The effect of pretreatment transdermal testosterone gel on in vitro fertilization outcomes in patients with poor ovarian reserve, a randomized controlled trial

开始日期2025-05-01

申办/合作机构-

NCT06733350

/ Recruiting临床4期IIT

Investigating the Effect of Testosterone Replacement Therapy Among Hypogonadal Men With Localized Prostate Cancer on Active Surveillance

This phase IV trial studies the effects of testosterone replacement therapy (TRT) on treatment outcomes in hypogonadal men with prostate cancer that has not spread to other parts of the body (localized) and who are on active surveillance (AS). AS in prostate cancer involves closely watching the patient's condition through regular physical exams and blood tests, but not giving treatment unless there are changes in test results. It can be a practical alternative to treatment in localized prostate cancer. Hypogonadal men have low testosterone associated with symptoms such as low libido and erectile problems. TRT can be used to treat hypogonadism by increasing testosterone levels, which may improve associated symptoms. TRT is often not used in men with prostate cancer due to concerns it may lead to the cancer growing or spreading. This may lead hypogonadal men to have a poor quality of life or to discontinue AS. TRT may improve treatment and quality of life outcomes in hypogonadal men with localized prostate cancer on active surveillance.

开始日期2025-01-15

申办/合作机构

Roswell Park Comprehensive Cancer Center

NCT06670053

/ RecruitingN/AIIT

Effect of Testosterone on Brain Imaging and Headache in Transmasculine Adolescents

Transmasculine youth (female sex assigned at birth, male gender identity) who begin clinical gender affirming hormone therapy (GAHT) with testosterone (T) may experience changes in headache. Researchers think this because studies published on effects of giving testosterone to cisgender females (female sex, female gender identity) and transmasculine adults seem to show an effect on pain.
This research will help us learn more about changes in headache and in brain structure and function in transmasculine youth during the first two years of T. Youth who will be starting T within 6 months, either on puberty blocker or not, as part of their regular medical care can participate and will be asked to attend 4 visits:
* before starting T
* after 6 months on T
* after 1 year on T
* after 2 years on T
At the visits, they will be asked to:
* answer questions and surveys about their health
* have a brain MRI done
* give a small sample of blood
and at their first visit, complete a physical exam. Some participants can also do a brief test of pain sensitivity. All participants will be asked to complete a headache diary for the first 6 months, for 1 month after the 1 year visit, and for 1 month after the 2 year visit.

开始日期2024-12-31

申办/合作机构

University of Colorado Denver

100 项与睾酮相关的临床结果

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100 项与睾酮相关的转化医学

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100 项与睾酮相关的专利（医药）

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117,698

项与睾酮相关的文献（医药）

2025-12-31·Gut Microbes

Gut microbiome-driven regulation of sex hormone homeostasis: a potential neuroendocrine connection

Article

作者: Cross, Tzu-Wen L. ; Rajwa, Bartek ; Organski, Anna Clapp ; Jorgensen, Joan S. ; Reddivari, Anjali

The gut microbiome is known to have a bidirectional relationship with sex hormone homeostasis; however, its role in mediating interactions between the primary regulatory axes of sex hormones and their productions is yet to be fully understood. We utilized both conventionally raised and gnotobiotic mouse models to investigate the regulatory role of the gut microbiome on the hypothalamic-pituitary-gonadal (HPG) axis. Male and female conventionally raised mice underwent surgical modifications as follows: (1) hormonally intact controls; (2) gonadectomized males and females; (3) gonadectomized males and females supplemented with testosterone and estrogen, respectively. Fecal samples from these mice were used to colonize sex-matched, intact, germ-free recipient mice through fecal microbiota transplant (FMT). Serum gonadotropins, gonadal sex hormones, cecal microbiota, and the serum global metabolome were assessed. FMT recipients of gonadectomized-associated microbiota showed lower circulating gonadotropin levels than recipients of intact-associated microbiota, opposite to that of FMT donors. FMT recipients of gonadectomized-associated microbiota also had greater testicular weights compared to recipients of intact-associated microbiota. The gut microbiota composition of recipient mice differed significantly based on the FMT received, with the male microbiota having a more concerted impact in response to changes in the HPG axis. Network analyses showed that multiple metabolically unrelated pathways may be involved in driving differences in serum metabolites due to sex and microbiome received in the recipient mice. In sum, our findings indicate that the gut microbiome responds to the HPG axis and subsequently modulates its feedback mechanisms. A deeper understanding of interactions between the gut microbiota and the neuroendocrine-gonadal system may contribute to the development of therapies for sexually dimorphic diseases.

2025-12-31·JOURNAL OF DERMATOLOGICAL TREATMENT

Letter to the editor submitted in response to “Minoxidil: a comprehensive review”

Article

作者: Penteris, Michail ; Kontogiorgis, Christos ; Constantinides, Theodoros K. ; Kalogirou, Anastasia

A review.In this study the use of 3% minoxidil twice daily for 16 wk was superior to the placebo in increasing hair d. with no major adverse effects as assessed by the global photog. scores, change in hair d. and patients' self-assessment from baseline to the follow-up.In another case report by Pang et al. application of topical minoxidil twice daily for 5 days/wk for 3 mo was deemed effective for enhancing facial hair in a 17-yr-old transgender male not on testosterone therapy as assessed by changes in photos between the baseline and follow-up with some side effects such as skin irritation and hirsutism .We report these findings to enrich the literature and highlight the need for further randomized controlled trials (RCTs) to prove the efficacy and safety profile of topical minoxidil for enhancing growth in facial hair and addnl. evidence-based data to ensure its optimum use.

