Low Dehydroepiandrosterone Sulfate Research Articles

Sex-Specific Total Testosterone and Dehydroepiandrosterone Sulfate Status in Noncritically Ill Hospitalized Patients with Coronavirus Disease 2019: A Cross-Sectional Study.

In individuals with coronavirus disease 2019 (COVID-19), male subjects have consistently been linked to poor severity and prognosis. Data on sex hormones in non-critical COVID-19-infected patients are scarce. The aim of this study was to assess the status of total testosterone (TT) and dehydroepiandrosterone sulfate (DHEAS) among noncritical patients with COVID-19 according to sex and their associations with clinical and biochemical features. This cross-sectional observational study was done in the COVID-19 unit of a University hospital during the period of September 2021 to February 2022 among 91 adults (18-65 years) with reverse transcriptase- polymerase chain reaction confirmed noncritical COVID-19 patients. Blood was drawn by venipuncture before receiving steroids between 07:00 to 09:00 a.m. in a fasting state to measure serum TT and DHEAS by chemiluminescent microparticle immunoassay. Diagnosis and classification of COVID-19 were done according to World Health Organization's interim guidance. Age- and sex-specific laboratory reference values were used to classify the TT and DHEAS status of the patients. Only three males (8.1%) had low TT and the rest had normal TT. On the other hand, 15 (27.8%) of the females had high TT with normal levels in the rest. Similarly, 11 (29.7%) males had low DHEAS. Females had low, normal, and high DHEAS in four (7.4%), 48 (88.9%), and two (3.7%) cases respectively. Males with moderate severity of COVID-19 had significantly lower DHEAS (post hoc P=0.038) than the mild group. Both TT (P=0.008) and DHEAS (P=0.023) significantly correlated with neutrophils/lymphocytes ratio and only DHEAS with platelets/lymphocytes ratio (P=0.044) in males. In females, TT significantly correlated with serum sodium (P=0.034). In noncritical COVID-19 patients, substantial gender variations in TT and DHEAS were detected and correlated with severity markers in males.

Dehydroepiandrosterone sulfate to cortisol ratio as a prognostic factor in cirrhotic patients with spontaneous bacterial peritonitis

BackgroundChronic liver disease and decompensated cirrhosis are associated with serious complications; spontaneous bacterial peritonitis is considered one of them that may lead to sepsis and adrenal insufficiency. This trial aimed to study the role of dehydroepiandrosterone sulfate (DHEAS) and DHEAS/cortisol ratio for assessing cirrhotic patients’ adrenal function and as a possible prognostic factor in cirrhotic cases with spontaneous bacterial peritonitis (SBP).Patients and methodsIt was a prospective cohort trial carried out on 100 patients in the Internal Medicine Department, Tanta University Hospital, from June 2021 to July 2022 divided into 2 studied patient groups: group I, 50 cases with liver cirrhosis and sterile ascites; and group II, 50 cases with liver cirrhosis and SBP. Adrenal function was evaluated using serum cortisol levels (9 A.M, 9 P.M, and post synacthen stimulation test), DHEAS level, and DHEAS/cortisol ratio.ResultsThe cirrhotic patients with SBP have significantly decreased DHEAS, decreased DHEAS/cortisol ratio, and high cortisol level post stimulation compared with patients with sterile ascites, cirrhotic cases with decreased DHEAS/cortisol ratio (< 0.65) had elevated C-reactive protein (CRP) levels, a higher model for end-stage liver disease (MELD) score and Child–Pugh score had higher hospital mortality. Both DHEAS and the DHEAS/cortisol ratio were significant predictors of hospital mortality (area under the receiver operating characteristic curve 0.267 and 0.298, respectively). The cirrhotic patients with SBP had decreased DHEAS and DHEAS/cortisol ratio but higher hospital mortality, compared to the cirrhotic patients with sterile ascites.ConclusionsIt was found that a significant increase in cortisol level was after synacthen stimulation, decreased DHEAS, and low DHEAS to cortisol ratio in the cirrhotic patients with spontaneous bacterial peritonitis and was associated with high mortality compared to cirrhotic patients without spontaneous bacterial peritonitis.

