Androgens

Androgens: Clinical Research and TherapeuticsVol. 2, No. 1 Editorial CommentOpen AccessCreative Commons licenseTestosterone Therapy in Men with Advanced Prostate Cancer: Too Many Unknowns for Safe UseJesse Ory and Ranjith RamasamyJesse OryDepartment of Urology, University of Miami, Miami Florida, USA.Search for more papers by this author and Ranjith Ramasamy*Address correspondence to: Ranjith Ramasamy, MD, Department of Urology, University of Miami, 1150 NW 14th Street, Suite 309, Miami, FL 33136, USA, E-mail Address: ramasamy@miami.eduDepartment of Urology, University of Miami, Miami Florida, USA.Search for more papers by this authorPublished Online:21 Jul 2021https://doi.org/10.1089/andro.2021.0015AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail Accepted practice surrounding the use of exogenous testosterone in the presence of treated or untreated localized prostate cancer has changed dramatically over the past decade. Recent evidence has failed to show an increased risk of de novo disease in the general population,1 or of progression or recurrence in men after definitive therapy or on active surveillance for localized disease.2 This has culminated in recent American Urological Association guidelines on testosterone therapy (TT) reinforcing the lack of evidence connecting TT to de novo prostate cancer, and supporting the safety of TT in men with treated prostate cancer—primarily in men with low or intermediate risk disease.1This is all predicated on the saturation hypothesis: that prostate cells will not respond to testosterone above a certain “saturation” threshold, thought to be between 100 and 200 ng/dL.3 In this article, TT in men with biochemical recurrence and metastatic prostate cancer: initial observations by Morgentaler et al.,4 the authors recognize the lack of evidence in men with advanced disease, the morbidity caused by androgen deprivation, and hypothesize that based on prior evidence in localized disease, that testosterone in these men may be safe.This hypothesis is predicated on the assumption that the saturation hypothesis applies to men with mutated prostate cancer cell lines, as often happens with metastasis or advanced disease.5,6 This is likely not the case, as one can see from data in this series. Prostate-specific antigen increased by >10 points in men with biochemical recurrence and metastatic disease, in men with a mean testosterone of 204 ng/dL (range 3–629), above the proposed saturation threshold. In addition, 5 of 22 men died, with 3 dying while on testosterone. Only 10 men of 22 had follow-up imaging, 3 of which showed progression. This seems in line with existing evidence in advanced prostate cancer: increasing testosterone >20 ng/dL in men with metastatic or recurrent prostate cancer is associated with worse outcomes.7 Regardless, the authors have made it clear that men were thoroughly counseled as to the potential risks of TT, and all had spoken to their oncologists beforehand.Although there is no doubt that these men likely had symptoms severely impacting their quality of life, these data stress the importance of involving the patient's oncologist and thoroughly counseling them as to the risks of pursuing testosterone in this disease state. Some men had normal serum testosterone in this study, highlighting the importance of searching for other causes of their symptoms before starting them on a medication that may hasten their death. Research into the use of human chorionic gonadotropin or selective estrogen receptor modulators in this population may be worthwhile, as the mutated androgen receptor would be exposed to less testosterone than with exogenous T. Ultimately, until more data are collected, patients must balance the prospect of symptom improvement with the real possibility of progression or death. A multidisciplinary approach should be pursued in these difficult cases, and more in vitro research should be conducted before further use in patients.Authors' ContributionsDesign and writing of article by J.O. Design, concept, and editing by R.R.Author Disclosure StatementJ.O. and R.R. have nothing to disclose.Funding InformationNo funding information to declare.References1. Mulhall J, Trost L, Brannigan R, et al. Evaluation and management of testosterone deficiency: AUA guideline. J Urol. 2018;200(2):423–432. Crossref, Medline, Google Scholar2. Ory J, Flannigan R, Lundeen C, Huang JG, Pommerville P, Goldenberg SL. Testosterone therapy in patients with treated and untreated prostate cancer: Impact on oncologic outcomes. J Urol. 2016;196(4):1082–1089. Crossref, Medline, Google Scholar3. Morgentaler A, Traish AM. Shifting the paradigm of testosterone and prostate cancer: The saturation model and the limits of androgen-dependent growth. Eur Urol. 2009;55(2):310–320. Crossref, Medline, Google Scholar4. Morgentaler A, Abello A, Bubley G. Testosterone therapy in men with biochemical recurrence and metastatic prostate cancer: Initial observations. Androgens Clin Res Therapeutics. 2021;2:121–128. Link, Google Scholar5. Heinlein CA, Chang C. Androgen receptor in prostate cancer. Endocr Rev. 2004;25(2):276–308. Crossref, Medline, Google Scholar6. Brooke GN, Bevan CL. The role of androgen receptor mutations in prostate cancer progression. Curr Genom. 2009;10(1):18–25. Crossref, Medline, Google Scholar7. Klotz L, Shayegan B, Guillemette C, et al. Testosterone suppression in the treatment of recurrent or metastatic prostate cancer—A Canadian consensus statement. Can Urol Assoc J. 2018;12(2):30–37. Crossref, Medline, Google ScholarCite this article as: Ory J, Ramasamy R (2021) Testosterone therapy in men with advanced prostate cancer: too many unknowns for safe use, Androgens: Clinical Research and Therapeutics 2.1, 131–132, DOI: 10.1089/andro.2021.0015.Abbreviation UsedTTtestosterone therapyFiguresReferencesRelatedDetails Volume 2Issue 1Dec 2021 Information© Jesse Ory and Ranjith Ramasamy 2021; Published by Mary Ann Liebert, Inc.To cite this article:Jesse Ory and Ranjith Ramasamy.Androgens: Clinical Research and Therapeutics.Dec 2021.131-132.http://doi.org/10.1089/andro.2021.0015Published in Volume: 2 Issue 1: July 21, 2021Open accessThis Open Access article is distributed under the terms of the Creative Commons License [CC-BY] ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.PDF download

