Plasma Dehydroepiandrosterone Sulfate Research Articles

AMBULATORY BLOOD PRESSURE MONITORING BEFORE AND AFTER TREATMENT IN SECONDARY FORMS OF HYPERTENSION

Objective: Studies using ambulatory blood pressure (BP) monitoring (ABPM) have reported that in some secondary forms of hypertension the normal nocturnal BP decrease is blunted. Design and method: The aim of our study was to compare the nocturnal BP decrease in patients with secondary hypertension before and after treatment. ABPM was performed using the validated Meditech ABPM-06. ABPM readings were obtained at 30-minute intervals for 24-hour in patients with secondary hypertension before and after treatment. The diagnosis of secondary hypertension was based on the history and laboratory data: plasma and urinary electrolytes, renal function, calcium-phosphorus system, the renin-angiotensin-aldosterone system, urinary free cortisol, suppressibility of cortisol after 1 mg dexamethasone, plasma adrenocorticotropic hormone, plasma D4 androstenedione, plasma dehydroepiandrosterone sulphate, plasma 17-alpha hydroxyprogesterone, plasma testosterone, and urinary metanephrine. BP decrease were studied in the following groups: 42 patients with primary aldosteronism (19 men and 23 women; mean age, 44±12 years), 25 patients with adrenal pheochromocytoma (11 men and 14 women; mean age, 42±13 years), and 55 patients with Cushing's syndrome (18 men and 37 women, mean age, 43±13 years). Results: Average systolic/diastolic BP decrease was: before 2/1 mmHg and after 8/6 mmHg treatment in patients with primary aldosteronism. Average systolic/diastolic BP decrease was: before 4/5 mmHg and after 9/12 mmHg treatment in patients with adrenal pheochromocytoma. Average systolic/diastolic BP decrease was: before 3/2 mmHg and after 11/9 mmHg treatment in patients with Cushing's syndrome. All differences in systolic/diastolic BP decrease were statistically significant, with a P value <.001 Conclusions: The results of our study confirm that secondary causes of hypertension lead to a reduced decrease in blood pressure during sleep. After proper treatment reduction in nighttime BP normalizes. A detailed analysis of ABPM can lead us to find the accurate etiology of hypertension.

A liquid chromatography-tandem mass spectrometry method for the analysis of dehydroepiandrosterone sulphate (DHEAs) in serum and plasma with comparison to an immunoassay method in a neonatal population

The measurement of dehydroepiandrosterone-sulphate (DHEAs) is an important second-line test to aid in the diagnosis of premature adrenarche, peripubertal gynaecomastia in males and in identifying the source of elevated androgens in females. Historically, DHEAs has been measured by immunoassay platforms which are prone to poor sensitivity and more importantly poor specificity. The aim was to develop an LC-MSMS method for the measurement of DHEAs in human plasma and serum, develop an in-house paediatric (<6 year old) reference limit and compare the performance against the Abbott Alinity DHEAs immunoassay method.Following pre-treatment with an internal standard, samples were loaded onto EVOLUTE® EXPRESS ABN plate. Analytes were separated with reverse-phase chromatography using ACQUITY® UPLC® HSS T3 2.1 mm × 50 mm, 1.8 μm column. Mass spectrometry detection was performed using a Waters® Xevo TQ-XS in electrospray negative mode. For the paediatric reference range, samples were collected from an inpatient setting (age ≤ 6 years old) with no evidence of adrenal dysfunction or history of/current steroid use. The method comparison was performed using samples from this cohort aged between 0 and 52 weeks.The assay demonstrated linearity up to 15 µmol/L (r2 > 0.99) with a functional sensitivity of 0.1 µmol/L. Accuracy results revealed a mean bias of 0.7% (−14% to 15%) when compared against the NEQAS EQA LC-MSMS consensus mean (n = 48). The paediatric reference limit was calculated as ≤ 2.3 µmol/L (95% C.I. 1.4 to 3.8 µmol/L) for ≤ 6 year olds (n = 38). Comparison of neonatal (<52 weeks) DHEAs with the Abbott Alinity revealed that the immunoassay ran at a 166% positive bias (n = 24) which appeared to lessen with increasing age.Described is a robust LC-MSMS method for the measurement of plasma or serum DHEAs validated against internationally recognised protocols. Comparison of paediatric samples of <52 weeks against an immunoassay platform demonstrated that in the immediate new-born period results generated from the LC-MSMS method offer superior specificity than an immunoassay platform.