Utilizing dehydroepiandrosterone sulfate and its ratio for detecting mild autonomous cortisol excess in patients with adrenal incidentaloma.

Subclinical Cushing syndrome is a condition of mild autonomous cortisol excess (MACE) that lacks typical features of Cushing syndrome but is associated with many complications. It represents a common hormonal dysfunction among patients with adrenal incidentaloma (AI), defined as unexpected masses or lesions found in the adrenal glands during radiological examinations of the chest or abdomen unrelated to adrenal gland assessment. The study evaluated the accuracy of dehydroepiandrosterone sulfate (DHEA-S) and dehydroepiandrosterone sulfate ratio (calculated by dividing the DHEA-S value by the age and sex-adjusted normal range of DHEA-S) in detecting MACE in AI patients. A cross-sectional study was conducted from April 2021 to July 2022 at the Faiha Specialized Diabetes, Endocrine, and Metabolism Centre (FDEMC) in Basrah, southern Iraq, involving 38 AI patients. Comprehensive laboratory and radiological evaluations were performed, including tests for adrenocorticotropic hormone (ACTH), renin, aldosterone, aldosterone/renin ratio (ARR), metanephrine, normetanephrine, cortisol, DHEA-S, and the 1-mg overnight dexamethasone suppression test (1-mg ONDST). Among the AI patients, 14% had MACE. Both DHEA-S ≤75 µg/dL and a DHEA-S ratio ≤1.7 exhibited a sensitivity of 80% each, with specificities of 73.3% and 76.6%, respectively, in diagnosing MACE in individuals aged ≤65 years. The negative predictive values were 95.7% and 95.8%, respectively. Low DHEA-S and DHEA-S ratio had high sensitivity and specificity in predicting MACE among AI patients aged ≤65 years, with strong negative predictive value.

Evaluating individual biomarkers for predicting health risks in zoo-housed chimpanzees (Pan troglodytes) and bonobos (Pan paniscus).

Although biomarkers are often used for predicting morbidity and mortality in humans, similar data are lacking in our closest relatives. This study analyzed 16 biomarkers in zoo-housed chimpanzees and bonobos from serum samples collected during both routine and nonroutine veterinary immobilizations. Generalized linear and generalized linear mixed models were used to determine the efficacy of each biomarker to predict all-cause morbidity, defined as the presence of at least one chronic condition, or cardiac disease as a subset of all-cause morbidity. Cox proportional hazards models were used to examine associations between biomarkers and mortality risk from any cause. Analyses were conducted using two data sets for each species, one with all values retained (chimpanzees: n = 148; bonobos: n = 33) and the other from samples collected during routine immobilizations only (chimpanzees: n = 95; bonobos: n = 23). Consistent results across both data sets in chimpanzees included associations of higher cortisol with all-cause morbidity risk, lower creatinine with cardiac disease risk, and higher creatinine with mortality risk, and in bonobos were increased cardiac disease risk with higher cortisol and lower dehydroepiandrosterone-sulfate, fructosamine, and triglycerides.However, there were some inconsistencies between data sets, such as tumor necrosis factor-α predicting mortality risk positively in chimpanzees when all values were retained, but negatively for routine values only. Despite the close evolutionary relationships between chimpanzees and bonobos, the only result observed in both species was a negative association between albumin and mortality risk in the all values retained data sets. Thus, data suggest some biomarkers may be useful predictors of future health outcomes, although a better understanding of both individual and species variation in biomarkers and their contribution to health risks is needed.

Steroid Sulfation in Neurodegenerative Diseases.

