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Chemosphere Aug 2023Wastewater monitoring and epidemiology have seen renewed interest during the recent COVID-19 pandemic. As a result, there is an increasing need to normalize... (Review)
Review
Wastewater monitoring and epidemiology have seen renewed interest during the recent COVID-19 pandemic. As a result, there is an increasing need to normalize wastewater-derived viral loads in local populations. Chemical tracers, both exogenous and endogenous compounds, have proven to be more stable and reliable for normalization than biological indicators. However, differing instrumentation and extraction methods can make it difficult to compare results. This review examines current extraction and quantification methods for ten common population indicators: creatinine, coprostanol, nicotine, cotinine, sucralose, acesulfame, androstenedione 5-hydroindoleacetic acid (5-HIAA), caffeine, and 1,7-dimethyluric acid. Some wastewater parameters such as ammonia, total nitrogen, total phosphorus, and daily flowrate were also evaluated. The analytical methods included direct injection, dilute and shoot, liquid/liquid, and solid phase extraction (SPE). Creatine, acesulfame, nicotine, 5-HIAA and androstenedione have been analysed by direct injection into LC-MS; however, most authors prefer to include SPE steps to avoid matrix effects. Both LC-MS and GC-MS have been successfully used to quantify coprostanol in wastewater, and the other selected indicators have been quantified successfully with LC-MS. Acidification to stabilize the sample before freezing to maintain the integrity of samples has been reported to be beneficial. However, there are arguments both for and against working at acidic pHs. Wastewater parameters mentioned earlier are quick and easy to quantify, but the data does not always represent the human population effectively. A preference for population indicators originating solely from humans is apparent. This review summarises methods employed for chemical indicators in wastewater, provides a basis for choosing an appropriate extraction and analysis method, and highlights the utility of accurate chemical tracer data for wastewater-based epidemiology.
Topics: Humans; Wastewater; Nicotine; RNA, Viral; SARS-CoV-2; Hydroxyindoleacetic Acid; Androstenedione; Cholestanol; Pandemics; Water Pollutants, Chemical; COVID-19; Solid Phase Extraction; Indicators and Reagents
PubMed: 37201600
DOI: 10.1016/j.chemosphere.2023.138682 -
European Journal of Endocrinology Sep 2023Anorexia nervosa is a primary psychiatric disorder characterized by self-induced negative energy balance. A number of hormonal responses and adaptations occur in... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Anorexia nervosa is a primary psychiatric disorder characterized by self-induced negative energy balance. A number of hormonal responses and adaptations occur in response to starvation and low body weight including changes in adrenocortical hormones. Our objective was to systematically review adrenocortical hormone levels in anorexia nervosa.
DESIGN/METHODS
We searched MEDLINE and EMBASE for studies that reported at least one adrenocortical hormone, including dehydroepiandrosterone (DHEA), DHEA-sulphate (DHEA-S), progesterone, 17-hydroxyprogesterone, pregnenolone, cortisol (serum, urine, cerebrospinal fluid, and hair sample), aldosterone, androstenedione, and testosterone in patients with anorexia nervosa and normal-weight healthy controls from inception until October 2021. Means and standard deviations for each hormone were extracted from the studies to calculate a mean difference (MD). A pooled MD was then calculated by combining MDs of each study using the random-effects model.
RESULTS
We included a total of 101 studies with over 2500 females with anorexia nervosa. Mean cortisol levels were significantly higher in anorexia nervosa as compared to normal-weight controls for multiple forms of measurement, including morning cortisol, 12-hour and 24-hour pooled serum cortisol, 24-hour urine cortisol, and after an overnight dexamethasone suppression test. In contrast, mean serum total testosterone and DHEA-S levels were significantly lower among patients with anorexia nervosa.
CONCLUSIONS
Women with anorexia nervosa have higher cortisol levels and lower DHEA-S and testosterone levels compared to women without anorexia nervosa. This finding is important to consider when evaluating low-weight women for disorders involving the adrenal axis, especially Cushing's syndrome.
Topics: Humans; Female; Anorexia Nervosa; Hydrocortisone; Aldosterone; Progesterone; Dehydroepiandrosterone Sulfate
PubMed: 37669399
DOI: 10.1093/ejendo/lvad123 -
The New England Journal of Medicine Jun 2024Adrenal insufficiency in patients with classic 21-hydroxylase deficiency congenital adrenal hyperplasia (CAH) is treated with glucocorticoid replacement therapy. Control...
