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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 -
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 -
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 -
Journal of the Endocrine Society Jul 2022Fasting is stressful for the human body. It is managed by metabolic adaptations maintaining energy homeostasis and involves steroid hormone biosynthesis, but the exact...
CONTEXT
Fasting is stressful for the human body. It is managed by metabolic adaptations maintaining energy homeostasis and involves steroid hormone biosynthesis, but the exact interplay between energy and steroid metabolism remains elusive. Women with polycystic ovary syndrome (PCOS) suffer from disturbed metabolism and androgen excess, while in women with anorexia nervosa, cortisol and androgen production are decreased. By contrast, starvation of steroidogenic cells shifts adrenal steroid biosynthesis toward enhanced androgen production.
AIM
This study investigated the effect of fasting on steroid production in healthy women.
METHODS
Twenty healthy young women fasted for 48 hours; steroid profiles from plasma and urine samples were assessed at baseline, after 24 hours, and 48 hours by liquid and gas chromatography-mass spectrometry.
RESULTS
Fasting did not change overall steroidogenesis, although it increased progestogen production and lowered relative mineralocorticoid, glucocorticoid, and androgen production. The largest decrease in urine metabolites was seen for β-cortol, dehydroepiandrosterone, and androstenediol; higher levels were found for pregnanediol in urine and progesterone and aldosterone in serum. Activity of 17α-hydroxylase/17,20-lyase (CYP17A1), essential for androgen biosynthesis, was decreased after fasting in healthy women as were 21-hydroxylase (CYP21A2) and 5α-reductase activities. By contrast, hydroxysteroid 11-beta dehydrogenase 1 (HSD11B1) activity for cortisol inactivation seemed to increase with fasting.
CONCLUSION
Significant changes in steroid metabolism occurred after 48 hours of fasting in healthy women. In contrast to metabolic changes seen at baseline in PCOS women compared to healthy women, and after starving of steroidogenic cells, no androgen excess was observed after short-term fasting in healthy young women.
PubMed: 35668998
DOI: 10.1210/jendso/bvac075 -
Expert Review of Clinical Immunology Sep 2017Sepsis is a disease process characterized by an extreme inflammatory response followed by a period of severe immunosuppression. In recent years, there has been improved... (Review)
Review
Sepsis is a disease process characterized by an extreme inflammatory response followed by a period of severe immunosuppression. In recent years, there has been improved survival in the initial immune response during systemic inflammatory response syndrome, and compensatory anti-inflammatory response, yet is mostly unchanged with 18-30% mortality during the later stage of sepsis despite numerous Phase 3 clinical trials. Areas covered: This review article presents a critical evaluation of the most promising newer studies aimed at improving the immunosuppressive stage of sepsis. Administration of DHEA/AED/AET show promise in improving survival. Blockade of signaling pathways for PD-1/PD-L1/CTLA-4, and partial blockade of TREM-1 signaling, and modification to sTREM-1 and the JAK/STAT pathway are promising methods of restoring host immune response and improving survival. While there has been significant progress, currently no findings have been translated into effective clinical interventions. Expert commentary: Clinical success by immunomodulation with individual immune mediator is encouraging and should progress to evaluating combined methods of immunoregulation. Since most of the animal studies do not reproduce human sepsis, development of better animal models and moving toward human studies for intervention will lead to the most beneficial findings in translational science.
Topics: Animals; Antibodies, Monoclonal; CTLA-4 Antigen; Clinical Trials as Topic; Disease Models, Animal; Drug Therapy, Combination; Humans; Immunomodulation; Immunotherapy; Janus Kinases; Molecular Targeted Therapy; Programmed Cell Death 1 Receptor; STAT Transcription Factors; Sepsis; Signal Transduction; Steroids; Triggering Receptor Expressed on Myeloid Cells-1
PubMed: 28742984
DOI: 10.1080/1744666X.2017.1357469 -
BMC Women's Health May 2023Associations of luteinizing hormone (LH) with androgens during the menopausal transition and associations between follicle-stimulating hormone (FSH) levels and various...
INTRODUCTION
Associations of luteinizing hormone (LH) with androgens during the menopausal transition and associations between follicle-stimulating hormone (FSH) levels and various diseases related to reproductive hormones in postmenopause have received much attention. LH and FSH are also known to be associated with activities of enzymes related to reproductive hormones. We examined the associations of LH and FSH with androgens and estrogens in each stage of the menopausal transition according to a classification from menopausal transition to postmenopause.
METHODS
This study was a cross-sectional design. We basically used the Stage of Reproductive Aging Workshop (STRAW) + 10. We divided the 173 subjects into 6 groups according to menstrual regularity and follicle-stimulating hormone level: mid reproductive stage (Group A), late reproductive stage (Group B), early menopausal transition (Group C), late menopausal transition (Group D), very early postmenopause (Group E) and early postmenopause (Group F). Levels of LH, FSH, dehydroepiandrosterone sulfate (DHEAS), estradiol, estrone, testosterone (T), free T, androstenedione and androstenediol were measured.
RESULTS
In Group A, LH showed significant positive correlations with androstenedione and estrone. In Group D, LH was positively associated with T and free T and was negatively associated with estradiol. In Groups B, C, D and F, LH showed significant positive correlations with FSH, and there was a tendency for an association between LH and FSH in Group E. FSH was associated with estradiol but not with estrone in Groups C and D.