Steroid sulfation and desulfation participates in the regulation of steroid bioactivity, metabolism and transport. The authors focused on sulfation and desulfation balance in three neurodegenerative diseases: Alzheimer´s disease (AD), Parkinson´s disease (PD), and multiple sclerosis (MS). Circulating steroid conjugates dominate their unconjugated counterparts, but unconjugated steroids outweigh their conjugated counterparts in the brain. Apart from the neurosteroid synthesis in the central nervous system (CNS), most brain steroids cross the blood-brain barrier (BBB) from the periphery and then may be further metabolized. Therefore, steroid levels in the periphery partly reflect the situation in the brain. The CNS steroids subsequently influence the neuronal excitability and have neuroprotective, neuroexcitatory, antidepressant and memory enhancing effects. They also exert anti-inflammatory and immunoprotective actions. Like the unconjugated steroids, the sulfated ones modulate various ligand-gated ion channels. Conjugation by sulfotransferases increases steroid water solubility and facilitates steroid transport. Steroid sulfates, having greater half-lives than their unconjugated counterparts, also serve as a steroid stock pool. Sulfotransferases are ubiquitous enzymes providing massive steroid sulfation in adrenal zona reticularis and zona fasciculata.. Steroid sulfatase hydrolyzing the steroid conjugates is exceedingly expressed in placenta but is ubiquitous in low amounts including brain capillaries of BBB which can rapidly hydrolyze the steroid sulfates coming across the BBB from the periphery. Lower dehydroepiandrosterone sulfate (DHEAS) plasma levels and reduced sulfotransferase activity are considered as risk factors in AD patients. The shifted balance towards unconjugated steroids can participate in the pathophysiology of PD and anti-inflammatory effects of DHEAS may counteract the MS.

Performance of DHEAS as a Screening Test for Autonomous Cortisol Secretion in Adrenal Incidentalomas: A Prospective Study.

Autonomous cortisol secretion (ACS) affects up to 30% of patients with adrenal incidentalomas (AIs). The current guidelines for ACS diagnosis are not decisive. A lower dehydroepiandrosterone sulfate (DHEAS) level is a potential biomarker, but the evidence is conflicting. This prospective study aimed to evaluate and validate the ACS screening and diagnostic accuracy of DHEAS. Recruited patients with AI were screened for adrenal medullary and cortisol hypersecretion. The diagnosis of ACS was based on a serum cortisol level ≥ 50 nmol/L following a 1-mg dexamethasone suppression test (DST) and a low-dose DST. Age- and sex-specific DHEAS ratios were also calculated. In the development cohort (45 ACS and 242 non-ACS patients), the areas under the receiver operator characteristic curves (AUCs) of DHEAS and the DHEAS ratio were 0.869 (95% CI 0.824-0.906) and 0.799 (95% CI 0.748-0.844), respectively. The optimal DHEAS cutoff for diagnosing ACS was 60 μg/dL, with a sensitivity of 75.6% (95% CI 60.5-87.1) and a specificity of 81.4% (95% CI 76.4-86.5). The midnight serum cortisol level had moderate diagnostic accuracy [AUC 0.875 (95% CI 0.831-0.911)]. Suppressed adrenocorticotropic hormone (≤2.2 pmol/L) had a lower sensitivity (55.6%), and the 24-hour urinary free cortisol lacked sensitivity and specificity [AUC 0.633 (95% CI 0.603-0.721)]. In the validation cohort (14 ACS and 45 non-ACS patients), the sensitivity and specificity of the optimized DHEAS cutoff were 71.4% (95% CI 41.9-91.6) and 82.2% (95% CI 68.0-92.0), respectively. A single basal measurement of DHEAS is valuable for identifying ACS. Because of its stability and ease of use, the DHEAS level could be used as an ACS screening test.

Interplay of sex hormones and long-term right ventricular adaptation in a Dutch PAH-cohort

To investigate the association between altered sex hormone expression and long-term right ventricular (RV) adaptation and progression of right heart failure in a Dutch cohort of Pulmonary Arterial Hypertension (PAH)-patients across a wide range of ages. In this study we included 279 PAH-patients, of which 169 females and 110 males. From 59 patients and 21 controls we collected plasma samples for sex hormone analysis. Right heart catheterization (RHC) and/or cardiac magnetic resonance (CMR) imaging was performed at baseline. For longitudinal data analysis, we selected patients that underwent a RHC and/or CMR maximally 1.5 years prior to an event (death or transplantation, N=49). Dehydroepiandrosterone-sulfate (DHEA-S) levels were reduced in male and female PAH-patients compared to controls, whereas androstenedione and testosterone were only reduced in female patients. Interestingly, low DHEA-S and high testosterone levels were correlated to worse RV function in male patients only. Subsequently, we analyzed prognosis and RV adaptation in females stratified by age. Females ≤45years had best prognosis in comparison to females ≥55years and males. No differences in RV function at baseline were observed, despite higher pressure-overload in females ≤45years. Longitudinal data demonstrated a clear distinction in RV adaptation. Although females ≤45years had an event at a later time point, RV function was more impaired at end-stage disease. Sex hormones are differently associated with RV function in male and female PAH-patients. DHEA-S appeared to be lower in male and female PAH-patients. Females ≤45years could persevere pressure-overload for a longer time, but had a more severe RV phenotype at end-stage disease.

