Steroids最新文献

{"title":"Roles of equol and the PI3K/Akt signaling pathway in the cardioprotective effects of enteral daidzein against ischemia–reperfusion injury in isolated rat hearts","authors":"Mariko Yamada ,&nbsp;Keisuke Omiya ,&nbsp;Yosuke Nakadate ,&nbsp;Takeshi Oguchi ,&nbsp;Masako Abe ,&nbsp;Akiko Kawakami ,&nbsp;Takashi Matsukawa","doi":"10.1016/j.steroids.2025.109637","DOIUrl":"10.1016/j.steroids.2025.109637","url":null,"abstract":"<div><h3>Purpose</h3><div>Daidzein, a soy-derived phytoestrogen, administered directly in the heart does not show cardioprotective effects against myocardial ischemia–reperfusion (IR) in isolated rat hearts. This study aimed to investigate whether cardioprotective effects of enteral daidzein against myocardial IR are promoted by equol, a metabolite of daidzein, through phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway.</div></div><div><h3>Methods</h3><div>Two experiments involving the Langendorff system were performed. During experiment 1, rats were divided into: daidzein group received 100 mg/kg of daidzein and control group received saline enterally 24 h before heart excision. After the rats were euthanized, blood samples were obtained to measure equol levels. Hearts were perfused with modified Krebs-Henseleit (KH) buffer before and after no-flow ischemia. During experiment 2, rats were divided into daidzein + WT (wortmannin) and control + WT groups, where daidzein (100 mg/kg) or saline (control + WT) was administered enterally 24 h before heart excision. To assess the role of the PI3K/Akt signaling pathway, an inhibitor of PI3K (wortmannin) was administered before and after no-flow ischemia in both groups. The primary outcome was the maximum left ventricular pressure derivative (LV dP/dt max) after reperfusion.</div></div><div><h3>Results</h3><div>LV dP/dt max values of the daidzein group at 10, 15, and 20 min after reperfusion were significantly higher than those of the control group (<em>P</em> &lt; 0.05). This effect was diminished by wortmannin. Enteral daidzein significantly increased serum equol levels (daidzein group: 541.5 ± 330.8 nmol/L; control group: 140.6 ± 43.3 nmol/L; <em>P</em> = 0.0043).</div></div><div><h3>Conclusion</h3><div>Enteral daidzein exhibited cardioprotective effects via PI3K/Akt signaling pathway activation, probably induced by increased serum equol level.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"220 ","pages":"Article 109637"},"PeriodicalIF":2.1,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144125250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ursane hybrids with 5-amino-1,2,3,4-thiatriazole, 1-tetrazole-5-thione, and 1-tetrazole-5-amines and study of their inhibition of main SARS-CoV-2 protease","authors":"Sergey A. Popov ,&nbsp;Elvira E. Shults ,&nbsp;Dmitry S. Baev ,&nbsp;Varvara Yu. Chirkova ,&nbsp;Ekaterina A. Volosnikova ,&nbsp;Svetlana V. Belenkaya ,&nbsp;Dmitry N. Shcherbakov ,&nbsp;Mikhail.A. Pokrovsky ,&nbsp;Mohammad S. Hamad ,&nbsp;Andrey G. Pokrovsky","doi":"10.1016/j.steroids.2025.109638","DOIUrl":"10.1016/j.steroids.2025.109638","url":null,"abstract":"<div><div>A series of new heterocyclic ursane and 28-norursane hybrids − derivatives of 5-amino-1,2,3,4-thiatriazole, 1-tetrazole–5-thione, and 1-tetrazole–5-amines were prepared. Reacting triterpenoids holding <img>N<img>C<img>S groups at different distances from the pentacyclic backbone with hydrazine hydrate resulted in ursane-derived hydrazinecarbothioamides. Subsequent nitrosation afforded terpenoid derivatives of 5-amino-1,2,3,4-thiatriazole. Heterocyclization of amino-thioureas with 3β-acetoxyurs-12-en-28-yl substituent under the action of Hg(OAc)₂-NaN₃ led to hybrids of 1-tetrazole–5-amines. 1-Tetrazole–5-thiones with different positions of heterocycle relative to the triterpene skeleton were prepared by coupling sodium azide with triterpene isothiocyanates. The activity of the new heterocyclic derivatives as inhibitors of 3CLpro of SARS-CoV-2 was investigated. Remarkable inhibition was observed for the 1-tetrazole-5-thione hybrids of triterpenoids. The highest activity among the studied compounds was provided by the combination of a 1-tetrazole-5-thione moiety at the C(28)H₂ group of the ursane frame having a free OH group at the 3-position. Molecular docking assumed the covalent binding of 3CLpro via the formation of a disulfide bond between the thiol groups of the catalytic Cys145 and the tetrazole heterocycle of the new hybrid compounds. The triterpenoid backbone provided multiple external hydrophobic contacts essential for the stability of the complex. The results demonstrate the potential of heterocyclic thione hybrids as non-peptidomimetic covalent inhibitors targeting 3CLpro protease (3-Chymotrypsin-like Protease).