BACKGROUND
Adrenal insufficiency in patients with classic 21-hydroxylase deficiency congenital adrenal hyperplasia (CAH) is treated with glucocorticoid replacement therapy. Control of adrenal-derived androgen excess usually requires supraphysiologic glucocorticoid dosing, which predisposes patients to glucocorticoid-related complications. Crinecerfont, an oral corticotropin-releasing factor type 1 receptor antagonist, lowered androstenedione levels in phase 2 trials involving patients with CAH.
METHODS
In this phase 3 trial, we randomly assigned adults with CAH in a 2:1 ratio to receive crinecerfont or placebo for 24 weeks. Glucocorticoid treatment was maintained at a stable level for 4 weeks to evaluate androstenedione values, followed by glucocorticoid dose reduction and optimization over 20 weeks to achieve the lowest glucocorticoid dose that maintained androstenedione control (≤120% of the baseline value or within the reference range). The primary efficacy end point was the percent change in the daily glucocorticoid dose from baseline to week 24 with maintenance of androstenedione control.
RESULTS
All 182 patients who underwent randomization (122 to the crinecerfont group and 60 to the placebo group) were included in the 24-week analysis, with imputation of missing values; 176 patients (97%) remained in the trial at week 24. The mean glucocorticoid dose at baseline was 17.6 mg per square meter of body-surface area per day of hydrocortisone equivalents; the mean androstenedione level was elevated at 620 ng per deciliter. At week 24, the change in the glucocorticoid dose (with androstenedione control) was -27.3% in the crinecerfont group and -10.3% in the placebo group (least-squares mean difference, -17.0 percentage points; P<0.001). A physiologic glucocorticoid dose (with androstenedione control) was reported in 63% of the patients in the crinecerfont group and in 18% in the placebo group (P<0.001). At week 4, androstenedione levels decreased with crinecerfont (-299 ng per deciliter) but increased with placebo (45.5 ng per deciliter) (least-squares mean difference, -345 ng per deciliter; P<0.001). Fatigue and headache were the most common adverse events in the two trial groups.
CONCLUSIONS
Among patients with CAH, the use of crinecerfont resulted in a greater decrease from baseline in the mean daily glucocorticoid dose, including a reduction to the physiologic range, than placebo following evaluation of adrenal androgen levels. (Funded by Neurocrine Biosciences; CAHtalyst ClinicalTrials.gov number, NCT04490915.).
PubMed: 38828955
DOI: 10.1056/NEJMoa2404656 -
Journal of the Endocrine Society Jul 2023Ovarian and adrenal steroidogenesis underlie endocrine-metabolic dysfunction in polycystic ovary syndrome (PCOS). Adipocytes express aldo-keto reductase 1C3 and type 1...
CONTEXT
Ovarian and adrenal steroidogenesis underlie endocrine-metabolic dysfunction in polycystic ovary syndrome (PCOS). Adipocytes express aldo-keto reductase 1C3 and type 1 11β-hydroxysteroid dehydrogenase, which modulate peripheral androgen and cortisol production.
OBJECTIVES
To compare serum adrenal steroids, including 11-oxygenated androgens (11-oxyandrogens), cortisol, and cortisone between normal-weight women with PCOS and body mass index- and age-matched ovulatory women with normal-androgenic profiles (controls), and assess whether adrenal steroids associate with abdominal adipose deposition.
DESIGN
Prospective, cross-sectional, cohort study.
SETTING
Academic medical center.
PATIENTS
Twenty normal-weight women with PCOS and 20 body mass index-/age-matched controls.
INTERVENTIONS
Blood sampling, IV glucose tolerance testing, and total-body dual-energy x-ray absorptiometry.
MAIN OUTCOME MEASURES
Clinical characteristics, hormonal concentrations, and body fat distribution.
RESULTS
Women with PCOS had higher serum total/free testosterone (T) and androstenedione (A4) levels and a greater android/gynoid fat mass than controls (androgens < .001; android/gynoid fat mass ratio, = .026). Serum total/free T and A4 levels correlated positively with android/gynoid fat mass ratio in all women combined ( < .025, all values). Serum 11ß-hydroxyA4, 11-ketoA4, 11ß-hydroxyT, 11-ketoT, cortisol, and cortisone levels were comparable between female types and unrelated to body fat distribution. Serum 11-oxyandrogens correlated negatively with % total body fat, but lost significance adjusting for cortisol. Serum cortisol levels, however, correlated inversely with android fat mass ( = .021), with a trend toward reduced serum cortisol to cortisone ratio in women with PCOS vs controls ( = .075), suggesting diminished 11β-hydroxysteroid dehydrogenase activity.
