consumption of green tea may be beneficial in alleviating some of the deleterious aspects of aging and immunosenescence in elderly.

Effect of androgen supplementation on 24-hour activity-rest patterns of aged male rhesus macaques.

Like elderly men, old male rhesus macaques show attenuated circulating levels of testosterone and dehydroepiandrosterone sulfate, and many of them also show reduced levels of daytime activity. It is unclear, however, if this age-associated behavioral change is causally related to the underlying decrease in circulating androgen levels. To test this possibility, old male rhesus macaques were given daily supplements of testosterone and DHEA for 6 months, designed to mimic the mean 24-hour circulating hormone patterns of young adults. Compared with the young adults, the old controls showed attenuated daytime activity levels. However, there was no difference between the androgen-supplemented old animals and the aged-matched controls, even after 6 months of treatment. The data suggest that age-associated decreases in circulating androgen levels are unlikely to be a primary reason for altered activity-rest patterns in elderly men, and that androgen supplementation paradigms might not provide any obvious therapeutic benefit.

Serum vitamin D and sex hormones levels in men and women: The Multi-Ethnic Study of Atherosclerosis (MESA).

INTRODUCTION: 25-hydroxyvitamin D [25(OH)D] deficiency has been associated with low testosterone levels in men, but there are conflicting reports of its associations with sex hormones in women. Less is known about whether these associations are independent of adiposity and lifestyle factors, and whether they differ by race/ethnicity. AIM: To examine associations of 25(OH)D concentrations with sex hormone levels. METHODS: Cross-sectional analysis of 3017 men and 2929 women in a multi-ethnic cohort. MAIN OUTCOME MEASURES: Testosterone, estradiol, dehydroepiandrosterone (DHEA), sex hormone binding globulin (SHBG), and free testosterone. RESULTS: The mean (SD) levels of 25(OH)D in men and women were 25.7(10.4) and 26.1(12.0)ng/ml, respectively. In men, after adjusting for demographic and lifestyle variables, a 10ng/ml [25nmol/L] decrease in 25(OH)D was associated with an average difference of -0.70nmol/L (95%CI -1.36, -0.05) in SHBG and 0.02 percent (0.01, 0.04) in free testosterone, but was not associated with low total testosterone level (<10.41nmol/L). In women, a 10ng/ml decrease in 25(OH)D levels was associated with an average difference of -0.01nmol/L (-0.01, -0.00) for estradiol, -8.29nmol/L (-10.13, -6.45) for SHBG, 0.06 percent (0.04, 0.07) for free testosterone, and 0.40nmol/L (0.19, 0.62) for DHEA. There was no significant interaction by race/ethnicity. CONCLUSIONS: Lower 25(OH)D concentrations were associated with lower SHBG levels and higher free testosterone levels in both men and women, and lower estradiol and higher DHEA levels in women, independent of adiposity and lifestyle. We observed no significant association of 25(OH)D with total testosterone in men. Future studies are needed to determine whether vitamin D supplementation influences sex hormone levels.

A low dose (6.5 mg) of intravaginal DHEA permits a strictly local action while maintaining all serum estrogens or androgens as well as their metabolites within normal values.

OBJECTIVE: Serum concentrations of estradiol (E2) and testosterone (testo) measured by mass spectrometry-based assays should remain below the 95th centile measured at 9.3 pg/mL for E2 and 0.26 ng/mL for testo in normal postmenopausal women in order to avoid the risk of non-physiological systemic exposure to elevated serum concentrations of these two sex steroids. METHODS: Serum E2 and testo, as well as dehydroepiandrosterone (DHEA) and nine of its other metabolites, were measured at 10 time intervals over 24 h on the first and seventh days of daily intravaginal administration of 0.50% (6.5 mg) DHEA by validated mass spectrometry-based assays. RESULTS: No biologically significant change in the individual serum concentrations of E2, testo or DHEA was observed. Most importantly, estrone sulfate (E1-S) and the glucuronidated androgen metabolites also remained within normal values, thus confirming the absence of biologically significant systemic exposure in line with intracrinology. Using data from the literature, comparison is made with serum E2 above normal postmenopausal values following administration of 10-µg E2 tablets. CONCLUSION: While the clinical program on vulvovaginal atrophy has shown the efficacy and safety of intravaginal 6.5 mg of DHEA (prasterone), the present data illustrate in detail the serum levels of the individual sex steroids and their metabolites derived from DHEA. The data obtained are in line with the physiology of intracrinology and confirm an action limited to the vagina as the serum concentrations of all sex steroids are maintained within the normal values of menopause, thus protecting the uterus and most likely other tissues.