</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"220 ","pages":"Article 109638"},"PeriodicalIF":2.1,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144133110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New secondary metabolites from the soil-derived Aspergillus versicolor QC812","authors":"Jiacheng Weng ,&nbsp;Siqi Li ,&nbsp;Runchao Ma,&nbsp;Qi Shi,&nbsp;Xiongyu Meng,&nbsp;Guifen Zhou,&nbsp;Luping Qin,&nbsp;Huaqiang Li","doi":"10.1016/j.steroids.2025.109629","DOIUrl":"10.1016/j.steroids.2025.109629","url":null,"abstract":"<div><div>A new 18,22-cyclosterol, aspersteroline A (<strong>1</strong>), and a new DMOA-derived meroterpenoid, asperterpene O (<strong>2</strong>), along with three known compounds (<strong>3</strong> − <strong>5</strong>), namely <em>mer</em>-NF8054X (<strong>3</strong>), terretonin D (<strong>4</strong>), and asperterpene J (<strong>5</strong>), were isolated from the soil-derived <em>Aspergillus versicolor</em> QC812. The structures of new compounds were established based on widespread spectrographic methods, mainly including 1D &amp; 2D NMR and HRESIMS analyses, and the absolute configurations were further confirmed by comparison of calculated and experimental electronic circular dichroism (ECD) curves. The cytotoxicity of isolates was evaluated on five human tumor cell lines, <strong>1</strong> and <strong>3</strong> showed moderate cytotoxic activities against HL-60.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"220 ","pages":"Article 109629"},"PeriodicalIF":2.1,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144115649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sarcococca species: A source of bioactive steroidal alkaloids – A review","authors":"Nguyen Manh Ha ,&nbsp;Ninh The Son","doi":"10.1016/j.steroids.2025.109630","DOIUrl":"10.1016/j.steroids.2025.109630","url":null,"abstract":"<div><h3>Background</h3><div><em>Sarcococca</em> species (the family Buxaceae), containing a large number of steroidal alkaloids, were often used as medicinal plants for treating various ailments, such as fever, pain, and inflammation.</div></div><div><h3>Objective</h3><div>The current study aims to highlight the natural observation and pharmacological actions of <em>Sarcococca</em> steroidal alkaloids and related compounds.</div></div><div><h3>Methods</h3><div>Scientific literature of phytochemical studies and pharmacological examinations of <em>Sarcococca</em> species were collected from four main sources: Google Scholar, Web of Science, PubMed, and journal websites. “<em>Sarcococca</em>” and “steroidal alkaloids” were the primary keywords to search for references. The study covers almost all English publications from the 1960 s to the present. ChemDraw Ultra 12.0 was used to draw chemical structures of phytochemicals.</div></div><div><h3>Results</h3><div>Phytochemical results indicated that about 170 secondary metabolites have been detected in <em>Sarcococca</em>, of which 144 compounds (84.7%) can be classified as steroidal alkaloids. Other classes included sterols, triterpenoids, flavonoids, and <em>mono</em>-phenols. <em>Sarcococca</em> crude plant extracts, fractions, and their steroidal alkaloid isolates have pharmacological properties, such as cytotoxic, antimicrobial, antioxidative, antiinflammatory, antileishmanial, antiplasmodial, and antidiabetic activities. They were also recorded to protect against harmful conditions to the neurons, liver, and gastrointestinal system, and exert vasorelaxant, analgesic, estrogen biosynthesis, and nematicidal activities. Some steroidal alkaloids are better than the standard drugs to inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. Generally, substituted groups at nitrogenous atoms might be attributed to the differences in pharmacological results.</div></div><div><h3>Conclusion</h3><div>Advances in chromatographic isolations of steroidal alkaloids to obtain huge amounts are necessary. <em>In vivo</em> biological experiences and clinical testing are encouraged.