Sleep and Anabolic/Catabolic Hormonal Profile in Sedentary Middle-Aged Adults: The FIT-AGEING Study

Sleep quality plays an important role in the modulation of several aging markers. This influence could be explained by aging-induced hormonal changes. Indeed, poor sleep quality has been associated with the development of several endocrine-related health complications. This study examined the relationship of both subjective and objective sleep quantity and quality, with basal levels of selected plasma anabolic and catabolic hormones in sedentary middle-aged adults. A total of 74 volunteers (52.7% women; aged 53.7 ± 5.1) were recruited for this study. Subjective sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI; higher scores indicate worse sleep quality), and objective sleep quality parameters (total sleep time [TST], wake after sleep onset [WASO], and sleep efficiency [SE]) were measured using a wrist-worn accelerometer. Basal levels of plasma dehydroepiandrosterone sulphate (DHEAS), total testosterone, sex hormone binding globulin (SHBG), somatotropin, and cortisol levels, were determined. Free testosterone was calculated from the total testosterone and SHBG levels. No associations of global PSQI score, TST, WASO, and SE with DHEAS, free testosterone, and somatotropin plasma levels were found, neither in men nor in women (all p ≥ 0.05). Global PSQI score was inversely related to cortisol plasma levels in women (p = 0.043). WASO was positively associated with cortisol plasma levels, while SE was negatively associated with cortisol plasma levels in women (all p ≤ 0.027). Sleep quality is not related to levels of plasma anabolic hormones, but to levels of catabolic hormones, in sedentary middle-aged adults. Therefore, these results suggest that potential changes in aging biomarkers associated with sleep disturbances, could be mediated by age-related changes in the catabolic endocrine system.

PSAT045 Spontaneous Adrenal Hemorrhage with Partial Adrenal Insufficiency in a Patient Anticoagulated with Apixaban for Antiphospholipid Syndrome

Abstract Background Addison's disease secondary to adrenal hemorrhage is a rare complication of antiphospholipid syndrome (APLS). Anticoagulation with a direct oral anticoagulant (DOAC) might increase the risk of adrenal hemorrhage. We report a patient who developed bilateral adrenal hemorrhage after starting apixaban for deep venous thrombosis (DVT) and pulmonary embolism (PE) in the setting of latent APLS. Clinical Case A 45-year-old man without significant past medical history presented with a left lower extremity DVT and PE. He had no personal or family history of previous trauma, bleeding or clotting events. He was discharged on apixaban. Three days later he was readmitted with bilateral flank pain. Computerized tomography (CT) imaging showed bilateral adrenal gland edema. He was hemodynamically stable. Due to persistent right flank pain and concern for ileus, CT was repeated and revealed findings concerning for adrenal hemorrhage. He subsequently complained of asthenia. Further testing revealed a reduced morning cortisol of 1.4 ug/dL (reference: 6.0 - 18.4 ug/dL) and an elevated morning ACTH of 149 pg/mL (7.2-63.3 pg/mL). Plasma dehydroepiandrosterone sulphate (DHEA-S) was reduced at 39 mcg/dL (70 - 495 mcg/dL), and epinephrine and norepinephrine were undetectable. Morning plasma aldosterone was undetectable and renin activity was 0.76 ng/mL/h (0.25 - 5.82 ng/mL/h). He was started on stress dose steroids and discharged on maintenance hydrocortisone without reinitiating anticoagulation. Two weeks later, he re-presented with a right lower extremity DVT. An APLS panel revealed elevated anti-beta2 glycoprotein 1 IgG and anti-cardiolipin IgG. Laboratory work-up for other causes of thrombosis, including inherited and acquired thrombophilias, anatomical vascular obstruction, paroxysmal nocturnal hemoglobinuria (PNH), heparin-induced thrombocytopenia (HIT), and myeloproliferative neoplasms (MPN), was unrevealing. Warfarin was started with an international normalized ratio (INR) target range of 2-3. Hydrocortisone was continued at a total daily dose of 30mg. Since discharge, his morning cortisol levels have been low at 4.4-4.9 ug/dL and ACTH has remained high at 92-137 pg/mL, but aldosterone has been variable at &amp;lt;1 to 9 ng/dL, and renin has been normal at 0.35 ng/mL/h. This suggests what transpired had been microthrombi-associated intra-adrenal hemorrhage involving the zona fasciculata with sparing of the glomerulosa. Conclusion This case highlights DOAC-associated adrenal hemorrhage in a patient with underlying APLS, an under-appreciated complication. The extent to which the various layers of the adrenal gland are affected may vary. Since guidelines on the management of patients with partial adrenal insufficiency are lacking, further reporting is needed on long term outcomes and adrenal function of these patients. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Evaluation of Hyperandrogenism in Children with Autism Spectrum Disorder.

