UNASSIGNED: The association of sex-specific hormones with coronary computed tomography angiography(CCTA)-based plaque characteristics in women without cardiovascular disease is not well understood. We investigated the association of sex-specific hormones with coronary artery plaque characteristics in a contemporary multiracial cohort with no clinical coronary artery disease (CAD).
UNASSIGNED: In this cross-sectional analysis, we utilized data from 2,325 individuals with no clinical CAD from the Miami Heart (MiHeart) study. Multivariable logistic regression models were used to investigate the association of sex hormones: sex hormone binding globulin (SHBG), dehydroepiandrosterone (DHEA), free and total testosterone, estradiol, with plaque characteristics among women and men.
UNASSIGNED: Of the 1,155 women, 34.2% had any plaque and 3.4% had any high-risk plaque features (HRP) while among men (n = 1170), 63.1% had any plaque and 10.4% had HRP. Among women, estradiol and SHBG were associated with lower odds of any plaque after adjusting for age and race-ethnicity (estradiol OR per SD increase: 0.87, 95%CI: 0.76-0.98; SHBG OR per SD increase: 0.82, 95%CI: 0.72-0.93) but the significance did not persist after adjustment of cardiovascular risk factors. High free testosterone was associated with higher odds of HRP (aOR:3.48, 95%CI:1.07-11.26) but null associations for the other sex hormones with HRP, in the context of limited sample size. Among men, there were no significant associations between sex-specific hormones and plaque or HRP.
UNASSIGNED: Among young to middle-aged women with no clinical CAD, increasing estradiol and SHBG were associated with lower odds of any plaque and higher free testosterone was associated with HRP. Larger cohorts may be needed to validate this.

UNASSIGNED: Steroids play a key role in numerous physiological processes. Steroid determination is a useful tool to explore various endocrine diseases. Because of its specificity, mass spectrometry is considered to be a reference method for the determination of steroids in serum compared to radioimmunoassay. This technology could progress towards more automation for the optimal organization of clinical laboratories and ultimately for the benefit of patients.
UNASSIGNED: A fully automated ultra-high-performance liquid chromatography-tandem mass spectrometry method was developed and fully validated to determine five steroids in serum. Sample preparation was based on protein precipitation with filtration followed by online solid phase extraction. Chromatographic separation was performed using a biphenyl stationary phase.
UNASSIGNED: The method was successfully validated according to European Medicine Agency guidelines. Coefficients of variation did not exceed, respectively, 8.4% and 8.1% for intra- and inter-assay precision. Method comparison with radioimmunoassay showed a proportional bias for all compounds, except for testosterone in men. Comparison with another LC-MS/MS method demonstrated acceptable concordance for all steroids, although a small bias was observed for androstenedione.
UNASSIGNED: The novelty of this method is that it has been fully automated. Automation provides benefits in traceability and allows significant savings in cost and time.

UNASSIGNED: Preoperative diagnostic workup of adrenal tumors is based on imaging and hormone analyses, but charged with uncertainties. Steroid profiling by liquid chromatography tandem mass spectrometry (LC-MS/MS) in 24-h urine has shown potential to discriminate benign and malignant adrenal tumors. Our aim was to develop and validate a specific and accurate LC-MS/MS method for the quantification of deconjugated urinary marker steroids, to evaluate their pre-analytical stability and to apply the method to clinical samples of patients with adrenal tumors.
UNASSIGNED: A method for the quantification of 11 deconjugated steroids (5-pregnenetriol, dehydroepiandrosterone, cortisone, cortisol, α-cortolone, tetrahydro-11-deoxycortisol, etiocholanolone, pregnenolone, pregnanetriol, pregnanediol, and 5-pregnenediol) in human urine was developed and validated based on international guidelines. Steroids were enzymatically deconjugated and extracted by solid phase extraction before LC-MS/MS quantification in positive electrospray ionization mode.
UNASSIGNED: Excellent linearity with R2 > 0.99 and intra- and inter-day precisions of < 10.1 % were found. Relative matrix effects were between 96.4 % and 101.6 % and relative recovery was between 98.2 % and 115.0 %. Sufficient pre-freeze stability for all steroids in urine was found at 20-25 °C for seven days and at 4-6 °C for up to 28 days. Samples were stable during long-term storage at -20 °C and -80 °C for 6 months.
UNASSIGNED: A sensitive and robust LC-MS/MS method for the quantification of 11 urinary steroids was developed and validated according to international guidelines. Pre-analytical matrix stability was evaluated and the suitability of the method for the analysis of clinical samples and prospective validation studies was shown.