Oral Contraceptive Use Impairs Muscle Gains in Young Women

Riechman, SE and Lee, CW. Oral contraceptive use impairs muscle gains in young women. J Strength Cond Res 36(11): 3074-3080, 2022-Many active young women use oral contraceptives (OCs), yet their effects on the body composition and exercise performance have not been thoroughly studied. We examined the effects of OCs on muscle responses to a standardized resistance exercise training (RET) program. Two groups of young healthy women (18-29 years old, non-OC: n = 38, OC: n = 34) underwent 10 weeks of whole-body RET (3 days·wk -1 , 3 sets, 6-10 repetitions, at 75% of maximum strength, 13 exercises). Body composition was determined using hydrostatic weighing, and blood samples were taken before and after training to measure dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), IGF-1, and cortisol levels. There were significant differences in lean mass gains between the groups (non-OC: 3.5 ± 0.4% vs. OC: 2.1 ± 0.5% and non-OC: 1.6 ± 0.2 kg vs. OC: 1.0 ± 0.2 kg, p < 0.05). Plasma concentrations of DHEA, DHEAS, and IGF-1 were significantly lower, and cortisol levels were higher in the OC group before and after training ( p < 0.05). In addition, there were significant differences in lean mass gains depending on the androgenicity of progestin between the non-OC and medium-high groups (non-OC: 1.6 ± 0.2 kg, Low = 1.1 ± 0.2 kg, med-high = 0.3 ± 0.5 kg, p < 0.05). Oral contraceptive use impaired lean mass gains in young women after RET and was associated with lower DHEA, DHEAS, and IGF-1 and higher cortisol. The diminished lean mass gain may be related to the effect of OCs on anabolic and catabolic hormone levels or the androgenicity of progestin that may bind to androgen receptors and inhibit its function.

Steroid Sulfation in Adrenal Tumors.

The adrenal cortex produces specific steroid hormones including steroid sulfates such as dehydroepiandrosterone sulfate (DHEAS), the most abundant steroid hormone in the human circulation. Steroid sulfation involves a multistep enzyme machinery that may be impaired by inborn errors of steroid metabolism. Emerging data suggest a role of steroid sulfates in the pathophysiology of adrenal tumors and as potential biomarkers. Selective literature search using "steroid," "sulfat*," "adrenal," "transport," "mass spectrometry" and related terms in different combinations. A recent study highlighted the tissue abundance of estrogen sulfates to be of prognostic impact in adrenocortical carcinoma tissue samples using matrix-assisted laser desorption ionization mass spectrometry imaging. General mechanisms of sulfate uptake, activation, and transfer to substrate steroids are reasonably well understood. Key aspects of this pathway, however, have not been investigated in detail in the adrenal; these include the regulation of substrate specificity and the secretion of sulfated steroids. Both for the adrenal and targeted peripheral tissues, steroid sulfates may have relevant biological actions beyond their cognate nuclear receptors after desulfation. Impaired steroid sulfation such as low DHEAS in Cushing adenomas is of diagnostic utility, but more comprehensive studies are lacking. In bioanalytics, the requirement of deconjugation for gas-chromatography/mass-spectrometry has precluded the study of steroid sulfates for a long time. This limitation may be overcome by liquid chromatography/tandem mass spectrometry. A role of steroid sulfation in the pathophysiology of adrenal tumors has been suggested and a diagnostic utility of steroid sulfates as biomarkers is likely. Recent analytical developments may target sulfated steroids specifically.

Circulating dehydroepiandrosterone sulfate level and cardiovascular or all-cause mortality in the elderly population: a meta-analysis.