This study evaluated 32 children (mean age: 8.5 y) with autism spectrum disorder (ASD) and 23 healthy controls (similar age, sex, and Tanner stage) for hyperandrogenism. These children underwent sexual maturity rating (Tanner staging), ASD severity assessment (Childhood Autism Rating Scale), and quantitative estimation for plasma testosterone, dehydroepiandrosterone sulfate (DHEAS), and androstenedione. There was no significant difference in androgen levels in the two groups. Elevated (> 95 centiles) testosterone, DHEAS, and androstenedione levels were seen in 12.3%, 6.2%, and 9% children with ASD, and 7/9 of these children (78%) with hyperandrogenism had severe ASD. However, there was no significant correlation between ASD severity and androgen levels.

A Liquid Chromatography-Tandem Mass Spectrometry Method for the Analysis of Dehydroepiandrosterone Sulphate (Dheas) in Serum and Plasma with Comparison to an Immunoassay Method in a Neonatal Population

A Liquid Chromatography-Tandem Mass Spectrometry Method for the Analysis of Dehydroepiandrosterone Sulphate (Dheas) in Serum and Plasma with Comparison to an Immunoassay Method in a Neonatal Population

Diagnostic value of studying neurosteroids in patients with Parkinson's disease dementia

Comparative assessment of the level of dehydroepiandrosterone sulfate (DHEA-S) and cortisol in blood plasma in patient's with Parkinson's disease dementia (PDD) in the late stages of disease.

Organic Anion Transporting Polypeptide 2B1 (OATP2B1) Genetic Variants: In Vitro Functional Characterization and Association With Circulating Concentrations of Endogenous Substrates.

Organic anion transporting polypeptide 2B1 (OATP2B1, gene SLCO2B1) is an uptake transporter that is thought to determine drug disposition and in particular, the oral absorption of medications. At present, the clinical relevance of SLCO2B1 genetic variation on pharmacokinetics is poorly understood. We sought to determine the functional activity of 5 of the most common missense OATP2B1 variants (c.76_84del, c.601G>A, c.917G>A, c.935G>A, and c.1457C>T) and a predicted dysfunctional variant (c.332G>A) in vitro. Furthermore, we measured the basal plasma concentrations of endogenous OATP2B1 substrates, namely estrone sulfate, dehydroepiandrosterone sulfate (DHEAS), pregnenolone sulfate, coproporphyrin I (CPI), and CPIII, and assessed their relationships with SLCO2B1 genotypes in 93 healthy participants. Compared to reference OATP2B1, the transport activities of the c.332G>A, c.601G>A and c.1457C>T variants were reduced among the substrates examined (estrone sulfate, DHEAS, CPI, CPIII and rosuvastatin), although there were substrate-dependent effects. Lower transport function of OATP2B1 variants could be explained by diminished cell surface expression. Other OATP2B1 variants (c.76-84del, c.917G>A and c.935G>A) had similar activity to the reference transporter. In the clinical cohort, the SLCO2B1 c.935G>A allele was associated with both higher plasma CPI (42%) and CPIII (31%) concentrations, while SLCO2B1 c.917G>A was linked to lower plasma CPIII by 28% after accounting for the effects of age, sex, and SLCO1B1 genotypes. No association was observed between SLCO2B1 variant alleles and estrone sulfate or DHEAS plasma concentrations, however 45% higher plasma pregnenolone sulfate level was associated with SLCO2B1 c.1457C>T. Taken together, we found that the impacts of OATP2B1 variants on transport activities in vitro were not fully aligned with their associations to plasma concentrations of endogenous substrates in vivo. Additional studies are required to determine whether circulating endogenous substrates reflect OATP2B1 activity.

Effect of Mindfulness-Based Stress Reduction on dehydroepiandrosterone-sulfate in adults with self-reported stress. A randomized trial.