CONCLUSION
Reduced cortisol may protect against preferential abdominal fat mass in normal-weight PCOS women with normal serum 11-oxyandrogens.
PubMed: 37404244
DOI: 10.1210/jendso/bvad079 -
Endocrine Practice : Official Journal... Aug 2023Hyperandrogenism is frequently observed in patients with polycystic ovary (PCO). The purpose of this study was to develop an easy-to-use tool for predicting polycystic...
OBJECTIVE
Hyperandrogenism is frequently observed in patients with polycystic ovary (PCO). The purpose of this study was to develop an easy-to-use tool for predicting polycystic ovary syndrome (PCOS) and to evaluate and compare the value of androstenedione (Andro) and other hormone indicators in the diagnosis of patients with hyperandrogenic PCOS.
METHODS
This study included 139 women diagnosed with hyperandrogenic PCOS according to the Rotterdam criteria and 74 healthy control women from Shanghai Tenth People's Hospital. The serum hormone levels of the patients and controls were measured using a chemiluminescence immunoassay and incorporated for further analysis.
RESULTS
Total testosterone (TT), Andro, dehydroepiandrosterone sulfate (DHEAS), and free androgen index (FAI) were significantly higher in the PCOS group than the control group. Further, Andro, follicle-stimulating hormone (FSH), luteinizing hormone (LH), TT, FAI, and LH/FSH in the hyperandrostenedione group were higher than the normal Andro group. The Youden index was the highest for Andro (0.65), with 81.82% sensitivity and 83.16% specificity. Correlation analysis showed that FSH, LH, TT, FAI, insulin sensitivity index, and LH/FSH were positively correlated with Andro, while fasting blood glucose and 2-hour postprandial blood glucose were negatively correlated with Andro.
CONCLUSIONS
The model using Andro, TT, and FAI may help to identifying women with undiagnosed PCOS. Serum Andro is a meaningful biomarker for hyperandrogenism in PCOS patients and may further aid disease diagnosis.
Topics: Female; Humans; Polycystic Ovary Syndrome; Testosterone; Androstenedione; Hyperandrogenism; Blood Glucose; China; Luteinizing Hormone; Follicle Stimulating Hormone
PubMed: 37225042
DOI: 10.1016/j.eprac.2023.05.007 -
The vagina as source and target of androgens: implications for treatment of GSM/VVA, including DHEA.Climacteric : the Journal of the... Aug 2023The vagina is traditionally thought of as a passive organ in the female reproductive system, serving primarily as a passageway for menstrual blood, sexual intercourse... (Review)
Review
The vagina is traditionally thought of as a passive organ in the female reproductive system, serving primarily as a passageway for menstrual blood, sexual intercourse and childbirth. However, recent research has shed light on the vagina's role as an endocrine organ that plays a crucial role in female hormonal balance and overall health. Particularly, growing evidence shows that the human vagina can be considered both as source and target of androgens, in view of the novel concept of 'intracrinology'. Besides the well-known role of estrogens, androgens are also crucial for the development and maintenance of healthy genitourinary tissues in women. As androgen levels decline with age, and estrogen levels fall during the menopausal transition, the tissues in the vagina, together with those in the urinary tract, become thinner, drier and less elastic, leading to a variety of uncomfortable and sometimes painful symptoms, clustered in the genitourinary syndrome of menopause (GSM). Given the lack of testosterone-based or androstenedione-based products approved by regulatory agencies to treat GSM, the possibility of using intravaginal prasterone, which works by providing a local source of dehydroepiandrosterone (DHEA) to the vaginal tissues, appears to be a targeted treatment. Further studies are needed to better assess its safety and efficacy.
Topics: Female; Humans; Androgens; Dehydroepiandrosterone; Dyspareunia; Administration, Intravaginal; Vagina; Menopause; Estrogens; Atrophy
PubMed: 37288964
DOI: 10.1080/13697137.2023.2213827 -
European Journal of Pain (London,... Sep 2023The prevalence of chronic non-cancer pain (CNCP) has increased dramatically the past decades, which combined with indiscriminate use of prescribed opioids has become a...
BACKGROUND
The prevalence of chronic non-cancer pain (CNCP) has increased dramatically the past decades, which combined with indiscriminate use of prescribed opioids has become a public health problem. Endocrine dysfunction may be a complication of long-term opioid treatment (L-TOT), but the evidence is limited. This study aimed at investigating the associations between L-TOT and endocrine measures in CNCP patients.