Compared with the P. longanae-infected longan, the DNP-treated P. longanae-infected fruit represented a higher pulp breakdown index, a higher O2 -. production rate, and a higher MDA content, but the lower activities of APX, SOD and CAT, the lower transcript levels of DlAPX6, DlSOD1, DlSOD2, DlSOD3 and DlCAT1, the lower values of AsA, GSH, flavonoid and total phenolics, a lower scavenging ability of DPPH radical, and a lower value of reducing power. Whereas, the ATP-treated P. longanae-infected samples showed the contrary results. The above findings indicated that the DNP-promoted the pulp breakdown in P. longanae-infected longan was because DNP weakened the capacity of scavenging ROS, raised the O2 -. level, and accelerated the membrane lipids peroxidation. However, the ATP-suppressed the pulp breakdown in P. longanae-infected longan was because ATP improved the capacity of scavenging ROS, reduced the O2 -. level, and reduced the membrane lipids peroxidation.

The expansion of the indication to use androgen deprivation therapy (ADT) to treat patients with advanced or metastatic prostate cancer has dramatically increased over the recent decades, resulting in the progress of patients\' survival. However, chronic health implications can become more apparent as the number of long-term cancer survivors is expected to be increased along with the adverse effect of ADT. In particular, interest in investigating ADT, especially luteinizing hormone-releasing hormone (LHRH) agonist association with cognitive dysfunction has been growing. Previous studies in animals and humans suggest that the level of androgen decreases with age and that cognitive decline occurs with decreases in androgen. Correspondingly, some of the extensive studies using common neurocognitive tests have shown that LHRH agonists may affect specific domains of cognitive function (e.g., visuospatial abilities and executive function). However, the results from these studies have not consistently demonstrated the association because of its intrinsic limitations. Large-scale studies based on electronic databases have also failed to show consistent results to make decisive conclusions because of its heterogeneity, complexity of covariates, and possible risk of biases. Thus, this review article summarizes key findings and discusses the results of several studies investigating the ADT association with cognitive dysfunction and risk of dementia from various perspectives.

UNASSIGNED: Variants in PAPSS2 (3\'-phosphoadenosine 5\'-phosphosulfate synthetase 2) present with varying degrees of brachyolmia (short trunk, platyspondyly, mild long-bone abnormalities). Our objective is to present the phenotype of male and female siblings with the same novel inactivating variant in PAPSS2.
UNASSIGNED: A Jordanian female (case 1), born to consanguineous parents, was referred at 10 years of age for short stature (SS). She had a normal laboratory workup, including normal growth hormone stimulation testing. Spinal x-rays done for clinical scoliosis revealed platyspondyly. She attained an adult height of 143.5 cm (-3 SD). Years later, her brother (case 2) was referred at 21 months of age for SS. His laboratory workup and bone age were normal. His growth velocity declined at 6 years of age, but normal growth factors did not suggest growth hormone deficiency. When he returned during puberty, disproportionate body measurements were noted. A skeletal survey revealed platyspondyly, increasing suspicion of growth plate pathology. Exome sequencing in the family revealed a homozygous variant, p.His496Pro (H496P) in PAPSS2 (NM_004670.3:c.1487A>C). Both parents carried the same variant.
UNASSIGNED: PAPSS2 assists with the sulfonation of dehydroepiandrosterone (DHEA) to DHEA sulfate and the sulfonation of proteoglycans in the cartilage, necessary for endochondral bone formation. PAPSS2-inactivating variants present with skeletal dysplasia and elevated DHEA levels.
UNASSIGNED: This novel variant in PAPSS2 manifested with mild brachyolmia but disproportionate SS in male and female siblings. Biochemical phenotype with low circulating DHEA sulfate and high DHEA levels reflect a sulfonation defect.

