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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 -
Endocrine Journal Jun 2001Androstenediol (5-androsten-3beta, 17beta-diol, ADIOL) and androstenediol 3-sulfate (ADIOLS) are active metabolites of dehydroepiandrosterone (DHEA) and DHEA sulfate... (Comparative Study)
Comparative Study
Androstenediol (5-androsten-3beta, 17beta-diol, ADIOL) and androstenediol 3-sulfate (ADIOLS) are active metabolites of dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS), respectively, and have estrogenic activity and immunoregulatory function. We examined serum concentrations of ADIOL, ADIOLS, DHEA, DHEAS and pregnenolone sulfate (5-pregnen-3beta-ol-20-one sulfate, PREGS) in patients with Graves' thyrotoxicosis (male/female 9/14), hypothyroidism (11/20) and in normal controls (14/29). In hypothyroidism serum levels of all these steroids were significantly decreased in both genders. In hyperthyroidism, in contrast, serum levels of ADIOLS (male 1.49 +/- 0.69, female 0.64 +/- 0.31 micromol/l), DHEAS (male 7.43 +/- 3.91, female 5.13 +/- 2.03 micromol/l), and PREGS (male 1.13 +/- 0.58, female 1.07 +/- 0.85 micromol/l) were markedly increased, but serum concentrations of ADIOL and DEHA were not significantly different from controls (ADIOLS male 0.36 +/- 0.33, female 0.14 +/- 0.09 micromol/l; DHEAS male 2.88 +/- 1.70, female 1.86 +/- l1.03pmol/l; PREGS male 0.18 +/- 0.12, female 0.11 +/- 0.08 micromol/l; ADIOL male 3.76 +/- 1.35, female 1.91 +/- 1.17 nmol/l; DHEA male 9.23 +/- 3.49, female 13.5 +/- 10.8nmol/l). Serum concentrations of all these steroids correlated with the serum concentration of the thyroid hormones in these patients. Serum albumin and sex hormone-binding globulin concentrations were not related to these changes in the concentrations of steroids. These findings indicate that serum concentrations of ADIOLS, ADIOL, DHEAS, DHEA and PREGS were decreased in hypothyroidism, whereas serum ADIOLS, DHEAS and PREGS concentrations were increased but ADIOL and DHEA were normal in hyperthyroidism. Thyroid hormone may stimulate the synthesis of these steroids and sulfotransferase is speculated to be increased in hyperthyroidism. Increased ADIOLS might contribute to menstrual disturbances and gynecomastia in hyperthyroidism.
Topics: Adult; Androstenediol; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Female; Humans; Hyperthyroidism; Hypothyroidism; Male; Middle Aged; Pregnenolone; Sex Characteristics; Sex Hormone-Binding Globulin; Thyroxine
PubMed: 11523906
DOI: 10.1507/endocrj.48.345 -
Drug Discovery Today Feb 2024Moderate-to-high doses of ionizing irradiation can lead to potentially life-threatening morbidities and increase mortality risk. In preclinical testing, 5-androstenediol... (Review)
Review
Moderate-to-high doses of ionizing irradiation can lead to potentially life-threatening morbidities and increase mortality risk. In preclinical testing, 5-androstenediol has been shown to be effective in protecting against hematopoietic acute radiation syndrome. This agent is important for innate immunity, serves to modulate cell cycle progression, reduces radiation-induced apoptosis, and regulates DNA repair. The drug has been evaluated clinically for its pharmacokinetics and safety. The United States Food and Drug Administration granted investigational new drug status to its injectable depot formulation (NEUMUNE). Its safety and efficacy profiles make it an attractive candidate for further development as a radiation countermeasure.
Topics: United States; Humans; Acute Radiation Syndrome; Radiation-Protective Agents; Androstenediol; Immunity, Innate
PubMed: 38097137
DOI: 10.1016/j.drudis.2023.103856 -
Diabetes Jun 2022Metabolomic signatures of incident diabetes remain largely unclear for the U.S. Hispanic/Latino population, a group with high diabetes burden. We evaluated the...