METHODS
Cortisol (spot and after stimulation), thyrotropin (TSH), thyroxin (T4), insulin-like growth factor 1 (IGF-1), prolactin (PRL), 17-hydroxyprogesterone, androstenedione, dehydroepiandrosterone (DHEAS), sex hormone-binding globulin (SHBG), total testosterone (TT) and free testosterone (fT) were measured. Group comparisons were done between CNCP patients in L-TOT and controls as well as between patients on high- or low-dose morphine equivalents.
RESULTS
Eighty-two CNCP patients (38 in L-TOT and 44 controls not receiving opioids) were included. Low TT (p = 0.004) and fT concentrations (p < 0.001), high SHBG (p = 0.042), low DEAS (p = 0.017) and low IGF-1 (p = 0.003) in men were found when comparing those in L-TOT to controls and high PRL (p = 0.018), low IGF-1 standard deviation score (SDS) (p = 0.006) along with a lesser, but normal cortisol response to stimulation (p = 0.016; p = 0.012) were found when comparing L-TOT to controls. Finally, a correlation between low IGF-1 levels and high opioid dose was observed (p < 0.001).
CONCLUSIONS
Our study not only supports previous findings but even more interestingly disclosed new associations. We recommend future studies to investigate endocrine effects of opioids in larger, longitudinal studies. In the meanwhile, we recommend monitoring endocrine function in CNCP patients when prescribing L-TOT.
SIGNIFICANCE
This clinical study found associations between L-TOT, androgens, growth hormone and prolactin in patients with CNCP compared to controls. The results support previous studies as well as add new knowledge to the field, including an association between high opioid dose and low growth hormone levels. Compared to existing research this study has strict inclusion/exclusion criteria, a fixed time period for blood sample collection, and adjustments for potential confounders, which has not been done before.
Topics: Male; Humans; Analgesics, Opioid; Insulin-Like Growth Factor I; Hydrocortisone; Prolactin; Chronic Pain; Testosterone; Growth Hormone
PubMed: 37243401
DOI: 10.1002/ejp.2136 -
Reproductive Sciences (Thousand Oaks,... Nov 2023This cross-sectional study examines the Doi-Alshoumer PCOS clinical phenotype classification in relation to measured clinical and biochemical characteristics of women...
This cross-sectional study examines the Doi-Alshoumer PCOS clinical phenotype classification in relation to measured clinical and biochemical characteristics of women with polycystic ovary syndrome (PCOS). Two cohorts of women (Kuwait and Rotterdam) diagnosed with PCOS (FAI > 4.5%) were examined. These phenotypes were created using neuroendocrine dysfunction (IRMA LH/FSH ratio > 1 or LH > 6 IU/L) and menstrual cycle status (oligo/amenorrhea) to create three phenotypes: (A) neuroendocrine dysfunction and oligo/amenorrhea, (B) without neuroendocrine dysfunction but with oligo/amenorrhea, and (C) without neuroendocrine dysfunction and with regular cycles. These phenotypes were compared in terms of hormonal, biochemical, and anthropometric measures. The three suggested phenotypes (A, B, and C) were shown to be sufficiently distinct in terms of hormonal, biochemical, and anthropometric measures. Patients who were classified as phenotype A had neuroendocrine dysfunction, excess LH (and LH/FSH ratio), irregular cycles, excess A4, infertility, excess T, highest FAI and E2, and excess 17αOHPG when compared to the other phenotypes. Patients classified as phenotype B had irregular cycles, no neuroendocrine dysfunction, obesity, acanthosis nigricans, and insulin resistance. Lastly, patients classified as phenotype C had regular cycles, acne, hirsutism, excess P4, and the highest P4 to E2 molar ratio. The differences across phenotypes suggested distinct phenotypic expression of this syndrome, and the biochemical and clinical correlates of each phenotype are likely to be useful in the management of women with PCOS. These phenotypic criteria are distinct from criteria used for diagnosis.
Topics: Female; Humans; Polycystic Ovary Syndrome; Cross-Sectional Studies; Amenorrhea; Phenotype; Follicle Stimulating Hormone
PubMed: 37217826
DOI: 10.1007/s43032-023-01262-4 -
ELife Feb 2024Primary angle closure glaucoma (PACG) is the leading cause of irreversible blindness in Asia, and no reliable, effective diagnostic, and predictive biomarkers are used...