Studies have yielded contradictory results concerning the association between dehydroepiandrosterone sulfate (DHEAS) and mortality in the elderly population. This meta-analysis aimed to evaluate the association of low serum DHEAS level with cardiovascular or all-cause mortality in the elderly population. A comprehensive literature search was conducted in PubMed and Embase databases up to 4 February, 2019. Longitudinal observational studies reporting multivariate adjusted risk ratio (RR) and corresponding 95% confidence intervals (CI) for cardiovascular or all-cause mortality with respect to baseline low DHEAS level were included. Both fixed-effect and random effect model were used to pool the overall risk estimate. Methodological quality of the included studies was evaluated using a 9-point Newcastle-Ottawa Scale. Six prospective studies enrolling 6,744 individuals were identified. Five studies were graded as high methodological quality. When compared the lowest to the reference higher circulating DHEAS level, the pooled RR of all-cause and cardiovascular mortality was 1.46 (95% CI: 1.25-1.70) and 1.49 (95% CI: 1.11-1.99), respectively. Subgroup analysis indicated that the association of low DHEAS level with all-cause mortality risk was only found in men (RR 1.41;95% CI: 1.18-1.69) but not in women (RR 1.72; 95% CI: 0.99-2.99). This meta-analysis provides evidence that low circulating DHEAS level is associated with increased risk all-cause mortality in the elderly population.

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.

Low serum DHEA-S is associated with impaired lung function in women.

BackgroundEmerging evidence suggests that androgens and estrogens have a role in respiratory health, but it is largely unknown whether levels of these hormones can affect lung function in adults from the general population. This study investigated whether serum dehydroepiandrosterone sulfate (DHEA-S), a key precursor of both androgens and estrogens in peripheral tissues, was related to lung function in adult women participating in the European Community Respiratory Health Survey (ECRHS).MethodsLung function and serum DHEA-S concentrations were measured in n = 2,045 and n = 1,725 women in 1999–2002 and in 2010–2013, respectively. Cross-sectional associations of DHEA-S levels (expressed as age-adjusted z-score) with spirometric outcomes were investigated, adjusting for smoking habits, body mass index, menopausal status, and use of corticosteroids. Longitudinal associations of DHEA-S levels in 1999–2002 with incidence of restrictive pattern and airflow limitation in 2010–2013 were also assessed.FindingsWomen with low DHEA-S (z-score<-1) had lower FEV1 (% of predicted, adjusted difference: -2.2; 95%CI: -3.5 to -0.9) and FVC (-1.7; 95%CI: -2.9 to -0.5) and were at a greater risk of having airflow limitation and restrictive pattern on spirometry than women with higher DHEA-S levels. In longitudinal analyses, low DHEA-S at baseline was associated with a greater incidence of airflow limitation after an 11-years follow-up (incidence rate ratio, 3.43; 95%CI: 1.91 to 6.14).InterpretationLow DHEA-S levels in women were associated with impaired lung function and a greater risk of developing airflow limitation later in adult life. Our findings provide new evidence supporting a role of DHEA-S in respiratory health.FundingEU H2020, grant agreement no.633212

Low serum estradiol levels are related to Mycobacterium avium complex lung disease: a cross-sectional study