BACKGROUND: The recently identified alternate, or backdoor, pathway of DHT synthesis provides important novel information on androgen biosynthesis beyond the classical pathway. We report a rapid and versatile liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to simultaneously and accurately quantify key steroids in human or mouse serum involved in either the classical or backdoor androgen synthesis pathways.
METHODS: Serum (200 µL) fortified with isotopically labelled internal standards underwent liquid-liquid extraction (LLE) with MTBE and extracts were analysed on a LC-MS/MS. The targeted steroids for quantification were testosterone (T), dihydrotestosterone (DHT), 5α-androstane-3α,17β-diol (3α diol), 5α-androstane-3β,17β-diol (3β diol), dehydroepiandrosterone (DHEA), androstenedione (A4), androsterone (AD), estradiol (E2), estrone (E1), progesterone (P4), pregnenolone (P5), androstenediol (Adiol), 17-hydroxyprogesterone (17-OHP4) and 17-hydroxypregnenolone (17-OHP5), corticosterone (B), cortisol (F), allopregnanolone (Allo-P5) and dihydroprogesterone (DHP).
RESULTS: The limits of quantification (LOQ) were 5 pg/mL for E2 and E1, 25 pg/mL for T, 50 pg/mL for A4 and 0.10 ng/mL for DHT, 17OHP5, P4, P5, AD, Adiol, DHEA, AlloP5 and 0.20 ng/mL for 17OHP4, 3α diol, 3β diol, DHP, 0.25 ng/mL for B and 1 ng/mL for F. Accuracy, precision, reproducibility and recovery were within acceptable limits for bioanalytical method validation. The method is illustrated in human and mouse, male and female serum.
CONCLUSIONS: The presented method is sufficiently sensitive, specific and reproducible to meet the quality criteria for routine laboratory application for accurate quantitation of 18 steroid concentrations in male and female serum from humans or mice for the purpose of profiling androgen synthesis and metabolism pathways.

Although acute psychotic symptoms are often reduced by antipsychotic treatment, many patients with schizophrenia are impaired in daily functioning due to the persistence of negative and cognitive symptoms. Raloxifene, a Selective Estrogen Receptor Modulator (SERM) has been shown to be an effective adjunctive treatment in schizophrenia. Yet, there is a paucity in evidence for raloxifene efficacy in men and premenopausal women. We report the design of a study that aims to replicate earlier findings concerning the efficacy of raloxifene augmentation in reducing persisting symptoms and cognitive impairment in postmenopausal women, and to extend these findings to a male and peri/premenopausal population of patients with schizophrenia. The study is a multisite, placebo-controlled, double-blind, randomised clinical trial in approximately 110 adult men and women with schizophrenia. Participants are randomised 1:1 to adjunctive raloxifene 120 mg or placebo daily during 12 weeks. The treatment phase includes measurements at three time points (week 0, 6 and 12), followed by a follow-up period of two years. The primary outcome measure is change in symptom severity, as measured with the Positive and Negative Syndrome Scale (PANSS), and cognition, as measured with the Brief Assessment of Cognition in Schizophrenia (BACS). Secondary outcome measures include social functioning and quality of life. Genetic, hormonal and inflammatory biomarkers are measured to assess potential associations with treatment effects. If it becomes apparent that raloxifene reduces psychotic symptoms and/or improves cognition, social functioning and/or quality of life as compared to placebo, implementation of raloxifene in clinical psychiatric practice can be considered.

Androgen-secreting adrenal neoplasms have a low incidence, usually secrete multiple hormones, and may present with hirsutism, acne, and alopecia. We report an exceedingly rare case of a purely dehydroepiandrosterone-sulfate (DHEA-S) secreting adrenal neoplasm found incidentally on cross sectional imaging. The clinical, biochemical, and pathologic findings of this neoplasm are described.

The clinical management of PCOS is multifaceted but often unsatisfactory. The aim of the current study is to evaluate the effect of Vitex negundo L. in the letrozole-induced polycystic ovarian syndrome. Female Sprague-Dawley rats were divided into six groups, each containing 6 animals. Group I (Control) daily received 1% carboxymethylcellulose (CMC) suspension as a vehicle control. Letrozole (1 mg/kg) was administered per orally (p.o) for a period of 21 days for the induction of PCOS in Group II to VI. PCOS induced animals were treated with aqueous (Group III - 200 mg/kg and IV- 400 mg/kg) and hydroalcoholic extract (Group V- 200 mg/kg and VI- 400 mg/kg) of Vitex negundo up to 66 days using 0.5% w/v CMC as the vehicle. Body weight and estrous cycle phase were measured every day. Blood samples were collected on 0, 21 and 66 days for the measurement of fasting blood glucose, lipid profile, LH, FSH and hormonal level. Oral glucose tolerance test was performed to study insulin resistance effect. Toxicity markers; SGOT, SGPT, and creatinine also measured at the end of the study. The administration of Letrozole led to an abnormality in serum sex steroid profile, lipid profile, glucose and estrous cycle. It was able to successfully exert its protective effect by restoring parameters to the normal level and disappearance of cysts in ovaries. This can be attributed to phyto-components present in the extract. The aqueous and hydro-alcoholic extracts of seeds of Vitex negundo showed significant amelioration of Letrozole induced PCOS.