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"220 ","pages":"Article 109630"},"PeriodicalIF":2.1,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144071821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In silico analysis of Moringaceae derived potential drug-like compounds against Newcastle disease virus","authors":"Muhammad Hammad Mustafa ,&nbsp;Fayyaz-ur Rehman ,&nbsp;Muhammad Ali ,&nbsp;Mohsin Javed ,&nbsp;Nazir Ahmad ,&nbsp;Tayyaba Shafique ,&nbsp;Ammar Zidan ,&nbsp;Ali Bahadur ,&nbsp;Shahid Iqbal ,&nbsp;Sajid Mahmood ,&nbsp;Abd-ElAziem Farouk ,&nbsp;Ibrahim Jafri","doi":"10.1016/j.steroids.2025.109628","DOIUrl":"10.1016/j.steroids.2025.109628","url":null,"abstract":"<div><div>Newcastle disease virus (NDV) classified in the <em>Avian avulavirus 1</em> [genus <em>Orthoavulavirus</em>, subfamily <em>Avulavirinae</em>, family <em>Paramyxoviridae</em>] constitutes a serious financial risk to the global poultry market. Available vaccines do not show good results in catering to the virus. Currently there is no FDA-approved drug to treat the disease. Nucleoprotein (NP) is a structural protein playing that constitutes a serious financial risk to the global poultry market.a valuable role in the virus replication process and encapsidation. This study is an effort to screen phytochemicals, from the plant family Moringaceae, as potential inhibitors of the N protein. ADMET (adsorption, distribution, metabolism, excretion and toxicity) analysis was performed to screen potential phytochemicals with drug likeliness. Molecular Docking was performed for the binding affinities. Gas Chromatography-Mass Spectrometry (GC–MS) and Density Function Theory (DFT) were performed to evaluate the phytochemicals bioavailability and reactivity, respectively. The stability of protein–ligand complexes was examined by 50 ns MD simulations and MM/PBSA values were calculated. Out of 128 phytochemicals, 22 phytochemicals were selected following ADMET screening. Based on the binding energies and the number of H bonding the following 10 phytochemicals were suggested as potential inhibitors to N protein of NDV – <em>cis</em>-11,14-eicosadienoic acid methyl ester, aurantiamide acetate, α-tocopherol, 4,8,12,16-tetramethylheptadecan-4-olide, 3,7,11,15-tetramethyl-2-hexadecen-1-ol, β-amyrin, β-sitosterol-3-O-β-<span>d</span>-galactopyranoside, α-amyrin, pterygospermin and sitogluside. Furthermore, DFT results showed that the 4 pytochemicals – <em>Cis</em>-11,14-eicosadienoic acid methyl ester, aurantiamide acetate, α-tocopherol, and 3,7,11,15-tetramethyl-2-hexadecen-1-ol were most reactive and thus could be used as potential inhibitors of NDV N protein. Further studies are required to validate the selected four phytochemicals as drug candidates against NDV.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"219 ","pages":"Article 109628"},"PeriodicalIF":2.1,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143935691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Palladium-catalyzed cross-coupling reactions of estrone","authors":"Peter Langer","doi":"10.1016/j.steroids.2025.109627","DOIUrl":"10.1016/j.steroids.2025.109627","url":null,"abstract":"<div><div>Palladium catalyzed cross-coupling reactions of estrone allow for the synthesis of a variety of substituted steroids which are not readily available by other methods. Products include various alkynylated and arylated estrones and 13α-estrones, 16-arylmethylidene-3-<em>O</em>-methylestrones and 16-alkynylmethylidene-3-<em>O</em>-methylestrones. Reactions usually proceed with excellent chemo- and regioselectivity and exhibit a broad functional group tolerance. In several cases, the estrone derivatives prepared proved to be active and selective inhibitors of alkaline phosphatases or exhibited considerable antiproliferative activities.