BackgroundThe risk factors for Mycobacterium avium complex lung disease (MAC-LD) are not well known. We hypothesized that low serum estradiol (E2) levels are related to MAC-LD as most patients with MAC-LD are postmenopausal women.MethodsThis cross-sectional study compared patients with MAC-LD and healthy controls. Study subjects were postmenopausal women aged 65 years or younger. Serum testosterone, dehydroepiandrosterone sulfate (DHEA-S), and E2 levels were measured and categorized as high or low based on median levels. We performed multivariate analysis, receiver operating characteristic (ROC) curve analysis, and age- and body mass index (BMI)-matched subgroup analysis to evaluate the association between low serum E2 levels and MAC-LD.Additionally, using blood samples obtained for other clinical studies, the levels of sex steroid hormones were compared between age- and BMI-matched MAC-LD and bronchiectasis female patients without non-tuberculosis mycobacterial infections (non-NTM BE).ResultsForty-two patients with MAC-LD and 91 healthy controls were included. The median E2 (2.20 pg/mL vs. 15.0 pg/mL, p < 0.001), testosterone (0.230 ng/L vs. 0.250 ng/L, p = 0.005), and DHEA-S (82.5 μg/dL vs. 114.0 μg/dL, p < 0.001) levels were lower in the MAC-LD group than in the control group. Multivariate analysis revealed that low serum E2 (adjusted odds ratio = 34.62, 95% confidence interval = 6.02–199.14) was independently related to MAC-LD, whereas low DHEA-S and testosterone were not. ROC analysis illustrated a strong relationship between low serum E2 levels and MAC-LD (area under the curve = 0.947, 95% confidence interval = 0.899–0.995). Even the age- and BMI-matched subgroup analysis of 17 MAC-LD patients and 17 healthy controls showed lower serum E2 in MAC-LD patients than in healthy controls. Additionally, serum E2 levels of 20 MAC-LD patients were lower than plasma E2 levels of 11 matched non-NTM BE patients (1.79 pg/mL vs. 11.0 pg/mL, p < 0.001).ConclusionsLow serum E2 levels were strongly related to MAC-LD in 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.

Flavonoid Intake and Plasma Sex Steroid Hormones, Prolactin, and Sex Hormone-Binding Globulin in Premenopausal Women.

Background: Flavonoids potentially exert anti-cancer effects, as suggested by their chemical structures and supported by animal studies. In observational studies, however, the association between flavonoids and breast cancer, and potential underlying mechanisms, remain unclear. Objective: To examine the relationship between flavonoid intake and sex hormone levels using timed blood samples in follicular and luteal phases in the Nurses’ Health Study II among premenopausal women. Methods: Plasma concentrations of estrogens, androgens, progesterone, dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), prolactin, and sex hormone-binding globulin (SHBG) were measured in samples collected between 1996 and 1999. Average flavonoid were calculated from semiquantitative food frequency questionnaires collected in 1995 and 1999. We used generalized linear models to calculate geometric mean hormone concentrations across categories of the intake of flavonoids and the subclasses. Results: Total flavonoid intake generally was not associated with the hormones of interest. The only significant association was with DHEAS (p-trend = 0.02), which was 11.1% (95% confidence interval (CI): −18.6%, −3.0%) lower comparing the highest vs. lowest quartile of flavonoid intake. In subclass analyses, the highest (vs. lowest) quartile of flavan-3-ol intake was associated with significantly lower DHEAS concentrations (−11.3% with 95% CI: −18.3%, −3.7%, p-trend = 0.01), and anthocyanin intake was associated with a significant inverse trend for DHEA (−18.0% with 95% CI: −27.9%, −6.7%, p-trend = 0.003). Conclusion: Flavonoid intake in this population had limited impact on most plasma sex hormones in premenopausal women. Anthocyanins and flavan-3-ols were associated with lower levels of DHEA and DHEAS.

Dehydroepiandrosterone Supplementation May Benefit Women with Asthma Who Have Low Androgen Levels: A Pilot Study.

IntroductionAmong individuals with severe asthma, FEV1 is low in individuals with low dehydroepiandrosterone (DHEA) sulfate (DHEAS) levels. In the Severe Asthma Research Program (SARP), no women with DHEAS > 200 μg/dL had an FEV1 < 60% predicted. DHEA has benefited patients with COPD and pulmonary hypertension in small trials. Therefore, we hypothesized that DHEA supplementation may improve FEV1 in asthmatic women with low DHEAS.MethodsPremenopausal, nonsmoking, otherwise healthy women, 18-50 years old, with mild or moderate asthma and baseline FEV1 > 60% predicted received 100 mg DHEA orally every 12 h for 2 weeks. Spirometry and DHEAS were measured at the initial visit and 2 weeks later, after completion of DHEA treatment. Based on our previous work, the primary outcome variable for this pilot study was post-albuterol spirometry in the low-DHEAS group. Subjects also continued their other routine asthma management.ResultsSerum DHEAS increased with DHEA treatment in women with starting DHEAS < 200 µg/dL: this increase was from 71 ± 23 to 725 ± 295 µg/dL (n = 10; p = 0.0001). The increase in the high-DHEAS group was smaller. Post-albuterol FEV1 increased by 51 mL, from 3.026 ± 0.5 to 3.077 ± 0.49 L (n = 10; p = 0.034 by paired t test, significant after Bonferroni), in women with low DHEAS. In the high-DHEAS group (baseline DHEAS ≥ 200 µg/dl), post-albuterol FEV1 did not change significantly (n = 3, p = NS). Three subjects were excluded: one had comorbid COPD, one could not perform spirometry, and one did not take the DHEA. There were no adverse effects of DHEA treatment in this trial.ConclusionsEndocrine treatments (corticosteroids) are a mainstay of anti-inflammatory management for moderate and severe asthma. Their use has improved asthma outcomes. Androgens also reduce airway inflammation and promote airway smooth muscle relaxation, but are rarely used clinically for asthma treatment. Our results suggest that the over-the-counter steroid DHEA may improve lung function in asthma outcomes among women with DHEAS < 200 ug/dL.