Jesse Ory

Ranjith Ramasamy

Androgens Clinical Research and Therapeutics

Testosterone Therapy in Men with Advanced Prostate Cancer: Too Many Unknowns for Safe Use

晚期前列腺癌男性患者中的睾酮治疗：未知因素过多，安全性存疑

Introduction: Lipedema is an abnormal deposit of subcutaneous fat most often involving the lower limbs symmetrically. The physiopathology is poorly understood, but its peak of the almost exclusively female involvement and its peak of appearance at puberty, during pregnancy or at menopause orient toward a hormonal involvement, whereas other elements are in favor of a strong genetic predisposition. Klinefelter syndrome (KS) is a genetic disease linked to aneuploidy resulting in a karyotype 47 XXY most of the time. There is a substantial variation in clinical presentation, but it often features infertility, firm testicular hypotrophy, hypergonadotropic hypogonadism, gynecomastia, and learning difficulties. Many other pathologies are associated with KS, but lipedema is never mentioned and there are no data in the literature linking these two pathologies. Observation: We report the cases of a 55-year-old man (146.8 kg, body mass index [BMI] 40.96 kg/m2) whose diagnosis of KS was known when hospitalized for lipedema, and of a 62-year-old man (198.1 kg, BMI 68.55 kg/m2) whose diagnosis of KS was made after the hospitalization for lipedema. Discussion: The concomitant presence of these two rare pathologies encourages the construction of an epidemiological study to support this association. It is also an element that can feed the research on the physiopathology of these two affections. Finally, the clinician must know how to suspect the possibility of lipedema in a patient with KS presenting an enlargement of the lower limbs and should know how to evoke a diagnosis of KS in front of a lipedema aspect in a man.