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"219 ","pages":"Article 109627"},"PeriodicalIF":2.1,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143916438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Steroid sulfatase and the transporter of sulfated steroids are upregulated in granulose cells from women of POSEIDON group 4 in controlled ovarian hyperstimulation for in vitro fertilization cycles","authors":"Karina Sequeira ,&nbsp;Soledad Henríquez ,&nbsp;Paulina Kohen ,&nbsp;Ariel Fuentes ,&nbsp;Alejandro Tapia-Pizarro ,&nbsp;Pablo Céspedes ,&nbsp;Ana Godoy ,&nbsp;Luigi Devoto","doi":"10.1016/j.steroids.2025.109626","DOIUrl":"10.1016/j.steroids.2025.109626","url":null,"abstract":"<div><h3>Purpose</h3><div>The reduced circulating levels of dehydroepiandrosterone sulphate (DHEA-S) are associated with women with poor ovarian response, &gt; 35 years old and low ovarian reserve (POSEIDON group 4, PG4) in cycles of controlled ovarian hyperstimulation. In the ovary, the uptake of DHEA-S is facilitated by the transmembrane organic anion-transporting polypeptide, OATP2B1, whereas in the cytoplasm, the hydrolysis of the inactive precursor DHEA-S into the biologically active steroid DHEA is catalyzed by the steroid sulfatase enzyme (STS). The objective of the present study was to evaluate DHEA and DHEA-S in serum and follicular fluid as well as the expression levels for STS and OATP2B1 in granulosa cells from women in PG4 compared to a control group (control) of age matched women with normal ovarian reserve and response to controlled ovarian hyperstimulation.</div></div><div><h3>Methods</h3><div>Prospective study which included 23 women who underwent in vitro fertilization. We compared women in PG4 (n = 13) with a control (n = 8). Transcript levels and the cellular distribution of STS and OATP2B1 transporter were determined by qPCR and immunofluorescence respectively in granulosa cells collected at the time of oocyte pick-up. Gene expression was analyzed according to age, circulating AMH, antral follicle count (AFC) along with DHEA-S and DHEA in serum and follicular fluid.</div></div><div><h3>Results</h3><div>Serum and follicular fluid analysis showed that DHEA-S was significantly decreased in PG4 compared to control, whereas no differences in DHEA concentrations were observed. Women in PG4 had significantly higher expression of STS and OATP2B1 mRNA (n = 13, p &lt; 0.05) compared with those of the control.</div></div><div><h3>Conclusion</h3><div>Our results suggest that up-regulation of STS and OATP2B1 in granulosa cells from women in PG4 could be a compensatory mechanism to overcome the decreased circulating levels of DHEA-S possibly required as substrate for intraovarian production of DHEA.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"219 ","pages":"Article 109626"},"PeriodicalIF":2.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143912795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of dexamethasone on biological properties and metabolic adaptations of normal prostate epithelial cells under mild serum conditions","authors":"Weronika Broszkiewicz,&nbsp;Jakub Beda,&nbsp;Kamila Domińska","doi":"10.1016/j.steroids.2025.109625","DOIUrl":"10.1016/j.steroids.2025.109625","url":null,"abstract":"<div><div>Limiting serum concentration in culture medium constitutes an environmental stress that disrupts cellular homeostasis and activates adaptive metabolism. This study aims to examine the impact of dexamethasone (DEX) on biological properties (e.g. viability, adhesion, migration) and glucose and lipid metabolism of prostate epithelial cells under stress conditions. The study used a non-tumorigenic human prostate cell line, PNT1A. In mild serum deprivation conditions, DEX, commonly used in the treatment of castration-resistant prostate cancer, also arrests normal prostate cells in the G0/G1 phase. Observed reduction in metabolic activity and limiting apoptosis of PNT1A cells as related to decreased expression of the NF-κB family and <em>FOXO3</em> genes. Moreover, DEX modulated PNT1A migration by regulating cell plasticity thought capacity of adhesion to ECM proteins such as fibronectin and collagen I and IV. This was associated with changes in mRNA levels for the genes <em>VIM</em>, <em>ZEB1</em> and <em>ZEB2</em>. Finally, it seems that dexamethasone helps PNT1A cells adapt to stress and enhance antioxidant defense, possibly by reprogramming lipid metabolism (e.g., <em>LDLR</em>, <em>CPT1</em>, <em>MGLL</em>), but not necessarily glucose metabolism.