Metabolomic signatures of incident diabetes remain largely unclear for the U.S. Hispanic/Latino population, a group with high diabetes burden. We evaluated the associations of 624 known serum metabolites (measured by a global, untargeted approach) with incident diabetes in a subsample (n = 2,010) of the Hispanic Community Health Study/Study of Latinos without diabetes and cardiovascular disease at baseline (2008-2011). Based on the significant metabolites associated with incident diabetes, metabolite modules were detected using topological network analysis, and their associations with incident diabetes and longitudinal changes in cardiometabolic traits were further examined. There were 224 incident cases of diabetes after an average 6 years of follow-up. After adjustment for sociodemographic, behavioral, and clinical factors, 134 metabolites were associated with incident diabetes (false discovery rate-adjusted P < 0.05). We identified 10 metabolite modules, including modules comprising previously reported diabetes-related metabolites (e.g., sphingolipids, phospholipids, branched-chain and aromatic amino acids, glycine), and 2 reflecting potentially novel metabolite groups (e.g., threonate, N-methylproline, oxalate, and tartarate in a plant food metabolite module and androstenediol sulfates in an androgenic steroid metabolite module). The plant food metabolite module and its components were associated with higher diet quality (especially higher intakes of healthy plant-based foods), lower risk of diabetes, and favorable longitudinal changes in HOMA for insulin resistance. The androgenic steroid module and its component metabolites decreased with increasing age and were associated with a higher risk of diabetes and greater increases in 2-h glucose over time. We replicated the associations of both modules with incident diabetes in a U.S. cohort of non-Hispanic Black and White adults (n = 1,754). Among U.S. Hispanic/Latino adults, we identified metabolites across various biological pathways, including those reflecting androgenic steroids and plant-derived foods, associated with incident diabetes and changes in glycemic traits, highlighting the importance of hormones and dietary intake in the pathogenesis of diabetes.
Topics: Adult; Diabetes Mellitus; Hispanic or Latino; Humans; Metabolomics; Public Health; Risk Factors; Steroids
PubMed: 35293992
DOI: 10.2337/db21-1056 -
Biomedicine & Pharmacotherapy =... Jan 2020In the present study, the therapeutic effects of 5-androstenediol on radiation-induced myeloid suppression and tissue damage in mice and the possible mechanism were...
In the present study, the therapeutic effects of 5-androstenediol on radiation-induced myeloid suppression and tissue damage in mice and the possible mechanism were explored. The mice were subjected to whole-body irradiation, and 5-androstenediol was administered subcutaneously at different times and doses. The evaluation of the survival rate showed that the administration of 5-androstenediol every three days post-irradiation was the most effective in decreasing the death of the mice. Additionally, 5-androstenediol dose-dependently reduced the death caused by 9 Gy radiation. The pharmacological mechanism was investigated by blood analysis, western blot analysis, immunofluorescence and immunohistochemistry. 5-Androstenediol significantly ameliorated myeloid suppression, as demonstrated by elevated levels of total white blood cells, including neutrophils and platelets, in the peripheral blood. By H&E staining, we found that radiation-induced myeloid suppression in the bone marrow and spleen, as well as tissue damage in the lung and colon, was significantly ameliorated by treatment with 5-androstenediol. Immunohistochemistry showed elevated phosphorylation of p65 in the bone marrow and spleen, indicating the activation of NF-κB signaling. Moreover, 5-androstenediol markedly hampered the radiation-induced activation of caspase-1 and GSDMD in the colon by decreasing the interaction between AIM2 and ASC. Taken together, our results suggest that, by promoting NF-κB signaling and inhibiting inflammasome-mediated pyroptosis, 5-androstenediol can be used as a radioprotective drug.
Topics: Anabolic Agents; Androstenediol; Animals; DNA-Binding Proteins; Dose-Response Relationship, Drug; Female; Inflammasomes; Mice; Mice, Inbred C57BL; NF-kappa B; Radiation Injuries; Radiation-Protective Agents; Signal Transduction
PubMed: 31726369
DOI: 10.1016/j.biopha.2019.109597 -
British Journal of Sports Medicine Jul 2006Anabolic steroids are synthetic derivatives of testosterone, modified to enhance its anabolic actions (promotion of protein synthesis and muscle growth). They have... (Review)
Review
BACKGROUND AND OBJECTIVES
Anabolic steroids are synthetic derivatives of testosterone, modified to enhance its anabolic actions (promotion of protein synthesis and muscle growth). They have numerous side effects, and are on the International Olympic Committee's list of banned substances. Gas chromatography-mass spectrometry allows identification and characterisation of steroids and their metabolites in the urine but may not distinguish between pharmaceutical and natural testosterone. Indirect methods to detect doping include determination of the testosterone/epitestosterone glucuronide ratio with suitable cut-off values. Direct evidence may be obtained with a method based on the determination of the carbon isotope ratio of the urinary steroids. This paper aims to give an overview of the use of anabolic-androgenic steroids in sport and methods used in anti-doping laboratories for their detection in urine, with special emphasis on doping with testosterone.
