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American Journal of Men's Health Nov 2016An increasing number of men are being diagnosed with hypogonadism. While many benefit from testosterone supplementation therapy, others who do not meet the criteria for... (Review)
Review
An increasing number of men are being diagnosed with hypogonadism. While many benefit from testosterone supplementation therapy, others who do not meet the criteria for hormone supplementation have turned to dietary adjuncts as a way or gaining improvements in libido, energy, and physical performance. These oral adjunct medications include controlled substances such as androstenedione, androstenediol as well as other "over-the-counter" options like DHEA (dehydroepiandrosterone) and herbal remedies like Tribulus terrestris This review will focus on the use of these adjunct medications in isolation, or in combination with testosterone supplementation therapy as well as the biochemical nature of the supplements, the results of scientific trials as well as the side effects that limit their use. At the end of this review, physicians will have an improved understanding of the popular testosterone adjuncts being used currently as well as the availability of these substances and how they are used.
Topics: Androstenediol; Androstenedione; Dehydroepiandrosterone; Dietary Supplements; Hormone Replacement Therapy; Humans; Hypogonadism; Male; Quality of Life; Testosterone; Time Factors
PubMed: 26272885
DOI: 10.1177/1557988315598554 -
Journal of Lipid Research Sep 2015Steroids are primarily present in human fluids in their sulfated forms. Profiling of these compounds is important from both diagnostic and physiological points of view....
Steroids are primarily present in human fluids in their sulfated forms. Profiling of these compounds is important from both diagnostic and physiological points of view. Here, we present a novel method for the quantification of 11 intact steroid sulfates in human serum by LC-MS/MS. The compounds analyzed in our method, some of which are quantified for the first time in blood, include cholesterol sulfate, pregnenolone sulfate, 17-hydroxy-pregnenolone sulfate, 16-α-hydroxy-dehydroepiandrosterone sulfate, dehydroepiandrosterone sulfate, androstenediol sulfate, androsterone sulfate, epiandrosterone sulfate, testosterone sulfate, epitestosterone sulfate, and dihydrotestosterone sulfate. The assay was conceived to quantify sulfated steroids in a broad range of concentrations, requiring only 300 μl of serum. The method has been validated and its performance was studied at three quality controls, selected for each compound according to its physiological concentration. The assay showed good linearity (R(2) > 0.99) and recovery for all the compounds, with limits of quantification ranging between 1 and 80 ng/ml. Averaged intra-day and between-day precisions (coefficient of variation) and accuracies (relative errors) were below 10%. The method has been successfully applied to study the sulfated steroidome in diseases such as steroid sulfatase deficiency, proving its diagnostic value. This is, to our best knowledge, the most comprehensive method available for the quantification of sulfated steroids in human blood.
Topics: Cholesterol Esters; Chromatography, Liquid; Humans; Progestins; Sulfates; Tandem Mass Spectrometry; Testosterone Congeners
PubMed: 26239050
DOI: 10.1194/jlr.D061499 -
The Journal of Steroid Biochemistry and... Aug 2015Celecoxib has been reported to switch the human SULT2A1-catalyzed sulfonation of 17β-estradiol (17β-E2) from the 3- to the 17-position. The effects of celecoxib on the...
Celecoxib has been reported to switch the human SULT2A1-catalyzed sulfonation of 17β-estradiol (17β-E2) from the 3- to the 17-position. The effects of celecoxib on the sulfonation of selected steroids catalyzed by human SULT2A1 were assessed through in vitro and in silico studies. Celecoxib inhibited SULT2A1-catalyzed sulfonation of dehydroepiandrosterone (DHEA), androst-5-ene-3β, 17β-diol (AD), testosterone (T) and epitestosterone (Epi-T) in a concentration-dependent manner. Low μM concentrations of celecoxib strikingly enhanced the formation of the 17-sulfates of 6-dehydroestradiol (6D-E2), 17β-dihydroequilenin (17β-Eqn), 17β-dihydroequilin (17β-Eq), and 9-dehydroestradiol (9D-E2) as well as the overall rate of sulfonation. For 6D-E2, 9D-E2 and 17β-Eqn, celecoxib inhibited 3-sulfonation, however 3-sulfonation of 17β-Eq was stimulated at celecoxib concentrations below 40 μM. Ligand docking studies in silico suggest that celecoxib binds in the substrate-binding site of SULT2A1 in a manner that prohibits the usual binding of substrates but facilitates, for appropriately shaped substrates, a binding mode that favors 17-sulfonation.