2025-12-31·Italian Journal of Animal Science

A comparative study to estimate three commercial products of human chorionic gonadotropin (hCG) on blood biochemistry, sexual hormones concentrations, reproductive indices, and larvae production of African catfish Clarias gariepinus brood-stock

作者: Ahmed, Mohammad Z. ; Abdel-Aziz, Mohamed F. A. ; Saleh, Hamed H. E. ; Attia, El-Sayed I. ; Arai, Takaomi ; Hassan, Habib Ul

Hormonal induction is an effective method for spawning African catfish, especially the use of human chorionic gonadotropin (hCG)Hormonal treatment is an essential factor in the cost of seed productionThere are many types of hCG products used in Egypt but Choriomon is the best in efficiency of reproduction and economic

224

项与睾酮相关的新闻（医药）

2025-07-14

·Business Wire

Aviva Biopharm Inc. Unveils Groundbreaking Pre-Clinical Data on d3-T, a First-in-Class Testosterone Therapy for Women at ENDO 2025

CONCORD, Mass.--(BUSINESS WIRE)--Aviva Biopharm Inc. (Aviva Bio), a clinical-stage biopharmaceutical company developing next-generation hormone therapies for women, announced today that new preclinical data on its lead compound, d3-testosterone (d3-T), was presented at ENDO 2025, the Endocrine Society’s flagship annual meeting, on July 14th in San Francisco. Aviva Bio unveils preclinical data at #ENDO2025: d3-testosterone delivers full androgen activity and strong aromatase resistance. d3-T is designed to be a safer, first-in-class testosterone therapy for women. #WomensHealth #Biotech #VC The poster, titled “Characterization of d3-Testosterone, A Novel, Non-Aromatizing Androgen,” will be presented by Judith Boice, PhD, CEO of Aviva Bio and co-author of the research. “d3-T shares all the characteristics of testosterone, but is re-engineered for safety,” said Judith Boice, PhD, CEO of Aviva Bio. “d3-T is a novel, structurally identical form of testosterone where select hydrogen molecules have been substituted with deuterium. This small change creates a significant breakthrough.” Unlike conventional testosterone, d3-T resists aromatization, the metabolic process that converts androgens into estradiol. This resistance may significantly reduce the risk of estradiol-driven side effects such as breast cancer and gynecomastia, making d3-T a potentially transformative therapy for patients. “This is a pivotal moment addressing a significant unmet need in women’s health,” said Barbara S. Levy, MD, FACOG, FACS, Chief Medical Officer, Visana Health Inc. and Clinical Professor, Obstetrics and Gynecology, The George Washington University School of Medicine and Health Sciences. “d3-T could significantly enhance options for hormone therapy in menopausal and perimenopausal women.” Key findings from the preclinical study include: d3-T is highly resistant to aromatization, as demonstrated by multiple studies in the presence of pure, concentrated aromatase d3-T is equally potent and efficacious to testosterone in inducing androgen receptor activation d3-T has similar metabolic stability and metabolite production compared with testosterone in both human and rat liver cells These data support advancing d3-T into clinical trials d3-T may be a useful alternative in clinical situations where the aromatization of testosterone limits its therapeutic potential. This safety challenge has hampered prior efforts to gain FDA approval of a testosterone product for women. d3-T addresses this challenge and holds promise for broader indications including low libido and muscle loss associated with aging and GLP-1 agonist use. Aviva Bio holds exclusive rights to d3-T and is preparing to initiate a Phase I clinical trial in early 2026. About Aviva Bio Aviva Bio is a clinical-stage biotechnology company unlocking the full potential of hormone-based medicine. Through novel drug design and a focus on unmet needs in women’s health, Aviva Bio is developing first-in-class therapeutics to improve lives. It’s lead program, AVA-291 (d3-Testosterone), is on track to become the first FDA-approved testosterone therapy designed for women. About AVA-291 (d3-Testosterone) AVA-291 or d3-testosterone (d3-T) is a structurally identical, deuterium-substituted isotopologue of testosterone designed to resist aromatization to estradiol. Conversion of testosterone into estradiol is linked with potential safety (breast cancer) and tolerability (gynecomastia) concerns associated with testosterone therapy. In vitro studies of d3-T have demonstrated a similar metabolic profile and similar androgen receptor affinity as testosterone, but unlike testosterone it is highly resistant to aromatization to estradiol. d3-T may be a useful alternative to testosterone in clinical situations where the aromatization of testosterone limits its therapeutic potential, such as hormone replacement therapy in postmenopausal women, addressing muscle wasting in patients on GLP-1 therapy, the treatment of ER+ breast cancer, or in men on testosterone therapy who develop gynecomastia.