Long‐term stress can lead to long‐term increased cortisol plasma levels, which increases the risk of numerous diseases. Dehydroepiandrosterone (DHEA) and its sulfated form dehydroepiandrosterone‐sulfate (DHEAS), together DHEA(S), have shown to counteract some of the effects of cortisol and may be protective during stress. The program “Mindfulness‐Based Stress Reduction” (MBSR) has shown to have positive effects on stress. The present study examined a possible effect of MBSR on DHEAS in plasma compared to a waiting list and a locally developed stress reduction program (LSR) in people with self‐reported stress. The study was a three‐armed randomized controlled trial conducted in a municipal health care center in Denmark. It included 71 participants with self‐reported stress randomized to either MBSR (n = 24) or LSR (n = 23), or a waiting list (n = 24). Blood samples were collected at baseline and at 12 weeks follow‐up to estimate effects of MBSR on DHEAS. The effect of MBSR on DHEAS was statistically significant compared to both the waiting list and LSR. We found a mean effect of 0.70 µmol/L (95% confidence interval [CI] = 0.18–1.22) higher DHEAS in the MBSR group compared with the waiting list group and a mean effect of 0.54 µmol/L (95% CI = 0.04–1.05) higher DHEAS in the MBSR group compared with the LSR group. Findings indicate an effect on DHEAS of the MBSR program compared to a waiting list and LSR program in people with self‐reported stress. However, we consider our findings hypothesis‐generating and validation by future studies is essential.

Plasma Dehydroepiandrosterone Sulfate and Cardiovascular Disease Risk in Older Men and Women.

Lower dehydroepiandrosterone-sulfate (DHEA-S) levels have been inconsistently associated with coronary heart disease (CHD) and mortality. Data are limited for heart failure (HF) and association between DHEA-S change and events. Assess associations between low DHEA-S/DHEA-S change and incident HF hospitalization, CHD, and mortality in older adults. DHEA-S was measured in stored plasma from visits 4 (1996-1998) and 5 (2011-2013) of the Atherosclerosis Risk in Communities study. Follow-up for incident events: 18 years for DHEA-S level; 5.5 years for DHEA-S change. General community. Individuals without prevalent cardiovascular disease (n = 8143, mean age 63 years). Associations between DHEA-S and incident HF hospitalization, CHD, or mortality; associations between 15-year change in DHEA-S (n = 3706) and cardiovascular events. DHEA-S below the 15th sex-specific percentile of the study population (men: 55.4 µg/dL; women: 27.4 µg/dL) was associated with increased HF hospitalization (men: hazard ratio [HR] 1.30, 95% confidence interval [CI], 1.07-1.58; women: HR 1.42, 95% CI, 1.13-1.79); DHEA-S below the 25th sex-specific percentile (men: 70.0 µg/dL; women: 37.1 µg/dL) was associated with increased death (men: HR 1.12, 95% CI, 1.01-1.25; women: HR 1.19, 95% CI, 1.03-1.37). In men, but not women, greater percentage decrease in DHEA-S was associated with increased HF hospitalization (HR 1.94, 95% CI, 1.11-3.39). Low DHEA-S and change in DHEA-S were not associated with incident CHD. Low DHEA-S is associated with increased risk for HF and mortality but not CHD. Further investigation is warranted to evaluate mechanisms underlying these associations.

The effect of synbiotic on glycemic profile and sex hormones in overweight and obese breast cancer survivors following a weight-loss diet: A randomized, triple-blind, controlled trial.

The investigation was designed to assess the effects of synbiotic supplementation on glycemic profile, insulin-like growth factor-1 (IGF-1) and sex hormones in overweight and obese postmenopausal breast cancer survivors (BCSs) who had hormone-receptor-positive breast cancer. This randomized, triple-blind, placebo-controlled trial was conducted on 76 overweight and obese BCSs aged 57.43 (5.82)years. All participants were given a specified low calorie diet and were randomly assigned into two groups to intake 109CFU/day of synbiotic supplement (n=38) or placebo (n=38) for 8 weeks. Body composition, physical activity, glycemic profile, IGF-1, estradiol, testosterone and dehydroepiandrosterone sulfate (DHEA-S) were measured at baseline and after 8 weeks. A significant reduction in serum insulin (median change (Q1, Q3) from baseline of-1.05 (-2.36, 0.32) μIU/mL; P=0.006) and insulin resistance (HOMA-IR) (mean change (SD) from baseline of-4.0 (0.9); P=0.007) were seen over the 8 weeks in the synbiotic group. However, no significant changes were observed in serum insulin, fasting plasma glucose, HbA1c, HOMA-IR, IGF-1, estradiol, testosterone, DHEA-S and sex hormone binding globulin between-groups at the end of the intervention. Overall, as the 8-week synbiotic consumption compared with placebo had insignificant-reducing effects on glycemic profile, IGF-1 and sex hormones among overweight and obese postmenopausal BCSs, synbiotics may exert considerable beneficial consequences, which need to be further assessed in future clinical trials. IRCT, IRCT2015090223861N1. Registered 02 February 2017, http://www.irct.ir: IRCT2015090223861N1.