Topics: Androstenediol; Binding Sites; Celecoxib; Cyclooxygenase 2 Inhibitors; Dehydroepiandrosterone; Epitestosterone; Equilin; Estradiol; Humans; Models, Molecular; Molecular Docking Simulation; Pyrazoles; Recombinant Proteins; Sulfonamides; Sulfotransferases; Testosterone
PubMed: 25960318
DOI: 10.1016/j.jsbmb.2015.05.003 -
Health Physics Jun 2015World events over the past decade have highlighted the threat of nuclear terrorism as well as an urgent need to develop radiation countermeasures for acute radiation... (Review)
Review
Medical Countermeasures for Radiation Exposure and Related Injuries: Characterization of Medicines, FDA-Approval Status and Inclusion into the Strategic National Stockpile.
World events over the past decade have highlighted the threat of nuclear terrorism as well as an urgent need to develop radiation countermeasures for acute radiation exposures and subsequent bodily injuries. An increased probability of radiological or nuclear incidents due to detonation of nuclear weapons by terrorists, sabotage of nuclear facilities, dispersal and exposure to radioactive materials, and accidents provides the basis for such enhanced radiation exposure risks for civilian populations. Although the search for suitable radiation countermeasures for radiation-associated injuries was initiated more than half a century ago, no safe and effective radiation countermeasure for the most severe of these injuries, namely acute radiation syndrome (ARS), has been approved by the United States Food and Drug Administration (FDA). The dearth of FDA-approved radiation countermeasures has prompted intensified research for a new generation of radiation countermeasures. In this communication, the authors have listed and reviewed the status of radiation countermeasures that are currently available for use, or those that might be used for exceptional nuclear/radiological contingencies, plus a limited few medicines that show early promise but still remain experimental in nature and unauthorized for human use by the FDA.
Topics: Amifostine; Androstenediol; Animals; Drug Approval; Granulocyte Colony-Stimulating Factor; Humans; Metalloporphyrins; Peptides; Radiation Injuries; Radiation-Protective Agents; Strategic Stockpile; United States; United States Food and Drug Administration
PubMed: 25905522
DOI: 10.1097/HP.0000000000000279 -
Minerva Ginecologica Dec 2013Observations over the past decade using longitudinal data reveal a gender-specific shift in adrenal steroid production. This shift is represented by an increase in the...
Observations over the past decade using longitudinal data reveal a gender-specific shift in adrenal steroid production. This shift is represented by an increase in the circulating concentrations of delta 5 steroids in 85% of all women and is initiated only after the menopausal transition has begun. While the associated rise in the major adrenal androgen, dehydroepiandrosterone sulfate (DHEAS), is modest, the parallel rises in dehydroepiandrosteone (DHEA) and androstenediol (Adiol) are much more robust. These increases in circulating steroid concentrations are qualitatively similar on average between ethnicities but quantitatively different between individual women. Both circulating testosterone (T) and androstenedione (Adione) also rise concomitantly but modestly by comparison. This phenomenon presents a new and provocative aspect to the endocrine foundations of the menopausal transition and may provide important clues to understanding the fundamentals of mid-aged women's healthy aging, particularly an explanation for the wide diversity in phenotypes observed during the MT as well as their different responses to hormone replacement therapies. Experimental studies using the nonhuman primate animal model show an acute adrenal response to human chorionic gonadotropin (hCG) challenge as well as the presence of luteinizing hormone receptors (LHR) in their adrenal cortices. These experimental results support the concept that LHRs are recruited to the adrenal cortices of mid-aged women that subsequently function to respond to increasing circulating LH to shunt pregnenolone metabolites towards the delta 5 pathway. Future investigations are required to determine the relationship of these changes in adrenal function to symptoms and health outcomes of mid-aged women.
Topics: Androgens; Animals; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Humans; Menopause; Testosterone
PubMed: 24346252
DOI: No ID Found -
Physiological Research 2014Steroids are important markers in pregnancy. Although estimating their levels separately in umbilical arterial (UA) and venous blood (UV) enable more precise insights... (Comparative Study)
Comparative Study
Steroids are important markers in pregnancy. Although estimating their levels separately in umbilical arterial (UA) and venous blood (UV) enable more precise insights into the functioning fetoplacental unit compared to using mixed umbilical blood (UM), selective aspiration of UA and UV is technically more demanding than collecting UM. We measured the levels of 67 unconjugated steroids and steroid polar conjugates in UA and UV using GC-MS in 80 women giving birth within weeks 28 to 42 of gestation. The samples were sorted into three groups: women entering labor within weeks 28-32 (group A, n=19), weeks 33-37 (group B, n=19), and weeks 38-42 (group C, n=42) of gestation, respectively. The preterm labors were due to pathologies unrelated to steroid status. Most unconjugated steroids exhibited pronounced arteriovenous differences (AVD). The AVD were less distinct in more stable steroid conjugates. Most steroids positively correlate with gestational age, but unconjugated 5beta-reduced pregnanes show negative correlations, as do testosterone and androstenediol, substrates for the placental synthesis of estrogens. Tight correlations between steroids in UA and UV indicate that steroid measurements in UA, UV and UM can be accurately derived from each other, which is important for the diagnostics of steroid related diseases in newborns.