2025-07-09

·药学进展

独家原创 | 焦宇副教授：去势抵抗性前列腺癌患者对雄激素受体拮抗剂耐药机制的研究进展

“点击蓝字关注我们焦宇中国药科大学副教授，2011 年毕业于中国科学院上海药物所，获药物化学博士学位。2016 年 9 月至 2017 年 10 月作为访问学者在美国明尼苏达大学药学院进行科研工作。现主要研究方向为：1）靶向雄激素受体的药物化学研究；2）小分子神经系统药物的发现与开发。发表 SCI 论文 21 篇（J Med Chem,Euro J Med Chem, Anal Chem 等 Q1 区期刊），授权发明专利 5 项。去势抵抗性前列腺癌患者对雄激素受体拮抗剂耐药机制的研究进展 PPS 樊亚雯，彭胜宽，裴升，焦宇*（中国药科大学理学院, 江苏南京 211198）[ 摘要 ] 前列腺癌是困扰全球男性的重大癌症疾病之一，近年来发病率不断升高。雄激素受体（androgen receptor, AR）信号通路一直是前列腺癌治疗的关键通路，据此采取的包括雄激素剥夺治疗（androgen-depri-vation therapy, ADT）、AR 拮抗剂等激素治疗方法仅对早期非转移性疾病明显有效，绝大部分患者晚期进展为去势抵抗性前列腺癌（castration-resistant prostate cancer, CRPC）。近年来，针对 CRPC 患者对 AR 拮抗剂耐药机制的研究取得了显著进展。通过对 AR 信号通路异常、AR 基因突变、AR 共调节因子改变等机制在CRPC 患者对 AR 拮抗剂耐药中的作用进行综述，并对目前 PCa 治疗中针对 AR 拮抗剂的相关耐药机制进行研究，旨在为相关新型拮抗剂的研发及临床治疗方案的设计提供参考。前列腺癌是影响男性健康的恶性肿瘤之一。随着人口老龄化和生活方式的改变，前列腺癌的发病率不断升高。据报道，2023 年美国调查数据中，全球男性患病率较高的排名前 10 的肿瘤依次是前列腺癌、肺癌、结直肠癌、膀胱癌、黑色素瘤、肾癌、非霍奇金淋巴瘤、口腔和咽喉癌、白血病、胰腺癌 [1]，其中发病率最高的前列腺癌患者约占 29%。而中国前列腺癌的发病率和死亡率也在逐年增加 [2]。尽管前列腺癌前期有可用的治疗方案，但最终仍然难以治愈。由于晚期往往会发展为去势抵抗性前列腺癌（castration-resistant prostate cancer，CRPC），因此，一直在寻找和确定更好的治疗方案 [3]。自 20 世纪 40 年代初，Huggins 和 Hodges 发现雄激素可促进前列腺肿瘤生长以来，雄激素疗法一直是前列腺癌最有效和最广泛使用的治疗方法。积极监测、局部治疗和雄激素剥夺治疗（androgen depri-vation therapy，ADT）对早期非转移性疾病非常有效，但约 10% ~ 50% 的病例最终会在 3 年内对该方法产生耐药性，称为“去势抵抗性”[4]。第 1 代雄激素受体（androgen receptor，AR）拮抗剂包括氟他胺（1）、尼鲁米特（2）和比卡鲁胺（3）（见图 1），分别于 1989 年、1995 年1996 年获得美国食品药品监督管理局（Food and Drug Administration，FDA）批准。尽管患者在疾病早期阶段接受第 1 代 AR 拮抗剂治疗后，症状表现出一定程度的缓解，但最终会获得耐药性并发展为致死性 CRPC，在临床 CRPC 患者和临床前前列腺癌细胞模型中，经常观察到 AR 过表达等耐药突变 [5]。第 2 代 AR 拮抗剂具有更高的 AR 结合亲和力和特异性，以靶向 CRPC 患者中的异常 AR 信号传导通路，如恩杂鲁胺（MDV3100，4）[6]、阿帕鲁胺（ARN-509，5）[7]、达罗鲁胺（ODM-201，6）[8]，其结构如图 2 所示。但第 2 代药物的临床治疗过程仍然不可避免地出现获得性耐药 [9]，限制了治疗方案的稳定性，因此前列腺癌的耐药性 AR 拮抗剂有待进一步研发。一项对转移性去势抵抗性前列腺癌（metastatic castration-resistant prostate cancer，mCRPC）患者的转录组测序结果表明，71.3% 的病例存在 AR 通路相关基因突变 [10]。此外，磷脂酰肌醇 3- 激酶（phosphoinositide 3-kinase，PI3K）/ 蛋白激酶 B（protein kinase B，PKB）/ 第 10 号染色体缺失的磷酸酶及张力蛋白同源物 (phosphatase and tensin homolog，PTEN)信号通路、核因子κB亚基2（nuclear factor kappa B subunit 2，NF-κB2）信号通路、无翅型 / 整合型蛋白（wingless/integrated，Wnt）信号通路等其他信号通路也与 CRPC 的耐药特性有关 [11] 。本文旨在对前列腺癌治疗中 AR 通路的耐药机制研究进行综述，为相关新型拮抗剂的设计及临床治疗方案提供参考。1雄激素受体的结构和信号通路AR 基因位于 X 染色体的长臂上，包含 8 个外显子，内含子长度不等（0.7~2.6 kb），最终编码出的蛋白质含 919 个氨基酸。AR 包含 3 个主要功能域：N 末端结构域（N-terminal domain，NTD），DNA 结合结构域（DNA binding domain，DBD）和配体结合结构域（ligand binding domain，LBD）[12]。NTD 位于 AR 的 N 端，占 AR 一半以上，保守性低，与 AR 的反式激活功能相关 [13]。NTD 包含激活功能 1（activation function 1，AF1）区，该处含两个转录激活单位：Tau-1（氨基酸 100 ~ 370）和 Tau-5（氨基酸 360 ~ 485），介导 NTD 和 LBD 之间直接的配体依赖性结构域间相互作用 [14]，有助于稳定AR 二聚体复合物并减缓配体解离速率 [15]。DBD 富含半胱氨酸，具有保守的氨基酸序列，其包含由两个锌指结构组成的核心，每个锌指结构由 4 个半胱氨酸残基组成 [16]。其中，N 端锌指结构的 α 螺旋与DNA 螺旋大沟中作为反应元件的核苷酸相互作用。另一锌指结构不与 DNA 相互作用，但其中保守氨基酸可以介导 AR 受体单体之间的二聚化，并稳定DNA 和 AR 结合的复合物。DBD 和 LBD 之间的区域为铰链区，序列保守性较差，其与 DBD 的连接处序列具有核定位功能 [17-18]。LBD 晶体结构中有由 3 个 α 螺旋形成的配体结合口袋（ligand-binding pocket，LBP），该区域需要配体结合才能激活。当 LBD 被剪接形成剪接异构体时，该蛋白可能会发生功能突变，不再需要配体结合来激活，导致蛋白表达失调。AR 属于核受体超家族中的类固醇受体 [19]，是一种配体依赖的转录因子，控制特定基因表达。生理条件下，睾酮经分泌后以游离形式进入细胞内，被转化为 5α- 二氢睾酮（dihydrotestosterone，DHT），以高亲和力与 AR 结合，引起 AR 的构象变化，使 AR 与热休克蛋白（heat shock protein，HSP）分离，随后募集共调节因子，进行二聚化后移位至细胞核中。在细胞核中，AR 二聚体与目标基因启动子区域的雄激素反应元件（androgen response element，ARE）结合，如前列腺特异性抗原（prostate specific antigen，PSA）和跨膜蛋白酶等，随后招募各种共调节蛋白以促进下游基因的转录 [19]。在雄激素非依赖性 AR 途径中，AR 和 AR 突变体可在没有雄激素启动的情况下二聚化 [20]。该情况下，AR 可以在没有雄激素情况下被表皮生长因子、胰岛素样生长因子等激活 [21]，从而导致核移位和基因转录增加。AR 不仅与正常前列腺的发育和功能相关，而且对前列腺癌细胞的生长和维持也起重要作用，在正常前列腺中，AR 的主要作用是促进上皮细胞的分化，并调节编码前列腺功能所必需的蛋白质（如前列腺特异性抗原）的基因转录；在前列腺癌患者中，雄激素代谢产物与雄激素受体结合，调节细胞周期且促进前列腺癌相关基因表达，导致前列腺癌患者的肿瘤生存、生长 [22]。2雄激素受体通路耐药机制与治疗策略AR 通路相关基因突变是产生 CRPC 耐药的主要原因 [13]。尽管临床治疗引起雄激素的合成减少，但各种 AR 基因组的突变导致 AR 信号通路激活的可能性增加，包括AR扩增、点突变和剪接突变体等，这些耐药突变使得针对前列腺癌的 AR 靶向治疗遇到困难。2.1 雄激素受体扩增在早期复发性前列腺癌患者中，经常出现 AR扩增导致的获得性耐药，致使前列腺癌细胞在低雄激素水平下持续增殖 [23]。AR 扩增是在 CRPC 组织样本中观察到的最常见遗传改变，发生在高达 50%的前列腺癌患者体内 [24]。研究表明，在产生恩杂鲁胺或者阿比特龙耐药性过程中，AR 基因扩增或过表达起着重要的作用。对恩杂鲁胺治疗后患者血浆样本中细胞游离 DNA（cell-free DNA，cf-DNA）的分析显示，AR 拷贝数增加的频率高于接受阿比特龙治疗的患者样本。与未出现 AR 扩增的患者相比，AR 扩增患者早期疾病进展的风险增加 [25]。由于 AR拮抗剂抑制前列腺上皮细胞中的 AR 转录，作为一种负反馈调节机制，AR 扩增可能是一种代偿性的耐药机制。当药物 AR 拮抗作用较强，癌细胞则通过代偿性地增加 AR 表达来减弱治疗效果。全基因组测序结果表明，AR 扩增不仅是 AR 基因的扩增，而且通常包含其远端相关增强子的扩增 [26]。该增强子位于 AR 基因上游约 650 kb 的位置，常在 CRPC患者体内激活。