MON-188 The Diagnostic Value of DHEAS in Subtyping Patients with Cushing Syndrome

Objective: Serum dehydroepiandrosterone sulfate (DHEAS) can be used to assess the integrity of the hypothalamic-pituitary-adrenal (HPA) axis. The aim of this study was to evaluate the clinical value of DHEAS in differentiating adrenal Cushing syndrome (ACS) from Cushing’ disease (CD). Methods: We recruited 100 patients with Cushing syndrome, 36 with CD and 64 with ACS. 72 sex-, age- and BMI-matched nonfunctional adrenal adenomas (NFAAs) were served as controls. Clinical and laboratory data were collected. DHEAS levels were measured and DHEAS ratio was calculated by dividing the measured DHEAS by the lower limit of the respective reference range (age- and sex-matched). Results: 1) No significant differences in age, sex, or BMI were detected among the NFAAs, ACS and CD groups. Compared to NFAAs group, ACS patients had lower plasma ACTH levels [1.11(1.11,1.74) vs 5.0 ± 2.9 pmol/L, P<0.01], lower DHEAS levels (24.00 ± 20.72 vs 189.05 ± 82.03 ug/dL, P < 0.01) and lower DHEAS ratio [0.58(0.27,0.98) vs 5.34 ± 3.0]; Plasma ACTH (22.12 ± 14.22 pmol/L), DHEAS (309.4 ± 201.1 ug/dL) and DHEAS ratio (10.51 ± 7.65) in CD patients were significantly higher compared to those in NFAAs and ACS patients (all P<0.01). 2) In ACS patients, there were 53 patients with suppressed ACTH level of <2.0 pmol/L, 11 patients without plasma ACTH suppression (≥2.0pmol/L). Compared to NFAAs, lower DHEAS and DHEAS ratio were detected in these two groups, and no significant differences were found in the DHEAS [15(15, 23.5) vs 23.8 ± 14.4 ug/dL, P=0.86] and DHEAS ratio [0.58(0.27, 0.80) vs 1.0(0.25,2.09) ug/dL, P=0.40] between the two groups. 3) ROC analysis showed that the area under the curve (AUC) of plasma ACTH, serum DHEAS and DHEAS ratio in diagnosing 0.954, 0.997 and 0.990 respectively. The optimal cut-off values for DHEAS and its ratio were 79.1ug/dL, and 2.09, respectively. The diagnostic sensitivity and specificity of plasma ACTH (<2.0pmol/L) were 84.1 and 100%, those of DHEAS were 97.5% and 100%, and those of DHEAS ratio were 95% and 100%, respectively. Conclusions: Patients with different subtype of Cushing syndrome showed distinctive DHEAS levels and DHEAS ratio. DHEAS and DHEAS ratio are useful in differential diagnosis of Cushing syndrome. Especially, when the plasma ACTH level is not conclusive. The measurement of DHEAS may offer a supplementary test to diagnosis ACS from CD. Keywords: Adrenal Cushing syndrome; Cushing disease; Adrenocorticotropic hormone; Dehydroepiandrosterone sulfate

Endogenous Testosterone Levels Are Associated with Risk of Type 2 Diabetes in Women without Established Comorbidity.