Olivier Cadart

Cyril Le Moal

Marie Michelet

Laurène Bosc

Emilie Pupier

Maud Monsaingeon-Henry

Blandine Gatta-Cherifi

Lipedema and Klinefelter Syndrome in Two Morbidly Obese Patients

两名病态肥胖患者中的脂肪水肿和克莱恩费尔特综合征

Objective: Hematocrit (HCT)/hemoglobin (Hb) ratio in (%/g/dL) is around 3, with high fidelity between measured and derived Hb (applying the conversion using HCT) in various pathologies. We examined changes in HCT and Hb values and HCT/Hb, compared with baseline, in men with adult-onset testosterone deficiency (TD) given testosterone therapy (TTh). Materials and Methods: Data were analyzed from an observational, prospective registry study at various time points in 353 men with adult-onset TD receiving testosterone undecanoate (median follow-up: 105 months). After establishing baseline HCT/Hb, we compared (cf. baseline) changes in HCT, Hb, and HCT/Hb at 12, 48, 72, and 96 months. Regression analyses determined predictors of HCT and Hb change. Results: TTh was associated with (p < 0.0001) increases in median HCT and Hb; 44% to 49% and 14.5 to 14.9 g/dL at final assessment, respectively. Regression analyses showed that HCT change was associated with baseline HCT and testosterone levels, while Hb change was associated with baseline Hb, HCT, and testosterone levels. In the total cohort and subgroups, HCT/Hb increased significantly at all time points (p < 0.0001, cf. baseline) with over 90% of men demonstrating increases. Linear regression showed that the ratio of HCT change/Hb change (i.e., difference between HCT at the various time points and baseline value/difference between Hb at the various time points and baseline value), following TTh at each time point was higher than the baseline HCT/Hb ratio. Conclusion: HCT increase was greater than we anticipated from the established HCT/Hb of 3. We speculate that increased erythrocyte life span with associated higher Hb loss via vesiculation could account for our observation. This could have a bearing when using HbA1c as an indicator in men with adult-onset TD on TTh.

Nathan Lorde

Amro Maarouf

Richard C. Strange

Carola S. König

Geoff Hackett

Ahmad Haider

Karim Sultan Haider

Pieter Desnerck

Farid Saad

Sudarshan Ramachandran

Testosterone Therapy in Adult-Onset Testosterone Deficiency: Hematocrit and Hemoglobin Changes

成年男性睾酮缺乏症的睾酮治疗：血细胞比容和血红蛋白的变化

Objective: Testosterone therapy (TTh) may reduce morbidity/mortality in men with adult-onset testosterone deficiency (TD), though some cardiovascular safety concerns remain. Increased hematocrit (HCT), a recognized effect of therapy, may be associated with cardiovascular disease and mortality. We examined HCT change (Δ) in men prescribed/not prescribed testosterone, and associations with mortality. Methods: We analyzed data from a prospective registry study with adult-onset TD patients: 353 men given testosterone undecanoate (TU) and 384 opting against TTh. Change in HCT after 12, 48, 72, and 96 months of TU and at final assessment was compared (nonparametric tests). The association between baseline HCT, Δ HCT, and mortality was studied using logistic and Cox regression. Results: HCT increased significantly (median change at final assessment: +5.0%) in men on TTh. HCT was higher (p = 0.021, rank-sum test) in those alive than in those who died, although median values were identical (49.0%). Baseline HCT and Δ HCT were inversely associated with mortality after adjustment for age in both logistic and Cox regression models. Men with final HCT >49.0% (median) suffered lower mortality than men with HCT ≤49.0%. Conclusions: A median HCT increase of 5.0% was associated with TTh, mostly within 48 months of commencing therapy. An increase in HCT (up to 52.0% at final assessment) was independently associated with reduced mortality, indicating current guidelines using a HCT value of 54.0% as a threshold for management change are appropriate until further study.

Adeeba Ahmed

Karim S. Haider

Testosterone Therapy: Increase in Hematocrit is Associated with Decreased Mortality

睾酮治疗：红细胞压积增加与死亡率降低相关

Testosterone acts on the brain and spinal cord as an important regulator of neural functions, either by binding to the androgen receptor (AR) or via its aromatization to estradiol. Neurons have long been considered as its primary cellular target, but testosterone also plays a key role in the formation of myelin within the central nervous system (CNS). Remarkable features of CNS myelin are its plasticity and great capacity of regeneration. After a demyelinating lesion, new myelin sheaths are formed by oligodendrocytes recently generated from oligodendrocyte progenitor cells or by spared mature oligodendrocytes. Testosterone has allowed to demonstrate strong remyelinating effects, mediated by the AR receptor, in mouse models of toxin-induced demyelination. Enhancing these regenerative responses has become an objective for the treatment of demyelinating diseases, possibly including testosterone or AR ligands.