已上市恩杂鲁胺为代表的具有更高AR 拮抗活性的第 2 代 AR 拮抗剂很好地改善了这一临床问题 [9]。2.2 雄激素受体点突变早期前列腺癌患者中，AR 基因突变较为罕见，但晚期雄激素非依赖性前列腺癌患者体内，AR 点突变频率显著增加。20% 的晚期 CRPC 患者体内发现 AR 突变，最常见的是 AR 的 LBD 区 [27]，包括氨基酸残基 F877L、H875Y、T878A、L702H 等，这些突变几乎都是由于体细胞突变造成的单碱基替换而 LBD 区常作为第 1 代和第 2 代 AR 拮抗剂的作用靶点。AR 点突变常分为两类，一种是将 AR 拮抗剂转化为激动剂（例如 F877L，W742L/C）的突变；另一种是导致配体特异性扩大，使 AR 可以与其他内源性类固醇结合的突变。T878A 是 CRPC 中最常见的点突变之一。1994年，Gaddipati 等 [28] 对 mCRPC 患者的前列腺组织标本进行分析，发现部分患者存在 T878A 突变。体外实验表明，存在 T878A 的癌细胞表现出雄激素非依赖性 AR 转录激活性质，增加了 AR 对雌激素、孕激素等的亲和力 [29]。2021 年研究发现，T878A 突变还可使 AR 被糖皮质激素（如地塞米松）等激活，导致患者产生耐药性 [30]。突变后 AR 配体结合口袋处丙氨酸残基取代苏氨酸残基，丙氨酸是一种体积小于苏氨酸的氨基酸，因此，显著增加配体结合口袋的大小，使许多其他配体如雌二醇能够与 AR 结合，从而激活 AR 信号通路 [29]。2003 年的一项研究表明，将 LNCaP 细胞在体外暴露于比卡鲁胺6~13周内，最初生长会受到抑制，但后期将会通过 W742C 或 W742L 突变，使比卡鲁胺变为 AR 激动剂 [31]。2022 年研究发现，W742C突变可能通过影响 AR 的特定功能区，而非单纯扩大结合口袋，导致癌细胞发生耐药 [32]。W742L 突变可使比卡鲁胺转变为 AR 激动剂，但第 2 代抗雄药物（如恩杂鲁胺）仍能有效抑制该突变。长期使用恩杂鲁胺治疗的前列腺癌患者的癌细胞中可能发生 F877L 突变。这种突变可能改变恩杂鲁胺与 AR 结合的方式，从而使其对 AR 的作用由拮抗转变为激动。一项体外实验研究中，恩杂鲁胺在癌细胞同时具有 T878A 和 F877L 突变的情况下比单独存在 F877L 突变时表现出更强的激动效应 [33]。相反，达罗鲁胺在体外对 F877L 突变以及含其他AR 点突变的情况下显示出较强拮抗活性 [34]。此外，F877L 突变仍保留对比卡鲁胺的敏感性，因此不同结构 AR 拮抗剂的联合用药为临床治疗恩杂鲁胺耐药的前列腺癌患者提供了一种新的治疗策略。此外，H875Y 突变可使雌激素和黄体酮能够激活 AR 通路 [35]。L702H 突变可使糖皮质激素与 AR结合，常与阿比特龙耐药、强的松激活 AR 有关 [36]。2.3 雄激素受体剪接突变体AR 的选择性剪接是另一种与 CRPC 进展有关的耐药机制，18 个 AR 剪接变异体的转录结构已经完全确定，AR-V7 作为唯一已知编码的临床样本中可检测到的 AR 选择性剪接突变体，已被证实其与苯扎鲁胺和阿比特龙的耐药性存在临床关联 [37]。该剪接突变体编码 1 个截断的 AR 蛋白，此蛋白缺乏 C-末端 LBD 区，保留反式激活 NTD 区，这种构象变化使得该蛋白无法有效结合配体，但其作为转录因子具有转录活性，能够促进靶基因的激活。此外，有研究表明，AR-V7 具有不同于野生型 AR 核位移途径和较高的核位移效率。研究表明，AR-V7 对紫杉醇（7）等紫杉烷类广谱抗癌药暂时没有明显耐药性，因此可以考虑联合用药。此外，HSP 家族也与 AR 信号通路相关。HSP 27 是一种保证 AR 稳定性的细胞保护性伴侣蛋白，一项通过利用化学合成的 α-甲基酰基辅酶 A 消旋酶小干扰 RNA（alpha-methylacyl-CoA racemase small interfering RNA，AMACR siRNA）和多西他赛（8）进行的体外研究表明多西他赛和AMARC 抑制剂的双重治疗可能通过下调 HSP 27 来降低 AR-V7 的表达 [38]。HSP 90 是一种依赖三磷酸腺苷（adenosine triphosphate，ATP）的分子伴侣，与 HSP 70 及共伴侣形成动态伴侣复合物，调节包括 AR 在内的 200 多种蛋白的折叠和稳定性。一项研究发现天然抗疟药物布鲁生坦（9）可通过破坏HSP 90 与全长 AR 或 AR-V7 的相互作用，从而达到阻断 AR 信号通路的效果 [39]。甜橙黄酮（10）是一种多甲氧基类黄酮，可在体外诱导 AR-V7 的蛋白酶体降解，增强 AR-V7 阳性细胞对恩杂鲁胺的敏感性。2.4 共调节因子AR 对下游基因的转录激活功能由 150 多个共同调节因子控制，这些因子具有多种作用，包括RNA 剪接、转录因子的招募或通过磷酸化、甲基化或泛素化来调节转录复合体中的其他蛋白质。可分为共激活因子（co-activator）和共抑制因子（co-repressor）。共激活因子 FKBP51 是一种 HSP 90 辅伴侣，已被证明在具有去势抗药性小鼠中会过表达，从而促使 AR 相关超级伴侣复合体的形成，刺激 AR 与雄激素结合。有研究表明，AR-V7 高表达的患者体内检测到 FKBP51 水平升高，通过使用特定的抑制剂来结合 FKBP51 或 FKBP52（另一种 AR 共激活因子），可减少 AR 二聚体的形成 [40]。类固醇受体辅活化子（steroid receptor coactivator，SRC）以激素依赖的方式增强 AR 诱导转录信号。SCR 家族包含 3 个与前列腺癌进展相关的成员，SRC1，SRC2 和 SRC3，其中，SRC1 的磷酸化会导致AR 信号通路的激活 [41]。通过破坏 SRC1/2 和 AR 之间的相互作用，可以抑制 CRPC 癌细胞的 AR 活性 [42]。此外，Galectin-3 已被证明可以增强 AR 转录活性，导致某些 AR 下游基因的过表达，如 KLK3 和TMPRSS2。这表明 Galectin-3 在 CRPC 中可作为潜在靶点 [43]。2.5 转录后调控AR 的转录后调控是指通过乙酰化、磷酸化、甲基化、小泛素样修饰蛋白（small ubiquitin-like modifier，SUMO）化等维持细胞的生长和存活。雄激素受体降解蛋白 1（androgen receptor degradation protein 1，ARD1）是一种乙酰基转移酶，与 AR 和HSP 90 形成复合体，导致 AR 乙酰化、核移位和靶基因表达从而导致前列腺癌发生。体外和体内模型已经证明敲除 ARD1 基因可抑制 AR 的核移位 [44]，表明该基因可作为 AR 耐药治疗的新靶点。AR 丝氨酸 81（S81）处的磷酸化与 AR 重新激活有关，该磷酸化由细胞周期依赖性激酶 1（cyclin-dependent kinase 1，CDK1）和 CDK9 调控，暗示了 CDK 抑制剂在治疗CRPC 过程中的潜在作用。SUMO 化是指一种类似泛素的蛋白与靶蛋白共价结合的过程，通常可抑制 AR转录活性。SUMO 化和去 SUMO 之间的不平衡可导致肿瘤进展。此外，临床研究显示，AR 相关基因高甲基化的患者在 ADT 治疗后的预后情况更差。3结语与展望AR 信号通路在前列腺癌的各个阶段都有着重要作用，最近的研究结果表明，在高达 70% 的肿瘤表现出不同 AR 突变的患者中，AR 信号持续起着关键作用。目前已知的 AR 拮抗剂主要作用于其 LBD区，且该区域常作为耐药突变位点，导致前列腺癌患者的获得性耐药。当患者达到去势抵抗阶段，新出现的第 2 代抗雄激素药物如醋酸阿比特龙、阿帕鲁胺、恩杂鲁胺或达罗鲁胺虽能一定程度上抑制病情进展，但对包括 AR 的选择性剪接突变体、基因点突变等在内的复合型 AR 耐药突变仍然没有有效的治疗效果，使得目前 AR 拮抗剂治疗前列腺癌遭遇瓶颈。因此，目前临床上基于解决 CRPC 的关键问题是灵活选择不同治疗方案或多种治疗策略联合使用，以及新的克服 AR 耐药突变的药物发现。本研究简述了与 AR 信号通路相关的耐药突变机制研究，为新型 AR 拮抗剂的研发及创新性临床治疗方案的选择提供参考，以克服前列腺癌涉及的原发性或获得性耐药机制，有助于提升医师的临床决策强度。参考文献： [1] Siegel R L, Miller K D, Wagle N S, et al. 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JAMA Oncol, 2016, 2(12): 1598-1606.[26] Xiang R R, Lee S A, Tyndall C F, et al. CRISPR screening identifies regulators of enhancer-mediated androgen receptor transcription in advanced prostate cancer[J/OL]. Cell Rep, 2025, 44(2): 115312[2025-05-10]. https://doi.org/10.1016/j.celrep.2025.115312.[27] Chung C, Abboud K. Targeting the androgen receptor signaling pathway in advanced prostate cancer[J]. Am J Health Syst Pharm,2022, 79(15): 1224-1235.