PurposeThe impact of endogenous androgen levels on the risk of type 2 diabetes in women remains uncertain. The objective was to investigate associations between endogenous androgen levels and risk of type 2 diabetes in young women without established comorbidity.MethodsIn this retrospective cohort study, women aged 18 to 50 years who underwent measurement of plasma testosterone, dehydroepiandrosterone-sulfate (DHEA-S), dihydrotestosterone (DHT), and sex hormone-binding globulin (SHBG) for the first time from January 2007 to December 2015 were included. Androgens were analyzed using tandem liquid chromatography mass spectrometry. Women with established comorbidity were excluded, using Danish healthcare registries. We calculated incidence rate ratios (IRRs, 95% confidence intervals) of type 2 diabetes according to quartiles of plasma androgens using multivariate Poisson regression models.ResultsA total of 8876 women, with a mean ± SD age of 38.5 ± 4.6 years and a median (interquartile range [IQR]) follow-up duration of 8.1 (6.6-9.4) years, were eligible for analyses. During 69 728 person-years, 69 women were diagnosed with type 2 diabetes. Women in the highest quartile of plasma total testosterone and calculated free testosterone displayed increased risk of type 2 diabetes compared with the lowest quartile: IRR 1.97 (1.01; 3.85), P = .048 and IRR 7.32 (2.84; 18.83), P < .001. SHBG was inversely associated with type 2 diabetes, Q4 versus Q1; IRR 0.06 (0.02; 0.21), P < .001. Plasma DHEA-S and DHT were not associated with incident type 2 diabetes.ConclusionsHigher levels of plasma total and free testosterone were associated with increased risk of type 2 diabetes among women.

Associations between dehydroepiandrosterone sulphate (DHEAS) and cognitive function in 5,061 older men and women in the English Longitudinal Study of Ageing

Despite extensive observational and intervention research, the association between concentrations of dehydroepiandrosterone sulfate (DHEAS) and cognition at older ages remains unclear. This study investigated cross-sectional and longitudinal relationships between plasma DHEAS and cognitive function in a large nationally-representative cohort of men and women aged 50 and older. Data were analysed from 5061 participants (mean age 65.1, standard deviation 8.61) who completed memory, verbal fluency and processing speed tests at baseline and two years later. Age, education, marital status, paid employment, depressive symptoms, mobility impairment, coronary heart disease and diabetes were included as covariates, and analyses were stratified by gender. We found positive associations at baseline between DHEAS concentration and aggregate cognition after adjustment for covariates in men (β = 0.049, standard error (s.e.) 0.020, p = 0.015). Longitudinally, DHEAS at baseline predicted cognition two years later in men (β = 0.052, s.e. 0.020, p = 0.010), but not after baseline cognition was taken into account (β = 0.022, s.e. 0.016, p = 0.17), indicating that DHEAS was not associated with rate of cognitive decline. Similar associations were recorded at 6 year follow-up. No significant relationships between DHEAS and cognition were observed among women. We conclude that greater DHEAS concentrations are associated with cognition level at older ages in men, but are unlikely to play a functional role in cognitive decline.

SEX HORMONES CONCENTRATIONS AT DIFFERENT DOPAMINE LEVELS AMONG WOMEN IN THE RUSSIAN ARCTIC

Several studies havebeenpublished on the relationship between the hypothalamic-pituitary-gonadal and dopaminergic systems. However, they are mainly limited to experimental or clinical settings. The aim was to study the activity of the pituitary-gonadal system at different plasma dopamine levels in women living in the Russian Arctic taking into account their physiological state (reproductive age or postmenopause) and place of residence. Methods. Altogether, 72 women of the European North and 126 women of the Asian North aged 21-83 years participated in a cross-sectional study. Serum levels of luteinizing, follicle-stimulating hormones, prolactin, progesterone, total and free testosterone, dehydroepiandrosterone sulfate, estradiol, and dopamine in the blood plasma were estimated. Results. Reference dopamine levels in fertile women of the European North were associated with higher values of prolactin (21.6 ng/ ml), dehydroepiandrosterone sulfate (6.49 pmol / l) and free testosterone (2.2 pg/ml), compared with women with undetectable dopamine levels in blood (11.4 ng/ml; 5.05 pmol/L; 0.7 pg/ml, respectively). In postmenopausal women of the Asian North the abovelimit dopamine levels were associated with lower levels of follicle-stimulating hormones (45.2 IU/L) and progesterone (2.99 nmol/L) and higher concentrations of testosterone (1.42 nmol/L) than in women with reference levels (67.8 IU/L; 3.95 nmol/L; 0.90 nmol/L, respectively). Conclusions. The combination of high prolactin levels with a high content of androgens in fertile women of the European North, especially in the group with reference dopamine levels, can be a risk factor for the occurrence of anovulatory menstruation. In postmenopausal women of the Asian North against the background of general reduced testosterone content, an increase in its level was recorded only in the group of persons with excess dopamine levels.