Topics: Adult; Female; Fetal Blood; Humans; Infant, Newborn; Metabolome; Pregnancy; Premature Birth; Steroids; Umbilical Arteries; Umbilical Cord; Umbilical Veins; Young Adult
PubMed: 24182340
DOI: 10.33549/physiolres.932624 -
European Child & Adolescent Psychiatry Jun 2014Autism is diagnosed on the basis of behavioral manifestations, but its biomarkers are not well defined. A strong gender bias typifying autism (it is 4-5 times more...
Autism is diagnosed on the basis of behavioral manifestations, but its biomarkers are not well defined. A strong gender bias typifying autism (it is 4-5 times more prevalent in males) suggests involvement of steroid hormones in autism pathobiology. In order to evaluate the potential roles of such hormones in autism, we compared the salivary levels of 22 steroids in prepubertal autistic male and female children from two age groups (3-4 and 7-9 years old) with those in healthy controls. The steroids were analyzed using gas chromatography-mass spectrometry and radioimmunoassay. Statistical analysis (ANOVA) revealed that autistic children had significantly higher salivary concentrations of many steroid hormones (both C21 and C19) than control children. These anomalies were more prominent in older autistic children and in boys. The levels of androgens (androstenediol, dehydroepiandrosterone, androsterone and their polar conjugates) were especially increased, indicative of precocious adrenarche and predictive of early puberty. The concentrations of the steroid precursor, pregnenolone, and of several pregnanolones were also higher in autistic than in healthy children, but cortisol levels were not different. Some steroids, whose levels are raised in autism (allopregnanolone, androsterone, pregnenolone, dehydroepiandrosterone and their sulfate conjugates) are neuroactive and modulate GABA, glutamate, and opioid neurotransmission, affecting brain development and functioning. These steroids may contribute to autism pathobiology and symptoms such as elevated anxiety, sleep disturbances, sensory deficits, and stereotypies among others. We suggest that salivary levels of selected steroids may serve as biomarkers of autism pathology useful for monitoring the progress of therapy.
Topics: Androgens; Autistic Disorder; Biomarkers; Case-Control Studies; Child; Child, Preschool; Female; Humans; Male; Saliva
PubMed: 24043498
DOI: 10.1007/s00787-013-0472-0 -
PloS One 2013Studies relating long-term exposure to persistent organochlorine pollutants (POPs) with endocrine activities (endocrine disrupting chemicals) on circulating levels of...
BACKGROUND
Studies relating long-term exposure to persistent organochlorine pollutants (POPs) with endocrine activities (endocrine disrupting chemicals) on circulating levels of steroid hormones have been limited to a small number of hormones and reported conflicting results.
OBJECTIVE
We examined the relationship between serum concentrations of dehydroepiandrosterone, dehydroepiandrosterone sulphate, androstenedione, androstenediol, testosterone, free and bioavailable testosterone, dihydrotestosterone, estrone, estrone sulphate, estradiol, sex-hormone binding globulin, follicle-stimulating hormone, and luteinizing hormone as a function of level of exposure to three POPs known to interfere with hormone-regulated processes in different way: dichlorodiphenyl dichloroethene (DDE), polychlorinated biphenyl (PCB) congener 153, and chlordecone.
METHODS
We collected fasting, morning serum samples from 277 healthy, non obese, middle-aged men from the French West Indies. Steroid hormones were determined by gas chromatography-mass spectrometry, except for dehydroepiandrosterone sulphate, which was determined by immunological assay, as were the concentrations of sex-hormone binding globulin, follicle-stimulating hormone and luteinizing hormone. Associations were assessed by multiple linear regression analysis, controlling for confounding factors, in a backward elimination procedure, in multiple bootstrap samples.
RESULTS
DDE exposure was negatively associated to dihydrotestosterone level and positively associated to luteinizing hormone level. PCB 153 was positively associated to androstenedione and estrone levels. No association was found for chlordecone.
CONCLUSIONS
These results suggested that the endocrine response pattern, estimated by determining blood levels of steroid hormones, varies depending on the POPs studied, possibly reflecting differences in the modes of action generally attributed to these compounds. It remains to be investigated whether this response pattern is predictive of the subsequent occurrence of disease.
