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Cleveland Clinic Journal of Medicine Jan 2021
Topics: Androgens; Dehydroepiandrosterone; Female; Humans; Postmenopause; Testosterone
PubMed: 33384314
DOI: 10.3949/ccjm.88a.20195 -
Environment International Nov 2023Indoor pollutants change over time and place. Exposure to hazardous organics is associated with adverse health effects. This work sampled gaseous organics by Tenax TA...
Indoor pollutants change over time and place. Exposure to hazardous organics is associated with adverse health effects. This work sampled gaseous organics by Tenax TA tubes in two indoor rooms, i.e., an office set as samples, and the room of chassis dynamometer (RCD) set as backgrounds. Compounds are analyzed by a thermal desorption comprehensive two-dimensional gas chromatography-quadrupole mass spectrometer (TD-GC × GC-qMS). Four new chemicals of emerging concern (CECs) are screened in 469 organics quantified. We proposed a three-step pipeline for CECs screening utilizing GC × GC including 1) non-target scanning of organics with convincing molecular structures and quantification results, 2) statistical analysis between samples and backgrounds to extract useful information, and 3) pixel-based property estimation to evaluate the contamination potential of addressed chemicals. New CECs spotted in this work are all intermediate volatility organic compounds (IVOCs), containing mintketone, isolongifolene, β-funebrene, and (5α)-androstane. Mintketone and sesquiterpenes may be derived from the use of volatile chemical products (VCPs), while (5α)-androstane is probably human-emitted. The occurrence and contamination potential of the addressed new CECs are reported for the first time. Non-target scanning and the measurement of IVOCs are of vital importance to get a full glimpse of indoor organics.
Topics: Humans; Gas Chromatography-Mass Spectrometry; Mass Spectrometry; Gases; Androstanes
PubMed: 37839268
DOI: 10.1016/j.envint.2023.108259 -
Obesity (Silver Spring, Md.) Feb 2023Concerns have been raised regarding the impact of time-restricted eating (TRE) on sex hormones in females. This study examined how TRE affects sex steroids in...
OBJECTIVE
Concerns have been raised regarding the impact of time-restricted eating (TRE) on sex hormones in females. This study examined how TRE affects sex steroids in premenopausal and postmenopausal females.
METHODS
This is a secondary analysis of an 8-week TRE study (4- to 6-hour eating window) conducted in adults with obesity. Men and perimenopausal females were excluded. Females were classified into two groups based on menstrual status: premenopausal (n = 12) or postmenopausal (n = 11).
RESULTS
After 8 weeks, body weight decreased in premenopausal females (-3% ± 2%) and postmenopausal females (-4% ± 2%) (main effect of time, p < 0.001), with no difference between groups (no group × time interaction). Circulating levels of testosterone, androstenedione, and sex hormone binding globulin (SHBG) did not change in either group (no group × time interaction). Dehydroepiandrosterone (DHEA) concentrations decreased (p < 0.05) in premenopausal (-14% ± 32%) and postmenopausal females (-13% ± 34%; main effect of time, p = 0.03), with no difference between groups. Estradiol, estrone, and progesterone were measured only in postmenopausal females, and they remained unchanged.
CONCLUSIONS
In premenopausal females, androgens and SHBG remained unchanged during TRE, whereas DHEA decreased. In postmenopausal females, estrogens, progesterone, androgens, and SHBG did not change, but DHEA was reduced.
Topics: Adult; Female; Humans; Androgens; Dehydroepiandrosterone; Estradiol; Gonadal Steroid Hormones; Postmenopause; Progesterone; Sex Hormone-Binding Globulin; Testosterone; Intermittent Fasting
PubMed: 36203273
DOI: 10.1002/oby.23562 -
F1000Research 2019Late-onset hypogonadism (LOH) is the term used to describe the decline in serum testosterone levels associated with increasing age in men above 40 years. A number of... (Review)
Review
Late-onset hypogonadism (LOH) is the term used to describe the decline in serum testosterone levels associated with increasing age in men above 40 years. A number of symptoms are attributed to LOH, but the most common association is that of sexual dysfunction. LOH has recently come under greater scrutiny with the widespread use of testosterone therapy, and concerns regarding the efficacy and safety of testosterone replacement therapy have been raised. In particular, the cardiovascular safety and the beneficial effects of testosterone replacement therapy on general health have been questioned. This review will give an overview of the current evidence for the relationship of LOH and male sexual dysfunction.
Topics: Androgens; Hormone Replacement Therapy; Humans; Hypogonadism; Male; Sexual Dysfunction, Physiological; Testosterone
PubMed: 30984376
DOI: 10.12688/f1000research.16561.1 -
The Journal of Clinical Endocrinology... Mar 2022Male sex is a major risk factor for abdominal aortic aneurysms (AAA) but few studies have addressed associations between sex hormone levels and AAA.
CONTEXT
Male sex is a major risk factor for abdominal aortic aneurysms (AAA) but few studies have addressed associations between sex hormone levels and AAA.