[28] Gaddipati J P, McLeod D G, Heidenberg H B, et al. Frequent detection of codon 877 mutation in the androgen receptor gene in advanced prostate cancers[J]. Cancer Res, 1994, 54(11): 2861-2864.[29] Sun C, Shi Y, Xu L L, et al. Androgen receptor mutation (T877A) promotes prostate cancer cell growth and cell survival[J]. Oncogene, 2006, 25(28): 3905-3913.[30] Liu H L, An X L, Li S Y, et al. Interaction mechanism exploration of R-bicalutamide/S-1 with WT/W741L AR using molecular dynamics simulations[J]. Mol Biosyst, 2015, 11(12): 3347-3354.[31] Hara T, Miyazaki J, Araki H, et al. Novel mutations of androgen receptor: a possible mechanism of bicalutamide withdrawal syndrome[J]. Cancer Res, 2003, 63(1): 149-153.[32] Shiota M, Akamatsu S, Tsukahara S,et al. Androgen receptor mutations for precision medicine in prostate cancer[J]. Endocr Relat Cancer, 2022, 29(10): R143-R155.[33] Prekovic S, van Royen M E, Voet A R D, et al. The effect of F877L and T878A mutations on androgen receptor response to enzalutamide[J]. Mol Cancer Ther, 2016, 15(7): 1702-1712.[34] Sugawara T, Baumgart S J, Nevedomskaya E, et al. Darolutamide is a potent androgen receptor antagonist with strong efficacy in prostate cancer models[J]. Int J Cancer, 2019, 145(5): 1382-1394.[35] Vasudevamurthy A K, Ledet E, Garvey C, et al. Estrogen-mediated activation of H875Y androgen receptor mutation in a prostate cancer patient[J]. Clin Genitourin Cancer, 2017, 15(1): e111-e113.[36] Crona D J, Whang Y E. Androgen receptor-dependent and -independent mechanisms involved in prostate cancer therapy resistance[J/OL]. Cancers (Basel), 2017, 9(6): 67[2024-05-10]. https://pmc.ncbi.nlm.nih.gov/articles/PMC5483886/. DOI: 10.3390/cancers9060067.[37] Zheng Z Y, Li J X, Liu Y K, et al. The crucial role of AR-V7 in enzalutamide-resistance of castration-resistant prostate cancer[J/OL]. Cancers (Basel), 2022, 14(19): 4877[2024-05-10]. https://doi.org/10.3390/cancers14194877.[38] Yoshizawa A, Takahara K, Saruta M, et al. Combined alpha methylacyl-CoA racemase inhibition and docetaxel treatment reduce cell proliferation and decrease expression of heat shock protein 27 in androgen receptor-variant-7-positive prostate cancer cells[J]. Prostate Int, 2021, 9(1): 18-24.[39] Moon S J, Jeong B C, Kim H J, et al. Bruceantin targets HSP90 to overcome resistance to hormone therapy in castration-resistant prostate cancer[J]. Theranostics, 2021, 11(2): 958-973.[40] Maeda K, Habara M, Kawaguchi M, et al. FKBP51 and FKBP52 regulate androgen receptor dimerization and proliferation in prostate cancer cells[J]. Mol Oncol, 2022, 16(4): 940-956.[41] Xu J M, Wu R C, O'Malley B W. Normal and cancer-related functions of the p160 steroid receptor co-activator (SRC) family[J]. Nat Rev Cancer, 2009, 9(9): 615-630.[42] Fancher A T, Hua Y, Close D A, et al. Characterization of allosteric modulators that disrupt androgen receptor co-activator protein-protein interactions to alter transactivation-drug leads for metastatic castration resistant prostate cancer[J]. SLAS Discov, 2023, 28(7): 325-343.[43] Dondoo T O, Fukumori T, Daizumoto K, et al. Galectin-3 is implicated in tumor progression and resistance to anti-androgen drug through regulation of androgen receptor signaling in prostate cancer[J]. Anticancer Res, 2017, 37(1): 125-134.[44] Kuhns K J, Zhang G Y, Wang Z H, et al. ARD1/NAA10 acetylation in prostate cancer[J]. Exp Mol Med, 2018, 50(7): 1-8.美编排版：史鑫宇感谢您阅读《药学进展》微信平台原创好文，也欢迎各位读者转载、引用。本文选自《药学进展》2025年第 5 期。《药学进展》杂志由教育部主管、中国药科大学主办，中国科技核心期刊（中国科技论文统计源期刊）。刊物以反映药学科研领域的新方法、新成果、新进展、新趋势为宗旨，以综述、评述、行业发展报告为特色，以药学学科进展、技术进展、新药研发各环节技术信息为重点，是一本专注于医药科技前沿与产业动态的专业媒体。《药学进展》注重内容策划、加强组稿约稿、深度挖掘、分析药学信息资源、在药学学科进展、科研思路方法、靶点机制探讨、新药研发报告、临床用药分析、国际医药前沿等方面初具特色；特别是医药信息内容以科学前沿与国家战略需求相合，更加突出前瞻性、权威性、时效性、新颖性、系统性、实战性。根据最新统计数据，刊物篇均下载率连续三年蝉联我国医药期刊榜首，复合影响因子1.216，具有较高的影响力。《药学进展》编委会由国家重大专项化学药总师陈凯先院士担任主编，编委由新药研发技术链政府监管部门、高校科研院所、制药企业、临床医院、CRO、金融资本及知识产权相关机构近两百位极具影响力的专家组成。联系《药学进展》↓↓↓编辑部官网：pps.cpu.edu.cn；邮箱：yxjz@163.com；电话：025-83271227。欢迎投稿、订阅！往期推荐聚焦“兴药为民·2023生物医药创新融合发展大会”“兴药为民·2023生物医药创新融合发展大会”盛大启幕！院士专家齐聚杭城，绘就生物医药前沿赛道新蓝图“兴药强刊”青年学者论坛暨《药学进展》第二届青年编委会议成功召开“兴药为民·2023生物医药创新融合发展大会”路演专场圆满收官！校企合作新旅程已启航我知道你在看哟