Topics: Aged; Environmental Pollutants; Gonadal Steroid Hormones; Humans; Hydrocarbons, Chlorinated; Male; Middle Aged; Public Health Surveillance; Risk Factors
PubMed: 23785499
DOI: 10.1371/journal.pone.0066460 -
The Journal of Steroid Biochemistry and... Nov 2013The inflammatory tissue microenvironment can be an active promoter in preneoplastic cancer lesions. Altered steroid hormone metabolism as induced by the inflammatory...
TGFβ1 alters androgenic metabolites and hydroxysteroid dehydrogenase enzyme expression in human prostate reactive stromal primary cells: Is steroid metabolism altered by prostate reactive stromal microenvironment?
The inflammatory tissue microenvironment can be an active promoter in preneoplastic cancer lesions. Altered steroid hormone metabolism as induced by the inflammatory microenvironment may contribute to epithelial cancer progression. Dehydroepiandrosterone sulfate (DHEAS) is the most abundant endogenous steroid hormone present in human serum and can be metabolized to DHEA, androgens and/or estrogens in peripheral tissues. We have previously reported that TGFβ1-induced reactive prostate stromal cells increase DHEA metabolism to active androgens and alter prostate cancer cell gene expression. While much of the focus on mechanisms of prostate cancer and steroid metabolism is in the epithelial cancer cells, this study focuses on TGFβ1-induced effects on DHEA metabolic pathways and enzymes in human prostate stromal cells. In DHEA-treated primary prostate stromal cells, TGFβ1 produced time- and dose-dependent increases in metabolism of DHEA to androstenedione and testosterone. Also TGFβ1-treated prostate stromal cells exhibited changes in the gene expression of enzymes involved in steroid metabolism including up-regulation of 3β hydroxysteroid dehydrogenase (HSD), and down-regulation of 17βHSD5, and 17βHSD2. These studies suggest that reactive prostate stroma and the inflammatory microenvironment may contribute to altered steroid metabolism and increased intratumoral androgens.
Topics: 17-Hydroxysteroid Dehydrogenases; 3-Hydroxysteroid Dehydrogenases; Androstenedione; Cell Line, Tumor; Dehydroepiandrosterone; Enzyme-Linked Immunosorbent Assay; Humans; Hydroxysteroid Dehydrogenases; Male; Prostate; Prostatic Neoplasms; Real-Time Polymerase Chain Reaction; Stromal Cells; Testosterone; Transforming Growth Factor beta1
PubMed: 23770322
DOI: 10.1016/j.jsbmb.2013.05.016 -
International Journal of Obesity (2005) Feb 2014We have previously shown that 24 young lean men (12 pairs of identical twins) subjected to a standardized 353 MJ (84 000 kcal) overfeeding protocol over 100 days...
OBJECTIVE
We have previously shown that 24 young lean men (12 pairs of identical twins) subjected to a standardized 353 MJ (84 000 kcal) overfeeding protocol over 100 days exhibited individual differences in body weight and composition gains. The mean (+s.d.) gains in fat mass (FM) and fat-free mass (FFM) were 5.4+1.9 kg and 2.7+1.5 kg for a total body energy (BE) gain of 221+75 MJ, representing 63% of the energy surplus consumed. We report here on the most important baseline correlates of these overfeeding-induced changes with the aim of identifying biomarkers of the response.
RESULTS
Baseline maximal oxygen uptake per kg body mass was negatively correlated with gains in weight, FM and BE (all P<0.05). Enzyme activities indicative of skeletal muscle oxidative potential correlated with gains in FM and BE (all P<0.05). Baseline thyroid-stimulating hormone levels in response to thyrotropin-releasing hormone stimulation correlated positively with changes in FM-to-FFM ratio (P<0.05). Plasma concentrations of androstenediol sulfate, dehydroepiandrosterone and 17-hydroxy pregnenolone were negatively correlated with gains in FM and BE (0.01
androstenediol sulfate (all P<0.05). High baseline levels of total TEM, testosterone and androstenediol sulfate were associated with lower FM gains, whereas high baseline levels of FT4 and estrone were found in low-FFM gainers.
CONCLUSION
Although none of the variables exerted individually an overwhelmingly strong influence on overfeeding-induced changes, baseline FFM, maximal oxygen uptake, muscle oxidative capacity, androgens and leptin levels were the most consistent significant biomarkers of the responsiveness to chronic overfeeding.
Topics: Adiponectin; Adipose Tissue; Adult; Basal Metabolism; Biomarkers; Blood Glucose; Body Composition; Body Mass Index; Body Weight; Energy Intake; Energy Metabolism; Glucose Tolerance Test; Humans; Insulin Resistance; Leptin; Male; Muscle, Skeletal; Overnutrition; Predictive Value of Tests; Sedentary Behavior; Twins, Monozygotic
PubMed: 23736367
DOI: 10.1038/ijo.2013.77