OBJECTIVE
We aimed to describe the associations between serum sex steroids and early, screening-detected AAA in men.
METHODS
We validated a high-sensitivity liquid chromatography-tandem mass spectrometry assay for comprehensive serum sex hormone profiling. This assay was then employed in a case-control study including 147 men with AAA (infrarenal aorta ≥ 30 mm) and 251 AAA-free controls recruited at the general population-based ultrasound screening for AAA in 65-year-old Swedish men.
OUTCOMES INCLUDED
associations between dehydroepiandrosterone, progesterone, 17α-hydroxyprogesterone, androstenedione, estrone, testosterone, dihydrotestosterone, and estradiol and AAA presence.
RESULTS
Dehydroepiandrosterone, progesterone, 17α-hydroxyprogesterone, testosterone, and estradiol, but not the other hormones, were lower in men with AAA. In models with adjustments for known AAA risk factors and comorbidity, only progesterone (odds ratio per SD decrease 1.62 [95% CI, 1.18-2.22]) and estradiol (1.40 [95% CI, 1.04-1.87]) remained inversely associated with the presence of AAA. Progesterone and estradiol contributed with independent additive information for prediction of AAA presence; compared with men with high (above median) levels, men with low (below median) levels of both hormones had a 4-fold increased odds ratio for AAA (4.06 [95% CI, 2.25-7.31]).
CONCLUSION
Measured by a high-performance sex steroid assay, progesterone and estradiol are inversely associated with AAA in men, independent of known risk factors. Future studies should explore whether progesterone and estradiol, which are important reproductive hormones in women, are protective in human AAA.
Topics: Aged; Aortic Aneurysm, Abdominal; Case-Control Studies; Dehydroepiandrosterone; Dihydrotestosterone; Estradiol; Female; Humans; Male; Progesterone; Testosterone
PubMed: 34865072
DOI: 10.1210/clinem/dgab867 -
Journal of Affective Disorders Nov 2021Background Adrenal and sex hormone dysregulation have been independently associated with increased depression and anxiety. Cortisol can modify production of sex hormones...
Background Adrenal and sex hormone dysregulation have been independently associated with increased depression and anxiety. Cortisol can modify production of sex hormones and hormone-mood associations. This study evaluated associations and interplay of sex and adrenal hormones with depression and anxiety. Methods We assessed 545 Ecuadorian adolescents (11-17y, 50.4% female, ESPINA) for depression and anxiety symptoms using standardized scales. Testosterone, cortisol, dehydroepiandrosterone (DHEA), and estradiol (boys only) were measured in saliva. We performed logistic regression modeling to calculate odds ratios (OR) of elevated depression or anxiety (scores ≥60) comparing participants with low (<10th percentile) and elevated hormones (≥90th percentile) to normal concentrations (10th-90th percentile). Effect modification by cortisol and testosterone was assessed. Models adjusted for demographic, anthropometric, and circadian measures. Results In all participants, elevated testosterone (OR [95%CI:]=1.78 [0.98, 3.23]) and cortisol (OR=1.69 [0.95, 2.99]) were marginally associated with elevated anxiety scores. In boys, elevated estradiol was associated with elevated depression (OR=4.75 [1.95, 11.56]) and anxiety scores (OR=2.43 [1.01, 5.84]). In linear regression, estradiol was positively associated with depression (difference/10% hormone increase (β=0.45 [0.15, 0.75]) and anxiety scores (β=0.42 [0.13, 0.72]). Higher cortisol levels strengthened the depression association with estradiol in boys (β=0.54 [0.12, 0.96]), and with testosterone (β= -0.19 [-0.35, -0.03]) and DHEA (β= -0.12 [-0.22, -0.02]) in girls. Testosterone also modified associations. Limitations This was a cross-sectional analysis. Discussion Elevated testosterone, cortisol, and estradiol (≥90th percentile) were associated with altered mood. Cortisol and testosterone were considerable effect modifiers to the associations of most hormones with depression and anxiety.
Topics: Adolescent; Anxiety; Cross-Sectional Studies; Dehydroepiandrosterone; Depression; Estradiol; Female; Humans; Hydrocortisone; Male; Testosterone
PubMed: 34375211
DOI: 10.1016/j.jad.2021.07.026 -
Cleveland Clinic Journal of Medicine Jan 2021In women, the androgens testosterone and dehydroepiandrosterone (DHEA) play important physiologic roles in reproductive tissues, mood, cognition, the breast, bone,... (Review)
Review
In women, the androgens testosterone and dehydroepiandrosterone (DHEA) play important physiologic roles in reproductive tissues, mood, cognition, the breast, bone, muscle, vasculature, and other systems. This article reviews the effects of androgens in women, as well as the indications and best-practice recommendations for the use of androgen therapy.