放射疗法

2025-06-09

·PRNewswire

Lipocine Announces Filing of New Drug Submission for TLANDO® in Canada

New Drug Submission filed by Lipocine's licensing partner Verity Pharma Over 700,000 total prescriptions written annually for testosterone replacement therapy (TRT) in Canada, representing large commercial opportunity SALT LAKE CITY, June 9, 2025 /PRNewswire/ -- Lipocine Inc. (NASDAQ: LPCN), a biopharmaceutical company leveraging its proprietary technology platform to enable effective oral delivery of therapeutics, today announced that its licensing partner, Verity Pharma, filed a New Drug Submission (NDS) for TLANDO® in Canada. TLANDO is the first and only oral testosterone replacement therapy (TRT) option approved by the US Food and Drug Administration (FDA) that does not require dose titration. "Canada represents an attractive market for TLANDO and the filing of the NDS by Verity Pharma represents an important next step in making the product available there," said Mahesh Patel, CEO of Lipocine. "We believe that, if approved, the introduction of this new and highly differentiated oral TRT option has the potential to drive significant market gains." There are over 700,000 prescriptions written annually in Canada for TRT, and approximately 50% of this patient population is covered through private insurance. In addition, there are limited promotional activities surrounding currently available TRTs, which could provide an opportunity for TLANDO to capture a significant share of this large and growing market. In January 2024, Lipocine and Verity Pharma entered into an exclusive license agreement under which Verity Pharma gained the commercial rights to TLANDO® in the United States and Canada. About TLANDO TLANDO is approved by the US FDA as a testosterone replacement therapy (TRT) in adult males indicated for conditions associated with a deficiency or absence of endogenous testosterone: primary hypogonadism (congenital or acquired) and hypogonadotropic hypogonadism (congenital or acquired). It was developed using Lipocine's proprietary Lip'ral drug delivery technology platform. For full prescribing information, please visit . About Lipocine Lipocine is a biopharmaceutical company leveraging its proprietary technology platform to enable effective oral delivery of therapeutics. Lipocine has drug candidates in development as well as drug candidates for which we are exploring partnerships. Our drug candidates represent enablement of differentiated, patient friendly oral delivery options for favorable benefit to risk profile which target large addressable markets with significant unmet medical needs. Lipocine's clinical development candidates include: LPCN 1154, oral brexanolone, for the potential treatment of postpartum depression, LPCN 2101 for the potential treatment of epilepsy, LPCN 2203 an oral candidate targeted for the management of essential tremor, LPCN 2401 an oral proprietary anabolic androgen receptor agonist, as an adjunct therapy to incretin mimetics, as an aid for improved body composition in obesity management and LPCN 1148, a novel androgen receptor agonist prodrug for oral administration targeted for the management of symptoms associated with liver cirrhosis. Lipocine is exploring partnering opportunities for LPCN 1107, our candidate for prevention of preterm birth, LPCN 1154, for rapid relief of postpartum depression, LPCN 2401 for obesity management, LPCN 1148, for the management of decompensated cirrhosis, and LPCN 1144, our candidate for treatment of metabolic dysfunction-associated steatohepatitis (MASH). TLANDO, a novel oral prodrug of testosterone containing testosterone undecanoate developed by Lipocine, is approved by the FDA for conditions associated with a deficiency of endogenous testosterone, also known as hypogonadism, in adult males. For more information, please visit . Forward-Looking Statements This release contains "forward-looking statements" that are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995 and include statements that are not historical facts regarding our product candidates and related clinical trials, our development of our product candidates and related efforts with the FDA, including with respect to LPCN 1154, our P3 safety and efficacy study relating to LPCN 1154, the timing and potential results of the safety and efficacy study relating to LPCN 1154, potential partnering of our product candidates with third parties, and the potential uses and benefits of our product candidates. Investors are cautioned that all such forward-looking statements involve risks and uncertainties, including, without limitation, the risks that we may not be successful in developing product candidates, we may not have sufficient capital to complete the development processes for our product candidates or we may decide to allocate our available capital to other product candidates, we may not be able to enter into partnerships or other strategic relationships to monetize our non-core assets, safety and efficacy studies, including those relating to LPCN 1154, may not be successful or may not provide results that would support the submission of a NDA, the FDA may not approve any of our products, risks related to our products, expected product benefits not being realized, clinical and regulatory expectations and plans not being realized, new regulatory developments and requirements, risks related to the FDA approval process including the receipt of regulatory approvals and our ability to utilize a streamlined approval pathway for LPCN 1154, the results and timing of clinical trials, patient acceptance of Lipocine's products, the manufacturing and commercialization of Lipocine's products, and other risks detailed in Lipocine's filings with the SEC, including, without limitation, its Form 10-K and other reports on Forms 8-K and 10-Q, all of which can be obtained on the SEC website at . Lipocine assumes no obligation to update or revise publicly any forward-looking statements contained in this release, except as required by law. SOURCE Lipocine Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