CONCLUSION
The associations of LH and FSH with reproductive hormones are different depending on the stage of the menopausal transition.
TRIAL REGISTRATION
Trial registration number 2356-1; Date of registration: 18/02/2018, retrospectively registered.
Topics: Female; Humans; Androstenedione; Estrone; Follicle Stimulating Hormone; Cross-Sectional Studies; Luteinizing Hormone; Menopause; Estradiol; Androgens; Testosterone
PubMed: 37231423
DOI: 10.1186/s12905-023-02438-5 -
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 -
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 -
Animal : An International Journal of... Feb 2021Optimal management of gilt reproduction requires oestrus synchronization. Hormonal treatments are used for this purpose, but there is a growing demand for non-hormonal...
Optimal management of gilt reproduction requires oestrus synchronization. Hormonal treatments are used for this purpose, but there is a growing demand for non-hormonal alternatives, especially in organic farms. The boar effect is an important alternative opportunity to induce and synchronize oestrus without hormones. Before puberty, gilts exhibit a 'waiting period' during which boar exposure could induce and synchronize the first ovulation. We searched for salivary biomarkers of this period of boar effect receptivity to improve detection of the gilts to stimulate with the perspective of enhancing the efficacy of the boar effect. Saliva samples were collected from 30 Large-White×Landrace crossbred gilts between 140 and 175 days of age. Gilts were exposed twice a day to a boar and subjected to oestrus detection from 150 to 175 days of age. Among the 30 gilts, 10 were detected in oestrus 4 to 7 days after the first introduction of the boar and were considered receptive to the boar effect, 14 were detected in oestrus more than 8 days after first boar contact, and six did not show oestrus and were considered non-receptive. Saliva samples from six receptive and six non-receptive gilts were analyzed for steroidome and for metabolome using gas chromatography coupled to tandem mass spectrometry and H nuclear magnetic resonance spectroscopy, respectively. Four saliva samples per gilt were analyzed: 25 days and 11 days before boar introduction, the day of boar introduction, 3 days later for receptive gilts or 7 days later for non-receptive gilts. Twenty-nine steroids and 31 metabolites were detected in gilt saliva. Salivary concentrations of six steroids and three metabolites were significantly different between receptive and non-receptive gilts: progesterone and glycolate 25 days before boar introduction, 3α5β20α- and 3β5α20β-hexahydroprogesterone, dehydroepiandrosterone, androstenediol, succinate, and butyrate 11 days before boar introduction, and 3β5α-tetrahydroprogesterone on the day of boar introduction. Thus, nine potential salivary biomarkers of boar effect receptivity were identified in our experimental conditions. Further studies with higher numbers of gilts and salivary sampling points are necessary to ascertain their reliability.
Topics: Animals; Biomarkers; Female; Gas Chromatography-Mass Spectrometry; Male; Metabolome; Reproducibility of Results; Saliva; Sexual Maturation; Swine
PubMed: 33573980
DOI: 10.1016/j.animal.2020.100095 -
Andrology Jan 2021Previous studies on gonadal steroidogenesis have not compared metabolic pathways between fetal and adult mouse testes to date. (Comparative Study)
Comparative Study
BACKGROUND
Previous studies on gonadal steroidogenesis have not compared metabolic pathways between fetal and adult mouse testes to date.
OBJECTIVES
To evaluate comparative metabolic signatures of testicular steroids between fetus and adult mice using gas chromatography-mass spectrometry (GC-MS)-based steroid profiling.
MATERIALS AND METHODS
GC-MS with molecular-specific scan modes was optimized for selective and sensitive detection of 23 androgens, 7 estrogens, 14 progestogens, and 13 corticoids from mouse testes with a quantification limit of 0.1-5.0 ng/mL and reproducibility (coefficient of variation: 0.3%-19.9%). Based on 26 steroids quantitatively detected in testes, comparative steroid signatures were analyzed for mouse testes of 8 fetuses on embryonic day 16.5 and 8 adults on postnatal days 56-60.
RESULTS
In contrast to large amounts of steroids in adult testes (P < .0002), all testicular levels per weight unit of protein were significantly increased in fetal testes (P < .002, except 6β-hydroxytestosterone of P = .065). Both 11β-hydroxyandrostenedione and 7α-hydroxytestosterone were only measurable in fetal testes, and metabolic ratios of testosterone to androstenediol and androstenedione were also increased in fetal testes (P < .05 for both).
DISCUSSION AND CONCLUSION
Testicular steroid signatures showed that both steroidogenic Δ and Δ pathways in the production of testosterone were activated more during prenatal development. Both 7α- and 11β-hydroxylations were predominant, while hydroxylations at C-6, C-15, and C-16 of testosterone and androstenedione were decreased in the fetus. The present GC-MS-based steroid profiling may facilitate understanding of the development of testicular steroidogenesis.
Topics: Animals; Fetus; Gas Chromatography-Mass Spectrometry; Gonadal Steroid Hormones; Male; Mice; Testis
PubMed: 32810374
DOI: 10.1111/andr.12893