METHODS
Review of the recent literature of anabolic steroid testing, athletic use, and adverse effects of anabolic-androgenic steroids.
RESULTS
Procedures used for detection of doping with endogenous steroids are outlined. The World Anti-Doping Agency provided a guide in August 2004 to ensure that laboratories can report, in a uniform way, the presence of abnormal profiles of urinary steroids resulting from the administration of testosterone or its precursors, androstenediol, androstenedione, dehydroepiandrosterone or a testosterone metabolite, dihydrotestosterone, or a masking agent, epitestosterone.
CONCLUSIONS
Technology developed for detection of testosterone in urine samples appears suitable when the substance has been administered intramuscularly. Oral administration leads to rapid pharmacokinetics, so urine samples need to be collected in the initial hours after intake. Thus there is a need to find specific biomarkers in urine or plasma to enable detection of long term oral administration of testosterone.
Topics: Administration, Oral; Androgens; Biomarkers; Doping in Sports; Humans; Injections, Intramuscular; Substance Abuse Detection; Testosterone
PubMed: 16799097
DOI: 10.1136/bjsm.2006.027482 -
Obstetrics and Gynecology Clinics of... Sep 2011The concept that adrenal androgen production gradually declines with age has changed after analysis of longitudinal data from the Study of Women's Health Across the... (Review)
Review
The concept that adrenal androgen production gradually declines with age has changed after analysis of longitudinal data from the Study of Women's Health Across the Nation (SWAN). It is now recognized that 4 adrenal androgens rise during the menopausal transition in most women. Ethnic and individual differences in sex steroids are more apparent in circulating adrenal steroids than in either estradiol or cyclic ovarian steroid hormone profiles, particularly during the early and late perimenopause. Thus, adrenal steroid production may play a larger role in the occurrence of symptoms and the potential for healthier aging than previously recognized.
Topics: Adrenal Cortex Hormones; Adrenal Glands; Androgens; Androstenediol; Dehydroepiandrosterone Sulfate; Female; Humans; Perimenopause; Testosterone
PubMed: 21961714
DOI: 10.1016/j.ogc.2011.06.001 -
The Oncologist Apr 2007Inhibitors of steroid sulfatase are being developed as a novel therapy for hormone-dependent breast cancer in postmenopausal women. Data suggest that steroid sulfatase... (Review)
Review
Inhibitors of steroid sulfatase are being developed as a novel therapy for hormone-dependent breast cancer in postmenopausal women. Data suggest that steroid sulfatase (STS) activity is much higher than aromatase activity in breast tumors and high levels of STS mRNA expression in tumors are associated with a poor prognosis. STS hydrolyzes steroid sulfates, such as estrone sulfate and dehydroepiandrosterone sulfate (DHEAS), to estrone and DHEA, which can be converted to steroids with potent estrogenic properties, that is, estradiol and androstenediol, respectively. Several potent irreversible STS inhibitors have now been identified, including STX64 (BN83495), a tricyclic sulfamate ester. This drug recently completed the first-ever trial of this new type of therapy in postmenopausal women with estrogen receptor-positive metastatic breast cancer. STX64, tested at 5-mg and 20-mg doses, was able to almost completely block STS activity in peripheral blood lymphocytes and tumor tissues. Inhibition of STS activity was associated with significant reductions in serum concentrations of androstenediol and estrogens. Unexpectedly, serum androstenedione concentrations also decreased by up to 86%, showing that this steroid, which is the main substrate for the aromatase in postmenopausal women, is derived mainly from the peripheral conversion of DHEAS. Of eight patients who completed therapy, five showed evidence of stable disease for up to 7.0 months. This new endocrine therapy offers considerable potential for the treatment of hormone-dependent breast cancer in postmenopausal women.
Topics: Antineoplastic Agents, Hormonal; Breast Neoplasms; Clinical Trials as Topic; Enzyme Inhibitors; Female; Humans; Neoplasms, Hormone-Dependent; Steryl-Sulfatase; Sulfonic Acids
PubMed: 17470679
DOI: 10.1634/theoncologist.12-4-370 -
Fertility and Sterility Apr 2002To determine the role of adrenal androgenic hormone precursors in female sexual function. (Review)
Review
OBJECTIVE
To determine the role of adrenal androgenic hormone precursors in female sexual function.