引进/卖出上市批准

100 项与睾酮相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D00075	睾酮	G03BA03	DB00624

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
继发性睾丸衰竭	美国	Endo Operations Ltd.	2010-12-29
心理性性功能障碍	欧盟	Warner Chilcott Ltd.	2006-07-28
心理性性功能障碍	欧盟	Teva NI Ltd.	2006-07-28
心理性性功能障碍	冰岛	Teva NI Ltd.	2006-07-28
心理性性功能障碍	冰岛	Warner Chilcott Ltd.	2006-07-28
心理性性功能障碍	列支敦士登	Warner Chilcott Ltd.	2006-07-28
心理性性功能障碍	列支敦士登	Teva NI Ltd.	2006-07-28
心理性性功能障碍	挪威	Teva NI Ltd.	2006-07-28
心理性性功能障碍	挪威	Warner Chilcott Ltd.	2006-07-28
低睾酮水平	美国	Endo Operations Ltd.	2002-10-31
睾酮缺乏	澳大利亚	Teva Pharmaceuticals Australia Pty Ltd	2002-04-10
性腺机能减退	美国	AbbVie, Inc.	1995-09-29

未上市

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
先天性睾丸发育不全综合征	临床3期	美国	Amneal Pharmaceuticals, Inc.	2014-03-01
关节痛	临床3期	美国	Alliance Foundation Trials LLC	2013-09-10
关节痛	临床3期	波多黎各	Alliance Foundation Trials LLC	2013-09-10
乳腺癌	临床3期	美国	Alliance Foundation Trials LLC	2013-09-10
乳腺癌	临床3期	波多黎各	Alliance Foundation Trials LLC	2013-09-10
潮热	临床3期	美国	Alliance Foundation Trials LLC	2013-09-10
潮热	临床3期	波多黎各	Alliance Foundation Trials LLC	2013-09-10
肌肉骨骼畸形	临床3期	美国	Alliance Foundation Trials LLC	2013-09-10
肌肉骨骼畸形	临床3期	波多黎各	Alliance Foundation Trials LLC	2013-09-10
阿尔茨海默症	临床3期	美国	Solvay Pharmaceuticals, Inc.	2009-07-01