Serum dehydroepiandrosterone levels are associated with lower risk of type 2 diabetes: the Rotterdam Study.

AIMS/HYPOTHESIS: Previous literature documents controversial results for the impact of dehydroepiandrosterone (DHEA) in glucose metabolism. We aimed to assess the associations between serum levels of DHEA and its main derivatives DHEA sulphate (DHEAS) and androstenedione, as well as the ratio of DHEAS to DHEA, and risk of type 2 diabetes. METHODS: We used data on serum levels of DHEA, DHEAS and androstenedione from 5189 middle-aged and elderly men and women from the prospective population-based Rotterdam Study. Type 2 diabetes was defined as a fasting blood glucose ≥7.0 mmol/l or a non-fasting blood glucose ≥11.1 mmol/l. RESULTS: During a median follow-up of 10.9 years, 643 patients with incident type 2 diabetes were identified. After adjusting for age, sex, cohort, fasting status, fasting glucose and insulin, and BMI, both serum DHEA levels (per 1 unit natural log-transformed, HR 0.76, 95% CI 0.67, 0.87) and serum DHEAS levels (per 1 unit natural log-transformed, HR 0.82, 95% CI 0.73, 0.92) were inversely associated with risk of type 2 diabetes in the total population. Further adjustment for alcohol, smoking, physical activity, prevalent cardiovascular disease, serum total cholesterol, use of lipid-lowering medications, systolic BP, treatment for hypertension, C-reactive protein, oestradiol and testosterone did not substantially affect the association between DHEA and incident type 2 diabetes (per 1 unit natural log-transformed, HR 0.80, 95% CI 0.65, 0.99), but abolished the association between DHEAS and type 2 diabetes. Androstenedione was not associated with risk of type 2 diabetes, nor was DHEAS to DHEA ratio. CONCLUSIONS/INTERPRETATION: DHEA serum levels might be an independent marker of type 2 diabetes.

Hemoglobin during ribavirin-based HCV therapy is closely related to circulating levels of DHEA.

Ribavirin-induced anemia is the major side effect observed during HCV therapy. In an in vitro study, we recently discovered that DHEA can strongly inhibit this adverse event. We also evaluated a possible link between pre-treatment serum DHEA and hemoglobin during HCV therapy. Among the 108 patients of our cohort serum baseline DHEA levels were associated with hemoglobin levels at week 12 of treatment (r = 0.35; P = 0.0021). Patients with low baseline serum DHEA developed severe anemia. A serum level of DHEA less than 1,500 ng/ml had a sensitivity of 94.3% and a positive predictive value of 93.1% for the detection of hemoglobin less than 11 g/dl during the first 12 week of treatment. With pre-treatment DHEA levels below the cutoff, anemia was observed in 24.4% and 60.5% of patients treated with dual therapy and triple therapy, respectively, versus 0% and 15% of patients with higher DHEA levels. At week 12, the mean difference between patients with serum DHEA below and above the cutoff, in terms of absolute hemoglobin for dual and triple therapy groups were 1.2 and 1.7 g/dl, respectively (P = 0.005 and <0.001). Pretreatment DHEA levels are associated with hemoglobin levels during treatment. Based on these data, pretreatment assay of DHEA could be considered systematically in order to propose DHEA supplementation to potentiate the efficacy of the current and future use of ribavirin for HCV and HEV therapy. J. Med. Virol. 89:1033-1039, 2017. © 2016 Wiley Periodicals, Inc.

Dehydroepiandrosterone (DHEA) supplementation results in supraphysiologic DHEA-S serum levels and progesterone assay interference that may impact clinical management in IVF.