Michael Schumacher

Abdelmoumen Ghoumari

Claudia Mattern

Pierre Bougnères

Elisabeth Traiffort

Testosterone and Myelin Regeneration in the Central Nervous System

睾酮与中枢神经系统髓鞘再生

Androgens: Clinical Research and TherapeuticsVol. 3, No. 1 EditorialOpen AccessCreative Commons licenseHypogonadotropic Hypogonadism in Diabesity: Pathogenic Factors and Therapeutic ImplicationsParesh Dandona, Sandeep Dhindsa, and Husam GhanimParesh Dandona*Address correspondence to: Paresh Dandona, BSc, MBBS, MD, DPhil, FRCP, Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo, 1000 Youngs Road, Suite 105, Williamsville, NY 14221, USA. E-mail Address: pdandona@kaleidahealth.orgDivision of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo, Williamsville, New York, USA.Search for more papers by this author, Sandeep Dhindsahttps://orcid.org/0000-0001-9342-9807Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo, Williamsville, New York, USA.Division of Endocrinology, Diabetes and Metabolism, Saint Louis University, St. Louis, Missouri, USA.Search for more papers by this author, and Husam GhanimDivision of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo, Williamsville, New York, USA.Search for more papers by this authorPublished Online:28 Dec 2022https://doi.org/10.1089/andro.2022.0019AboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail Hypogonadotropic hypogonadism (HH) was found to occur in 33% male patients with type 2 diabetes.1 These patients had low total and free testosterone concentrations with inappropriately low or normal luteinizing hormone (LH) and follicle-stimulating hormone (FSH) concentrations. Since the occurrence of hypogonadism was not related to either HbA1c or the duration of diabetes but to body mass index (BMI), a study in nondiabetic obese patients was carried out, which revealed a prevalence of HH in 25%.2 Thus, this is the commonest cause of hypogonadism in the community.These observations have added ∼18 million hypogonadal patients in the United States alone, based on the prevalence of type 2 diabetes and obesity. In a study comparing type 1 and type 2 diabetic patients, it was shown that the occurrence of HH was confined to type 2 diabetes.3 Since these observations were made in middle aged to older populations, a study in obese young males between 14 and 20 years of age was conducted.4 These patients were found to have similar prevalence of HH as reflected in the total and free testosterone, LH, and FSH concentrations.In these patients and older patients, testosterone concentrations were found to have an inverse relationship with BMI. Bariatric surgery with weight loss has been shown to raise testosterone concentrations. In the younger population with morbid obesity, the prevalence of HH was 75%.5 After bariatric surgery, testosterone levels normalized in the majority after 2 years and were maintained in those who maintained their weight loss but diminished again if they regained weight. Thus, body weight is a major determinant of plasma testosterone concentrations.It has also been demonstrated that diabetic patients with HH have increased insulin resistance when compared with those without.6 Testosterone patients restore insulin sensitivity as measured by Homeostatic Model Assessment of Insulin Resistance or euglycemic hyperinsulinemic clamps, while simultaneously reducing adiposity and increasing muscle mass. In HH patients, four genes in the insulin signaling pathway, insulin receptor β-subunit, IRS-1, Akt-2, and GLUT-4, had diminished expression. All four genes had normalized expression after testosterone replacement.Thus, testosterone is an insulin sensitizer.7 In addition, testosterone also increases the expression of activated protein kinase that induces an increase in glucose uptake independently of insulin signal transduction.8 Consistent with these observations, testosterone has been shown to prevent the development of diabetes in prediabetic patients, reverse prediabetes into a state of normality, and to reverse diabetes in 33% of patients with diabetes and HH for an 8-year period.9,10In addition to the mentioned effects, testosterone also increased the expression of the androgen receptor, the estrogen receptor, and aromatase, all of which are diminished in HH patients.11 Furthermore, testosterone also exerts anti-inflammatory effects that may be relevant to the inhibition of atherosclerosis and the control/prevention of infections.6 In this context, it is relevant that a very large retrospective study has shown that hypogonadal males have markedly increased cardiovascular mortality, whereas those hypogonadal patients whose testosterone had been replaced appropriately did not have such an increase.12Most recently, hypogonadal males have been shown to have two times higher incidence of hospitalization after COVID-19 infection, as compared with men with normal testosterone concentrations.13 