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"219 ","pages":"Article 109625"},"PeriodicalIF":2.1,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143912798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dehydroepiandrosterone sulphate (DHEAS) supplementation impacts adrenal cortex morphophysiology of aged female gerbils","authors":"Carolina Marques Bedolo ,&nbsp;Isabella Carolina Cozim ,&nbsp;Vitor Grigio ,&nbsp;Gabriel Ribeiro Bernussi ,&nbsp;Stella Bicalho Silva ,&nbsp;Luiz Henrique Alves Guerra ,&nbsp;Silvana Gisele Pegorin Campos ,&nbsp;Patricia Simone Leite Vilamaior ,&nbsp;Ellen Cristina Rivas Leonel ,&nbsp;Sebastião Roberto Taboga","doi":"10.1016/j.steroids.2025.109618","DOIUrl":"10.1016/j.steroids.2025.109618","url":null,"abstract":"<div><div>During the process of aging, it is common for women to take dehydroepiandrosterone sulphate (DHEAS) supplements to prevent adrenopause. However, the potential effects of this supplementation on the adrenal cortex have not yet been fully elucidated. Therefore, the present study aimed to analyze the effects of DHEAS supplementation on the adrenal cortex of female Mongolian gerbils during the aging process. The experiment was conducted by dividing the aged female gerbils (18 months of age) into two groups (n = 5). The control group received no treatment, while the experimental group received 60 mg/kg of DHEAS for 5 weeks. The adrenal glands of both groups were then subjected to morphological, hormonal and immunohistochemistry analyses. The results showed that DHEAS supplementation led to a significant increase in the accumulation of lipofuscin granules in the adrenal cells. Furthermore, decreases in ERα and ERβ and the enzymes CYP17 and 17βHSD, and an increase in the 5α-reductase enzyme in the adrenal cortex were also observed. The results suggest that DHEAS supplementation has a negative feedback effect on the adrenal cortex, affecting its morphophysiology and, consequently, the gland’s functionality. In addition, DHEAS supplementation does not reverse all aspects of the effects of aging on adrenal gland homeostasis.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"218 ","pages":"Article 109618"},"PeriodicalIF":2.1,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143867803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mendelian randomization studies of testosterone exposure: A systematic review","authors":"Annika Magdalena Rhomberg-Kauert ,&nbsp;Morten Tulstrup ,&nbsp;Christoffer Badsted ,&nbsp;Henrik Horwitz ,&nbsp;Ida M. Heerfordt","doi":"10.1016/j.steroids.2025.109615","DOIUrl":"10.1016/j.steroids.2025.109615","url":null,"abstract":"<div><h3>Background</h3><div>Testosterone impacts reproductive health, cardiovascular function, and metabolism. Considering the use of testosterone therapy and anabolic steroid misuse, understanding its health effects is important. While randomized clinical trials provide short-term insights, and observational studies struggle with confounding factors, Mendelian randomization offers an alternative by using genetic variations to explore causal relationships.</div></div><div><h3>Method</h3><div>A systematic search was performed using MEDLINE to identify studies published from inception to October 2024. We included studies that conducted a Mendelian randomization analysis to evaluate associations between testosterone exposure and any health outcomes in males.</div></div><div><h3>Results</h3><div>Twenty-nine Mendelian randomization studies were included, examining a broad spectrum of health outcomes linked to testosterone exposure. Cardiovascular and metabolic health, alongside prostate cancer risk, were the most frequently studied areas. Most studies indicated that higher testosterone levels were associated with adverse cardiovascular outcomes, such as increased risks of thromboembolism, ischemic heart disease, and heart failure. Elevated levels of genetically predicted free testosterone consistently showed a correlation with increased prostate cancer risk. The relationship between testosterone and type 2 diabetes remained inconclusive. Neuropsychiatric and musculoskeletal outcomes received less attention, while dermatological, infectious, and respiratory health were minimally explored.</div></div><div><h3>Conclusion</h3><div>This review provides information about the causal relationships between testosterone exposure and health outcomes, contributing to the ongoing discourse on testosterone-related health risks and benefits. The included studies exhibit great heterogeneity.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"218 ","pages":"Article 109615"},"PeriodicalIF":2.1,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143834813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}