PURPOSE: Dehydroepiandrosterone (DHEA) is often prescribed for poor responders in IVF in an effort to improve response to ovarian stimulation. The effect of DHEA supplementation and resultant supraphysiologic DHEA-S serum levels on sex steroid assays has not been evaluated in this population. This study seeks to determine the relationship between DHEA supplementation and progesterone measurements to characterize the degree of interference with particular immunoassays. METHODS: Characterization was accomplished in two phases. First, DHEA-S standard control reagents with no progesterone present were assayed for both DHEA-S and progesterone levels. Second, serum pools from 60 unique IVF patients' serum were used to create six pooled serum samples: three from patients on DHEA supplementation and three from patients not on DHEA supplementation. The three pools were composed of patients whose serum fell into low, medium, and high progesterone ranges. Baseline DHEA-S and progesterone were measured, and the mean level of DHEA-S in the mid-range progesterone pool was used as the mid-point for addition of DHEA-S standard to the serum pools from patients without DHEA supplementation. Progesterone from these pools was then measured on three commercially available immunoassay systems. RESULTS: The first experiment revealed a linear increase in progesterone when analyzing the DHEA-S standard ranging from 0.5 µg/dL [corrected] in the blank control (no DHEA-S) to up to 2.0 µg/dL [corrected] in the high control (DHEA-S >700 µg/dL), [corrected] indicating that the DHEA-S cross-reacts with the progesterone assays. In the second experiment, patients' serum DHEA-S and progesterone were measured from pooled serum samples of those taking DHEA and those not taking DHEA. Adding DHEA-S to the pooled serum of those not taking DHEA resulted in a linear increase in progesterone levels on two of three commercially available immunoassays (p < 0.05). CONCLUSIONS: DHEA-S can interfere with standard progesterone immunoassays used in clinical ART programs, and thus serum progesterone levels in IVF patients on DHEA supplementation may not reflect truly bioactive progesterone.

Clinical evaluation of purified Shilajit on testosterone levels in healthy volunteers.

Purified Shilajit, an Ayurvedic rasayana, was evaluated in healthy volunteers of age between 45 and 55 years for its effect on male androgenic hormone viz. testosterone in a randomised, double-blind, placebo-controlled clinical study at a dose of 250 mg twice a day. Treatment with Shilajit for consecutive 90 days revealed that it has significantly (P < 0.05) increased total testosterone, free testosterone and dehydroepiandrosterone (DHEAS) compared with placebo. Gonadotropic hormones (LH and FSH) levels were well maintained.

Depression, immune function, and early adrenarche in children.

Despite consistent findings of an association between depression and immunity in adult and adolescent populations, little is known about the nature of this relationship at earlier ages. Studies of children have yielded mixed results, suggesting methodological confounds and/or the presence of significant moderating factors. Timing of adrenarche, the first phase of puberty that occurs during late childhood, is a plausible moderator of the depression-immunity relationship in late childhood due to its associations with both the immune system and psychological wellbeing. We hypothesized that: (1) a depression-immunity association exists in children, (2) this association is moderated by adrenarcheal timing, and, (3) this association is also moderated by gender. Data were drawn from a nested study of 103 participants (62 females, Mage=9.5, age range: 8.67-10.21 years) participating in a population based cohort study of the transition from childhood to adolescence (across puberty). Participants in this nested study completed the Children's Depression Inventory 2 (CDI-2) and provided morning saliva samples to measure immune markers (i.e., C-reactive protein, CRP; and secretory immunoglobulin A, SIgA). Using hierarchical regression, inflammation measured by CRP was positively associated with the negative mood/physical symptoms (NM/PS) subscale (ß=0.23, t=2.33, p=0.022) of the CDI-2. A significant interaction effect of SIgA x adrenarcheal timing was found for NM/PS (ß=-0.39, t=-2.19, p=0.031) and Interpersonal Problems (ß=-0.47, t=-2.71, p=0.008). SIgA and NM/PS were positively associated for relatively late developers. SIgA and Interpersonal Problems were positively associated for late developers, and negatively associated for early developers. We suggest that both sets of findings might be partially explained by the immunosuppressive effect of the hormonal changes associated with earlier adrenarche, namely testosterone. These results also suggest that adrenarcheal timing has an effect on the association between depression and immunity, and is therefore an important measure in research with younger populations. Future research should utilize longitudinal designs to demonstrate direction of influence of variables, and use a broader range of pro- and anti-inflammatory markers.