Dehydroepiandrosterone Sulfate and Free Testosterone but not Estradiol are Related to Muscle Strength and Bone Microarchitecture in Older Adults.

The study aimed to elucidate the relationship between sex steroids and muscle mass, muscle strength, and trabecular bone score (TBS) in a community-dwelling aged population. We analyzed 922 men > 60years of age and 1244 postmenopausal women. Weak muscle strength was defined as hand grip strength < 26kg for men and < 18kg for women, whereas degraded bone microarchitecture was defined as a TBS ≤ 1.2. The mean age was 70.2 ± 6.8years for men and 71.2 ± 6.7years for women. Participants within higher dehydroepiandrosterone sulfate(DHEAS) and free testosterone (FT) tertiles were likely to be younger, have greater muscle mass, and have stronger hand grip strength. Based on logistic regression models, men within the lowest FT tertile had weaker muscle strength compared to those in the highest tertile (adjusted odds ratio [OR] 2.28; 95% confidence interval [CI] 1.33-3.91). Women within the lowest DHEAS and FT tertile had weaker muscle strength compared to those in the highest tertile (adjusted OR for DHEAS 1.42; 95% CI 1.02-1.99; adjusted OR for FT 1.77, 95% CI 1.26-2.48). Moreover, men within the lowest FT tertile exhibited degraded bone microarchitecture compared to those in the highest tertile (adjusted OR 2.57, 95% CI 1.46-4.51). However, estradiol was not related to muscle strength or bone microarchitecture in both sexes. In conclusion, in aged men, serum FT was closely associated with muscle strength and bone microarchitecture and in postmenopausal women, serum DHEAS and FT were related to muscle strength.

Association between locomotive syndrome and blood parameters in Japanese middle-aged and elderly individuals: a cross-sectional study

BackgroundLocomotive syndrome (LS) is associated with weakness and loss of function in the musculoskeletal organs. We aimed to determine the association between LS components and blood parameters in middle-aged and elderly individuals.MethodsWe included 223 middle-aged and elderly individuals in this study (104 men and 119 women; age: 40–85 years). All participants were asked to fast for at least 3 h before the venous blood samples were obtained and the hemoglobin, total protein, glycated hemoglobin (HbA1c), growth hormone, albumin and lipid profile were measured. Three functional tests, the stand-up test, the two-step test, and the 25-question geriatric locomotive function scale (GLFS) were used to assess the risk of LS. Walking speed was assessed by the 10-m walking test. Maximal isometric muscle strengths of the knee extensors were examined, and the weight bearing index (knee extension strength/body weight) was calculated. To assess an independent association between blood parameters and LS, the area under the receiver operating characteristic curve analysis (area under the curve, sensitivity, and specificity) and a binary logistic regression analysis were performed with adjustment for age.ResultsOf the 223 subjects, 119 (53.3%) fulfilled the diagnostic criteria for LS (including a two-step test score < 1.3, difficulty with one-leg standing from 40 cm in the stand-up test, and a 25-question GLFS score ≥ 7). Increased levels of HbA1c were significant risk factors for LS with an OR of 2.62 (OR95%CI = 1.43–4.80), as determined by a logistic regression analysis. Additionally, dehydroepiandrosterone-sulfate (DHEA-S) levels were significant only in the male subjects (OR = 0.992 [OR95%CI = 0.986–0.998]), at a threshold of 88 (AUC; 0.70, sensitivity; 79.6%, specificity; 49.1%). Moreover, 101 of 223 participants (41 men, 60 women) were analyzed for serum albumin levels, with a prevalence of LS at 55.4%, indicating that low levels of albumin were significant risk factors for LS (OR = 0.148 [OR95%CI = 0.023–0.954], p = 0.0445).ConclusionsThese results suggest that higher HbA1c and lower albumin are associated with the prevalence of LS in Japanese middle-aged and elderly individuals. Furthermore, low DHEA-S levels may be useful screening tools for LS in men.