Inclusion of Endogenous Plasma Dehydroepiandrosterone Sulfate and Mammographic Density in Risk Prediction Models for Breast Cancer.

Endogenous hormones and mammographic density are risk factors for breast cancer. Joint analyses of the two may improve the ability to identify high-risk women. This study within the KARMA cohort included prediagnostic measures of plasma hormone levels of dehydroepiandrosterone (DHEA), its sulfate (DHEAS), and mammographic density in 629 cases and 1,223 controls, not using menopausal hormones. We evaluated the area under the receiver-operating curve (AUC) for risk of breast cancer by adding DHEA, DHEAS, and mammographic density to the Gail or Tyrer-Cuzick 5-year risk scores or the CAD2Y 2-year risk score. DHEAS and percentage density were independently and positively associated with breast cancer risk (P = 0.007 and P < 0.001, respectively) for postmenopausal, but not premenopausal, women. No significant association was seen for DHEA. In postmenopausal women, those in the highest tertiles of both DHEAS and density were at greatest risk of breast cancer (OR, 3.5; 95% confidence interval, 1.9-6.3) compared with the lowest tertiles. Adding DHEAS significantly improved the AUC for the Gail (+2.1 units, P = 0.008) and Tyrer-Cuzick (+1.3 units, P = 0.007) risk models. Adding DHEAS to the Gail and Tyrer-Cuzick models already including mammographic density further increased the AUC by 1.2 units (P = 0.006) and 0.4 units (P = 0.007), respectively, compared with only including density. DHEAS and mammographic density are independent risk factors for breast cancer and improve risk discrimination for postmenopausal breast cancer. Combining DHEAS and mammographic density could help identify women at high risk who may benefit from individualized breast cancer screening and/or preventive measures among postmenopausal women.

Association between Plasma Dehydroepiandrosterone Sulfate and Carotid Intima-Media Thickness among Male and Female Patients with End-Stage Renal Disease on Hemodialysis

Background and Aim: Serum dehydroepiandrosterone sulfate (DHEA-S) is known to be lower in chronic kidney disease (CKD) patients and in those with cardiac disease, and correlates with a poor cardiovascular outcome. This study aimed to assess the correlation between DHEA-S and carotid intima-media thickness (CIMT) as a predictor of cardiovascular disease in hemodialysis (HD) patients. Methods: A total of 88 HD patients were included in this cross-sectional study. They included 53 male (group I) and 35 female patients (group II). In addition to conventional history taking, clinical examination, and routine laboratory investigations, serum DHEA-S and CIMT were measured for all patients. CIMT was measured using B-mode ultrasonography, and the mean of maximum CIMT was recorded. The 2 patient groups were further classified according to the level of DHEA-S. The correlation between serum DHEA-S and CIMT was studied. Results: In male patients, CIMT and age were significantly higher in the group with low DHEA-S level (p = 0.003 and 0.001, respectively), while there was no significant difference in both parameters in females. A higher percentage of HCV-positive patients is present in the male group with low DHEA-S level (p = 0.009). Serum DHEA-S is significantly negatively correlated with CIMT in males (p = 0.003) but not in females, and has a significant negative correlation to age in both genders (p = 0.001 and 0.04, respectively). Conclusion: Endocrinal disturbance representing as lower serum DHEA-S is associated with increased CIMT, which is considered a predictor of cardiovascular disease in male HD patients, although it is largely explained by advancing age.

Low levels of dehydroepiandrosterone sulfate are associated with the risk of developing cardiac autonomic dysfunction in elderly subjects.

To assess the relationships between serum dehydroepiandrosterone sulfate (DHEA-S) levels and heart rate variability (HRV) among different age groups. Forty-five healthy men were divided into 3 groups: young age (YA; 20-39 yrs; n = 15), middle age (MA; 40-59 yrs; n = 15) and old age (OA; ≥ 60 yrs; n = 15). Hemodynamic parameters, linear analyses of HRV and concentrations of cortisol and DHEA-S were measured at rest. The OA group presented a higher resting heart rate (84.3 ± 4.6 bpm) than the YA group (72.0 ± 4.4 bpm; p < 0.05). The YA group showed an attenuated variance of HRV (2235.1 ± 417.9 ms2) compared to the MA (1014.3 ± 265.2 ms2; p < 0.05) and OA (896.3 ± 274.1 ms2; p < 0.05) groups, respectively. The parasympathetic modulation of HRV was lower in both the MA (244.2 ± 58.0 ms2) and OA (172.8 ± 37.9 ms2) groups in comparison with the YA group (996.0 ± 255.4 ms2; p < 0.05), while serum DHEA-S levels were significantly lower in both the MA (91.2 ± 19.6 mg/dL) and OA (54.2 ± 17.7 mg/dL) groups compared to the YA group (240.0 ± 50.8 mg/dL; p < 0.05). A positive correlation between lower serum concentrations of DHEA-S and attenuated variance of HRV (r = 0.47, p = 0.031), as well as lower serum concentrations of DHEA-S and decreased parasympathetic modulation of HRV (r = 0.54, p = 0.010), were found. The present study demonstrated that the decline of plasma DHEA-S is associated with reduced cardiac autonomic modulation during the aging process.