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT06154200 (CTgov)	临床2期	干燥综合征 \| 干眼综合征 \| 睑板腺功能障碍	24	Vehicle gel (Vehicle Gel)	遞範繭鑰淵鬱衊齋廠製(蓋壓壓醖窪獵夢廠衊顧) = 鹹鹹艱齋觸齋鬱選範鏇選鬱蓋艱襯網製糧憲網 (積齋廠齋簾鬱衊鬱選積, 1.2) 更多	-	2025-05-25
				Testosterone gel 4.5% (Testosterone Gel 4.5%)	遞範繭鑰淵鬱衊齋廠製(蓋壓壓醖窪獵夢廠衊顧) = 膚範構繭鬱鹹夢積鑰繭選鬱蓋艱襯網製糧憲網 (積齋廠齋簾鬱衊鬱選積, 1.3) 更多
NCT04456296 (CTgov)	临床4期	继发性睾丸衰竭 \| 无睾症	673	AVEED (AVEED® (Testosterone Undecanoate Injection))	願蓋構膚廠衊願觸艱遞(齋鬱壓築構膚鹹糧鏇範) = 醖製遞窪製廠繭願壓鹽憲選膚憲網築選衊鑰觸 (鹹顧廠鏇憲積憲繭襯選, 鑰繭繭窪網鑰齋廠鏇鹽 ~ 廠顧築齋夢鹽築鑰蓋壓) 更多	-	2025-03-14
				FORTESTA (FORTESTA® (Testosterone Gel))	願蓋構膚廠衊願觸艱遞(齋鬱壓築構膚鹹糧鏇範) = 範選築簾構夢鬱選築夢憲選膚憲網築選衊鑰觸 (鹹顧廠鏇憲積憲繭襯選, 網獵構簾積積餘窪衊鹹 ~ 願積醖淵願築淵鑰鏇艱) 更多
NCT02432261 (CTgov)	临床1期	-	44	Nestorone® /testosterone gel (Group 1)	醖獵淵鬱範鹹鬱襯積鹹 = 觸網製膚襯憲願繭鬱顧顧憲蓋醖製鑰遞膚構膚 (構鑰膚觸衊齋選艱築襯, 鹽襯願選窪繭觸襯製範 ~ 製鹽壓顧醖鹽選憲醖餘) 更多	-	2025-02-13
				Testosterone only gel (Group 2)	醖獵淵鬱範鹹鬱襯積鹹 = 鹽網網淵餘構積遞範鏇顧憲蓋醖製鑰遞膚構膚 (構鑰膚觸衊齋選艱築襯, 艱構醖遞觸積艱淵醖構 ~ 願獵鹽鑰廠餘製鏇繭網) 更多
NCT02938923 (STEP-HI, CTgov)	临床3期	髋部骨折 \| 股骨颈骨折 \| 肌肉减少症	129	Testosterone+Supervised exercise training (Exercise + Testosterone (EX + T))	獵糧艱襯遞淵積憲衊鏇(醖鏇遞鏇網餘蓋顧膚積) = 鹹願築鑰獵夢鹹襯淵遞衊夢窪願淵壓襯繭願膚 (襯獵範製壓鹹艱鹽鏇繭, 蓋選獵築製鑰鹹獵範範 ~ 醖餘齋齋醖繭襯構鏇網) 更多	-	2025-02-04
				Supervised exercise training (Exercise + Placebo (EX + P))	獵糧艱襯遞淵積憲衊鏇(醖鏇遞鏇網餘蓋顧膚積) = 襯網繭齋餘積觸構選築衊夢窪願淵壓襯繭願膚 (襯獵範製壓鹹艱鹽鏇繭, 齋觸積鑰襯製鹹齋齋餘 ~ 衊製積網鏇獵簾簾蓋齋) 更多
UEGW2024	N/A	原发性恶性肝肿瘤 testosterone \| estradiol \| tumor necrosis factor receptor superfamily member 9 (TNFRS9) ... 更多	-	TESTOSTERONE (Estradiol levels)	膚蓋鑰構淵鹹鹽夢廠選(壓壓艱鏇鑰範製齋蓋積) = 蓋糧簾餘憲鑰觸積齋膚鏇衊糧憲鹽鹹鹹製壓餘 (蓋膚範膚遞繭獵衊夢鹹 ) 更多	积极	2024-10-13
ADA2024	N/A	肥胖	-	Testosterone Replacement Therapy (TRT)	構鑰壓遞淵範範網餘網(築製糧願遞窪窪繭鏇蓋) = 憲衊醖餘鬱艱艱蓋齋蓋顧網壓壓繭鬱鏇窪構簾 (簾鹽齋艱衊蓋願範鬱糧 ) 更多	-	2024-06-14
Testosterone Modulation of Muscle Transcriptome Profile (ENDO2024)	N/A	性腺机能减退 \| 肥胖 early AM testosterone	83	Testosterone Replacement + Lifestyle Therapy	構範選獵艱鏇壓鹹壓糧(夢窪觸網構襯顧壓鏇顧) = 艱糧選繭蓋鹽憲獵艱顧選網淵鏇窪鹽繭積醖積 (醖鬱築範窪範鬱築齋醖 ) 更多	积极	2024-06-01
				Placebo + Lifestyle Therapy	構範選獵艱鏇壓鹹壓糧(夢窪觸網構襯顧壓鏇顧) = 製膚衊襯製蓋鹹鹽簾積選網淵鏇窪鹽繭積醖積 (醖鬱築範窪範鬱築齋醖 ) 更多
Near Term Cardiometabolic Outcomes in Transgender Boys and Men (ENDO2024)	N/A	E2	51	Transgender Men on Testosterone Therapy	憲製遞糧衊壓製夢觸製(壓膚獵範膚襯餘鑰範壓) = 憲齋壓窪糧憲願壓齋觸獵淵憲壓廠糧遞網膚齋 (艱膚繭積膚獵襯齋鏇壓 ) 更多	-	2024-06-01
Testosterone II (TSTII) (ENDO2024)	N/A	肾细胞癌 testosterone	-	Testosterone II (TSTII) Immunoassay (Atellica IM Testosterone II (TSTII) assay)	夢夢壓獵積遞淵齋鹹襯(獵積艱鹽鹹夢艱淵廠顧) = 鹹鏇壓築鑰遞醖繭夢壓蓋鏇廠夢繭鹹淵齋壓網 (鹹憲範網顧憲網構膚獵 )	-	2024-06-01
				Testosterone II (TSTII) Immunoassay (ADVIA Centaur Testosterone II (TSTII) assay)	夢夢壓獵積遞淵齋鹹襯(獵積艱鹽鹹夢艱淵廠顧) = 範艱簾鹽顧襯繭蓋襯簾蓋鏇廠夢繭鹹淵齋壓網 (鹹憲範網顧憲網構膚獵 )
ATS2024	N/A	急性肺损伤	-	Anabolic Testosterone Isocaproate	醖構糧鹽範鏇鏇鹹艱蓋(醖製鏇襯顧積糧憲選膚) = Our patient is a 46-year-old smoker who presented with two days of progressively dyspnea preceded by two weeks of cough. His history was significant for polysubstance use disorder. In the emergency department, he was found to be hypoxic to 60% with diffuse crackles and expiratory wheezes on exam, so he was given a dose of systemic steroids and started nebulizers. Chest radiograph and chest CT scan (figure 1) showed diffuse bilateral ground glass opacities. His respiratory status deteriorated rapidly, and he was intubated, then he was ultimately admitted to the MICU for acute hypoxemic respiratory failure. All infectious work-up including sputum culture and rapid respiratory pathogen PCR were negative. Over the next three days, he continued to have higher oxygen requirements, so empiric steroids were given then flexible bronchoscopy was performed with BAL demonstrating eosinophils of 14%, and lymphocytes of 3%. BAL bacterial and fungal cultures were negative. He was started on IV methylprednisolone, responded very well and after 3 days he was extubated. Following extubation, he reported using non-prescribed anabolic testosterone isocaproate for bodybuilding over the past several months and had three similar presentations with respiratory distress with chest CT also showing bilateral ground glass opacities and negative infectious workup. In all of them, he exhibited clinical improvement following each of these presentations with normal chest radiographs in between. He was followed in pulmonary clinic and was advised to stop using anabolic steroids with no recurrence to date. 鑰艱簾選憲鬱繭夢壓築 (鬱範獵衊襯廠鏇簾窪廠 )	-	2024-05-19