Lower DHEA-S levels predict disease and worse outcomes in post-menopausal women with idiopathic, connective tissue disease- and congenital heart disease-associated pulmonary arterial hypertension.

High oestradiol (E2) and low dehydroepiandrosterone-sulfate (DHEA-S) levels are risk factors for pulmonary arterial hypertension (PAH) in men, but whether sex hormones are related to PAH in women is unknown.Post-menopausal women aged ≥55 years with PAH were matched by age and body mass index to women without cardiovascular disease. Plasma sex hormone levels were measured by immunoassay.Lower levels of DHEA-S (p<0.001) and higher levels of E2 (p=0.02) were associated with PAH. In PAH cases (n=112), lower DHEA-S levels were associated with worse haemodynamics (all p<0.01) and more right ventricular dilatation and dysfunction (both p=0.001). Lower DHEA-S levels were associated with shorter 6-min walking distance (6MWD) (p=0.01) and worse functional class (p=0.004). Each Ln(1 µg·dL-1) decrease in DHEA-S was associated with a doubling in the risk of death (hazard ratio 2.0, 95% CI 1.5-2.7; p<0.001). Higher levels of E2 were associated with shorter 6MWD (p=0.03) and worse functional class (p=0.01).High E2 and low DHEA-S levels are associated with the risk and severity of PAH in post-menopausal women. Hormonal modulation should be studied as a treatment strategy in PAH.

Presence, patterns & predictors of hypocortisolism in patients with HIV infection in India.

Background & objectives:Adrenal insufficiency (AI) is rarely diagnosed in patients with HIV infection, in spite of autopsy studies showing very high rates of adrenal involvement. This study was aimed to determine the presence, patterns and predictors of AI in patients with HIV infection.Methods:Consecutive HIV patients, 18-70 yr age, without any severe co-morbid state, having at least one-year follow up at the antiretroviral therapy clinic, underwent clinical assessment and hormone assays.Results:From initially screened 527 patients, 359 patients having good immune function were analyzed. Basal morning cortisol <6 μg/dl (<165 nmol/l; Group 1), 6-11 μg/dl (165-300 nmol/l; Group 2), 11-18 μg/dl (300-500 nmol/l; Group 3) and ≥18 μg/dl (500 nmol/l; Group 4) were observed in 13, 71, 199 and 76 patients, respectively. Adrenocorticotropic hormone (ACTH) stimulation test revealed 87 patients (24.23%) to have AI. AI in groups 1-4 was 100, 56.34, 17.09 and 0 per cent, respectively. AI patients were more likely to be females (P< 0.05), having longer disease duration (P< 0.05), immune reconstitution inflammatory syndrome, hyperkalaemia (P< 0.01), lower fasting glucose (P< 0.01), dehydroepiandrosterone sulphate (DHEAS) and vitamin D. Regression analysis revealed morning cortisol and DHEAS to be best predictors of AI (P=0.004 and 0.028, respectively).Interpretation & conclusions:AI is a significant problem in HIV-infected individuals, observed in nearly a quarter of patients. Diagnosis warrants high index of suspicion and low threshold for screening, especially in those having low DHEAS and hyperkalaemia. Morning cortisol is a reasonable screening test, with ACTH stimulation warranted to confirm diagnosis, especially in patients with morning cortisol <11 μg/dl (300 nmol/l).