BACKGROUND
Primary angle closure glaucoma (PACG) is the leading cause of irreversible blindness in Asia, and no reliable, effective diagnostic, and predictive biomarkers are used in clinical routines. A growing body of evidence shows metabolic alterations in patients with glaucoma. We aimed to develop and validate potential metabolite biomarkers to diagnose and predict the visual field progression of PACG.
METHODS
Here, we used a five-phase (discovery phase, validation phase 1, validation phase 2, supplementary phase, and cohort phase) multicenter (EENT hospital, Shanghai Xuhui Central Hospital), cross-sectional, prospective cohort study designed to perform widely targeted metabolomics and chemiluminescence immunoassay to determine candidate biomarkers. Five machine learning (random forest, support vector machine, lasso, K-nearest neighbor, and GaussianNaive Bayes [NB]) approaches were used to identify an optimal algorithm. The discrimination ability was evaluated using the area under the receiver operating characteristic curve (AUC). Calibration was assessed by Hosmer-Lemeshow tests and calibration plots.
RESULTS
Studied serum samples were collected from 616 participants, and 1464 metabolites were identified. Machine learning algorithm determines that androstenedione exhibited excellent discrimination and acceptable calibration in discriminating PACG across the discovery phase (discovery set 1, AUCs=1.0 [95% CI, 1.00-1.00]; discovery set 2, AUCs = 0.85 [95% CI, 0.80-0.90]) and validation phases (internal validation, AUCs = 0.86 [95% CI, 0.81-0.91]; external validation, AUCs = 0.87 [95% CI, 0.80-0.95]). Androstenedione also exhibited a higher AUC (0.92-0.98) to discriminate the severity of PACG. In the supplemental phase, serum androstenedione levels were consistent with those in aqueous humor (r=0.82, p=0.038) and significantly (p=0.021) decreased after treatment. Further, cohort phase demonstrates that higher baseline androstenedione levels (hazard ratio = 2.71 [95% CI: 1.199-6.104], p=0.017) were associated with faster visual field progression.
CONCLUSIONS
Our study identifies serum androstenedione as a potential biomarker for diagnosing PACG and indicating visual field progression.
FUNDING
This work was supported by Youth Medical Talents - Clinical Laboratory Practitioner Program (2022-65), the National Natural Science Foundation of China (82302582), Shanghai Municipal Health Commission Project (20224Y0317), and Higher Education Industry-Academic-Research Innovation Fund of China (2023JQ006).
Topics: Humans; Androstenedione; Bayes Theorem; Biomarkers; China; Cross-Sectional Studies; Glaucoma, Angle-Closure; Prospective Studies; Visual Fields
PubMed: 38358793
DOI: 10.7554/eLife.91407 -
Journal of Mid-life Health 2023The aim of this study was to examine the association between endogenous hormones and bone mineral density (BMD) in postmenopausal women.
AIM
The aim of this study was to examine the association between endogenous hormones and bone mineral density (BMD) in postmenopausal women.
MATERIALS AND METHODS
This was a cross-sectional study of 798 postmenopausal women aged 47-85 years. Data were collected on age, age at menopause, years since menopause, smoking status, body mass index, adiposity, BMD, physical activity, and Vitamin D supplementation. Measured hormonal parameters were: follicle-stimulating hormone (FSH), estradiol, testosterone, dehydroepiandrosterone sulfate, ∆4-androstenedione, cortisol, insulin-like growth factor-1, 25-hydroxyvitamin D, and parathormone (PTH) levels. BMD was measured at the lumbar spine, femoral neck, and total hip using dual-energy X-ray absorptiometry. A directed acyclic graph was used to select potential confounding variables.
RESULTS
Multivariable analysis showed significant associations between cortisol and femoral neck BMD (β: -0.02, 95% confidence interval [CI]: -0.03--0.00), and PTH with femoral neck BMD (β: -0.01, 95% CI: -0.02--0.01) and total hip BMD (β: -0.01, 95% CI: -0.01--0.00). Hormonal factors more likely associated with a higher risk of low BMD (osteopenia or osteoporosis) were FSH (odds ratio [OR]: 1.02, 95% CI: 1.01-1.03) and PTH (OR: 1.02, 95% CI: 1.01-1.04).
CONCLUSIONS
Higher cortisol and PTH levels were inversely associated with BMD. Postmenopausal women with higher FSH or PTH levels were likely to have low BMD.
PubMed: 38312770
DOI: 10.4103/jmh.jmh_115_23