Prolactin-Induced Protein is a novel biomarker for Keratoconus

PurposeThe purpose of the study was to investigate the role of Prolactin-Induced Protein (PIP) as a predictive biomarker for Keratoconus (KC). ParticipantsThis study included one hundred and forty-seven patients with KC (105 male, 42 female), and sixty healthy controls (27 male, 33 female). MethodsTears, plasma and saliva samples were collected from all participants. In both KC and healthy groups all collected samples were divided into four age subgroups (15-24y), (25-34y), (35-44y) and (45y and up). Samples were analyzed using western blot (WB) and enzyme-linked immunosorbent assay (ELISA). Areas under the receiver operating characteristic curves (AUROCs) were used to evaluate diagnostic accuracy for distinguishing between KC and healthy eyes. Main outcome measuresDifference in PIP protein levels between patients with KC and healthy controls. ResultsResults showed significant downregulation of PIP expression in all three biological fluids on KC patients when compared to healthy controls, independent of age, sex and severity. Since PIP is a hormonal-regulated protein, we also investigated the expression of major sex hormones. We detected significant upregulation in salivary and plasma Dehydroepiandrosterone sulfate (DHEA-S) levels and significant downregulation of estrone and estriol levels, in KC patients compared to healthy controls, independent of sex, age, and KC severity stage. ROC was used to determine the overall predictive accuracy of this protein in KC. Data showed an area under the curve (AUC) for PIP in tears of 0.937 (95%CI: 0.902–0.971), in plasma of 0.928 (95%CI: 0.890–0.968) and in saliva of 0.929 (95%CI: 0.890–0.968). ConclusionsConclusively, our results show that PIP levels are reduced in all three human biological fluids tested, and may independently or in combination with current imaging techniques aid in screening and diagnosis of KC. Our data revealed that PIP levels can potentially differentiate between disease and healthy cases, and PIP levels are stable in relation to KC severity, sex and age. Moreover, alterations in sex hormone levels in correlation with reduced PIP levels in KC provide an intriguing insight in the underlying KC pathophysiology and highlights the role of PIP as a KC biomarker.

Prospective Study of Endogenous Hormones and Incidence of Venous Thromboembolism: The Atherosclerosis Risk in Communities Study.

Exogenous hormone treatments in women (oral contraceptives and hormone replacement therapy [HRT]) are established risk factors for venous thromboembolism (VTE), but less is known about associations between plasma levels of endogenous hormones and VTE risk. We examined the association of baseline dehydroepiandrosterone sulphate (DHEAS), testosterone and sex hormone-binding globulin (SHBG) with risk of future VTE in men and post-menopausal women in the Atherosclerosis Risk in Communities Study. Testosterone, DHEAS and SHBG were measured in plasma samples collected in 1996 to 1998. Cox proportional hazards models were used to estimate hazard ratios for incident VTE adjusting for age, race/ethnicity, body mass index, height, smoking, estimated glomerular filtration rate and C-reactive protein. All analyses were stratified by sex and by current HRT use in women. Among 3,051 non-HRT-using women, 1,414 HRT-using women and 3,925 men at risk at baseline, 184, 62 and 206 experienced incident VTE after a median follow-up of 17.6 years. Plasma hormones were not associated with incidence of VTE among men and non-HRT-using women, although lower plasma DHEAS, when modelled using quartiles or restricted cubic splines, was associated with higher risk of VTE among HRT-using women. This study does not support the existence of an important association between plasma concentrations of endogenous testosterone, DHEAS or SHBG with risk of VTE in middle-aged to older men or post-menopausal women not using HRT.