Topics: Androgens; Dehydroepiandrosterone; Female; Humans; Testosterone
PubMed: 33384313
DOI: 10.3949/ccjm.88a.20030 -
Trends in Cardiovascular Medicine Apr 2015Endogenous testosterone levels are inversely associated with cardiovascular risk in older men and men with cardiovascular disease. Current data on cardiovascular... (Review)
Review
Endogenous testosterone levels are inversely associated with cardiovascular risk in older men and men with cardiovascular disease. Current data on cardiovascular outcomes of testosterone therapy include only observational studies and adverse event monitoring in short-term trials that were not designed to measure cardiovascular outcomes. These studies have yielded conflicting results, and some have raised concerns that testosterone therapy may increase cardiovascular risk. A well-designed, adequately powered, prospective trial will ultimately be required to clarify whether testosterone therapy impacts cardiovascular outcomes. This review describes the findings and limitations of recent studies of cardiovascular risk in older men on testosterone therapy and discusses some of the mechanisms through which testosterone may modify cardiovascular risk.
Topics: Adult; Cardiovascular Diseases; Cardiovascular System; Hormone Replacement Therapy; Humans; Male; Risk Factors; Testosterone
PubMed: 25467243
DOI: 10.1016/j.tcm.2014.10.014 -
Anesthesiology Feb 2023The clinical actions of sugammadex have been well studied, but the detailed molecular mechanism of the drug encapsulation process has not been systematically documented....
BACKGROUND
The clinical actions of sugammadex have been well studied, but the detailed molecular mechanism of the drug encapsulation process has not been systematically documented. The hypothesis was that sugammadex would attract rocuronium and vecuronium via interaction with the sugammadex side-chain "tentacles," as previously suggested.
METHODS
Computational molecular dynamics simulations were done to investigate docking of sugammadex with rocuronium and vecuronium. To validate these methods, strength of binding was assessed between sugammadex and a heterogeneous group of nine other drugs, the binding affinities of which have been experimentally determined. These observations hinted that high concentrations of unbound sugammadex could bind to propofol, potentially altering its pharmacokinetic profile. This was tested experimentally in in vitro cortical slices.
RESULTS
Sugammadex encapsulation of rocuronium involved a sequential progression down a series of metastable states. After initially binding beside the sugammadex molecule (mean ± SD center-of-mass distance = 1.17 ± 0.13 nm), rocuronium then moved to the opposite side to that hypothesized, where it optimally aligned with the 16 hydroxyl groups (distance, 0.82 ± 0.04 nm) before entering the sugammadex cavity to achieve energetically stable encapsulation by approximately 120 ns (distance, 0.35 ± 0.12 nm). Vecuronium formed fewer hydrogen bonds with sugammadex than did rocuronium; hence, it was less avidly bound. For the other molecules, the computational results showed good agreement with the available experimental data, showing a clear bilogarithmic relation between the relative binding free energy and the association constant (R2 = 0.98). Weaker binding was manifest by periodic unbinding. The brain slice results confirmed the presence of a weak propofol-sugammadex interaction.
CONCLUSIONS
Computational simulations demonstrate the dynamics of neuromuscular blocking drug encapsulation by sugammadex occurring from the opposite direction to that hypothesized and also how high concentrations of unbound sugammadex can potentially weakly bind to other drugs given during general anesthesia.
Topics: Sugammadex; Vecuronium Bromide; Rocuronium; gamma-Cyclodextrins; Neuromuscular Nondepolarizing Agents; Androstanols; Propofol; Dose-Response Relationship, Drug; Neuromuscular Blockade
PubMed: 36512718
DOI: 10.1097/ALN.0000000000004442 -
Autophagy Apr 2023Macroautophagy/autophagy is a multistep degradative process that is essential for maintaining cellular homeostasis and is often dysregulated during disease....
Macroautophagy/autophagy is a multistep degradative process that is essential for maintaining cellular homeostasis and is often dysregulated during disease. Systematically quantifying flux through this pathway is critical for gaining fundamental insights and effectively modulating this process. Established methods to quantify flux use steady-state measurements, which provide limited information about the perturbation and the cellular response. We present a theoretical and experimental framework to measure autophagic steps in the form of rates under non-steady-state conditions. We use this approach to measure temporal responses to rapamycin and wortmannin treatments, two commonly used autophagy modulators. We quantified changes in autophagy rates in as little as 10 min, which can establish direct mechanisms for autophagy perturbation before feedback begins. We identified concentration-dependent effects of rapamycin on the initial and temporal progression of autophagy rates. We also found variable recovery time from wortmannin's inhibition of autophagy, which is further accelerated by rapamycin. Furthermore, we applied this approach to study the effect of serum and glutamine starvation on autophagy. Serum starvation led to a rapid and transient increase in all the rates. Glutamine starvation led to a decrease in the rates on a longer timescale. In summary, this new approach enables the quantification of autophagy flux with high sensitivity and temporal resolution and facilitates a comprehensive understanding of this process.
Topics: Humans; Autophagy; Glutamine; Wortmannin; Lysosomes; Sirolimus
PubMed: 36026492
DOI: 10.1080/15548627.2022.2117515