DESIGN
A review of current literature on sexual function and the androgen precursor hormone dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS).
RESULT(S)
The C(19) steroid DHEA is both an ovarian and adrenal androgen precursor hormone, whereas DHEAS is only synthesized in the adrenal cortex. Dehydroepiandrosterone sulfate secretion begins at age 10, peaks at age 20, and then wanes. Low DHEAS levels occur in men and women with adrenal insufficiency and in the elderly. Dehydroepiandrosterone, 50 mg/d, increases DHEAS levels. In women but not men, the increased DHEAS levels facilitate additional production of downstream androgens, testosterone, dihydrotestosterone, androstenedione, and androstenediol glucuronide. With the improved female androgenic profile women with adrenal insufficiency have increased sexual thoughts and fantasies as well as an enhancement in mood and well-being. In the elderly >age 65 - DHEAS levels increase in both men and women with DHEA 50 mg/d but only in women were the higher DHEAS levels accompanied by a surge in testosterone levels and in women >age 70 increased libido and enhanced sexual satisfaction as well as a 26% diminution in bone resorption, and a 10% decrease in skin pigmentation.
CONCLUSION(S)
The female adrenal androgen deficiency syndrome, characterized low serum DHEAS levels may be corrected by DHEA supplements that increase levels of DHEAS and downstream androgens of importance to female sexuality.
Topics: Adolescent; Adrenal Glands; Adult; Age Factors; Aged; Clinical Trials as Topic; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Female; Humans; Male; Middle Aged; Sexuality
PubMed: 12007898
DOI: 10.1016/s0015-0282(02)02987-4 -
The Journal of Clinical Endocrinology... Dec 2016Adrenal production of dehydroepiandrosterone sulfate (DHEA-S) increases throughout childhood owing to expansion of the zona reticularis (ZR). ZR features cells with a...
CONTEXT
Adrenal production of dehydroepiandrosterone sulfate (DHEA-S) increases throughout childhood owing to expansion of the zona reticularis (ZR). ZR features cells with a steroidogenic phenotype distinct from that of the adjacent zona fasciculata, with higher expression of cytochrome b type A (CYB5A) and steroid sulfotransferase type 2A1 but decreased 3β-hydroxysteroid dehydrogenase type 2 (HSD3B2). In addition to DHEA-S, three adrenal Δ5-steroid sulfates could provide additional tools to define adrenal maturation.
OBJECTIVE
This study sought to simultaneously measure serum levels of four adrenal Δ5-steroid sulfates, pregnenolone sulfate (Preg-S), 17α-hydroxypregnenolone sulfate (17OHPreg-S), DHEA-S, and 5-androstenediol-3-sulfate (Adiol-S) as a function of age and relate their production to the age-dependent adrenal localization of CYB5A.
PARTICIPANTS AND METHODS
Δ5-steroid sulfates were quantified by liquid chromatography-tandem mass spectrometry in sera from 247 normal children (129 males,118 females) age 1.5-18 y and 42 adults (20 males, 22 females). Immunofluorescence localized HSD3B2 and CYB5A in normal adrenal glands from subjects age 2-35 y. Finally, HAC15 adrenocortical cells were transduced with lentiviral short hairpin RNA to suppress CYB5A expression.
RESULTS
Of the Δ5-steroid sulfates quantified, DHEA-S was most abundant. Adiol-S increased in parallel with DHEA-S. Steroid ratios (17OHPreg-S/DHEA-S) suggested increases in 17,20-lyase activity during childhood. Immunofluorescence analysis showed age-related increases in ZR CYB5A immunoreactivity. Furthermore, silencing CYB5A in HAC15 adrenocortical cells significantly reduced DHEA-S and Adiol-S production.
CONCLUSION
Adiol-S shows a similar age-related increase to that of DHEA-S. This likely results from the childhood expansion of CYB5A-expressing ZR, which enhances 17,20-lyase activity and the production of DHEA-S and Adiol-S.
Topics: 17-alpha-Hydroxypregnenolone; Adolescent; Adrenal Glands; Adult; Age Factors; Androstenediol; Cell Culture Techniques; Child; Child, Preschool; Cytochromes b5; Dehydroepiandrosterone Sulfate; Female; Human Development; Humans; Infant; Male; Pregnenolone; Progesterone Reductase; Young Adult
PubMed: 27623070
DOI: 10.1210/jc.2016-2864