This was independent of other known risk factors for hospitalization, such as age, comorbidities, immunosuppression, or body weight. Hypogonadal men with appropriate testosterone replacement did not experience an increase in these hospitalizations. Clearly, therefore, testosterone also has an anti-inflammatory effect that is clinically relevant.The most recent advance in HH and testosterone replacement was when obese males with either impaired glucose tolerance or early diabetes with testosterone concentrations <400 ng/dL were treated with depot testosterone 1000 mg every 3 months in addition to lifestyle change.14 The control arm was subjected to lifestyle change only with placebo injections. It was observed that plasma glucose concentrations fell, and diabetes was reversed in 21.1% of patients on testosterone as compared with 12.4% on lifestyle alone.There was a decrease in 2 h glucose by 31 mg/dL in the testosterone arm and 17 mg/dL in the control arm. Among the prediabetic patients, 7.6% patients progressed to diabetes in the testosterone arm, whereas 14.9% progressed to diabetes in the control arm. Among the early type 2 diabetic patients, there was a reversal of diabetes in 45.2% in the testosterone arm and only 32.1% in the control arm. In addition, there was a significantly greater reduction in waist circumference, total, and abdominal adiposity in the testosterone arm when compared with the control arm.Furthermore, there was an increase in total and arm muscle mass and the strength of the muscles in the nondominant hand. This large prospectively randomized study confirmed the previous observations in patients who had low normal rather than subnormal testosterone concentrations,14 as already discussed.6,7 An Austrian study has also recently confirmed a relationship between testosterone and insulin sensitivity and related metabolic indices in prediabetic males.15 Clearly, therefore, HH predisposes individuals to an insulin-resistant state and testosterone restores insulin sensitivity and can potentially reverse type 2 diabetes and prediabetes.6,15–17In conclusion, testosterone needs to be measured in all type 2 diabetes and obese patients, and if the concentrations are low, testosterone replacement has to be considered not only for its effects on sexual function but also for its metabolic effects that are profound and widespread.Author Disclosure StatementP.D. receives research support from National Institutes of Health; JDRF, ADA; Novo Nordisk; Bristol Meyer Squibb; AbbVie Pharmaceuticals; and Astra Zeneca, Boehringer Ingelheim Pharmaceuticals and honorarium from Eli Lilly; Novartis; GlaxoSmithKline; Merck; Novo Nordisk; Takeda; and Sanofi-Aventis. S.D. is a consultant for Bayer, Clarus Therapeutics. H.G. has no disclosures.Funding InformationThis study was supported by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (R01 grant to PD; R01DK075877).References1. Dhindsa S, Prabhakar S, Sethi M, et al. Frequent occurrence of hypogonadotropic hypogonadism in type 2 diabetes. J Clin Endocrinol Metab 2004;89(11):5462–5468; doi: 10.1210/jc.2004-0804 Crossref, Medline, Google Scholar2. Dhindsa S, Miller MG, McWhirter CL, et al. Testosterone concentrations in diabetic and nondiabetic obese men. Diabetes Care 2010;33(6):1186–1192; doi: 10.2337/dc09-1649 Crossref, Medline, Google Scholar3. Tomar R, Dhindsa S, Chaudhuri A, et al. Contrasting testosterone concentrations in type 1 and type 2 diabetes. Diabetes Care 2006;29(5):1120–1122; doi: 10.2337/diacare.2951120 Crossref, Medline, Google Scholar4. Chandel A, Dhindsa S, Topiwala S, et al. Testosterone concentration in young patients with diabetes. Diabetes Care 2008;31(10):2013–2017; doi: 10.2337/dc08-0851 Crossref, Medline, Google Scholar5. Dhindsa S, Ghanim H, Jenkins T, et al. High prevalence of subnormal testosterone in obese adolescent males: Reversal with bariatric surgery. Eur J Endocrinol 2022;186(3):319–327; doi: 10.1530/EJE-21-0545 Crossref, Medline, Google Scholar6. Dhindsa S, Ghanim H, Batra M, et al. Insulin resistance and inflammation in hypogonadotropic hypogonadism and their reduction after testosterone replacement in men with type 2 diabetes. Diabetes Care 2016;39(1):82–91; doi: 10.2337/dc15-1518 Crossref, Medline, Google Scholar7. Dandona P, Dhindsa S, Ghanim H, et al. Mechanisms underlying the metabolic actions of testosterone in humans: A narrative review. Diabetes Obes Metab; 2021;23(1):18–28; doi: 10.1111/dom.14206 Crossref, Medline, Google Scholar8. Ghanim H, Dhindsa S, Batra M, et al. Testosterone increases the expression and phosphorylation of AMP kinase alpha in men with hypogonadism and type 2 diabetes. J Clin Endocrinol Metab 2020;105(4); doi: 10.1210/clinem/dgz288 Crossref, Google Scholar9. Haider KS, Haider A, Saad F, et al. Remission of type 2 diabetes following long-term treatment with injectable testosterone undecanoate in patients with hypogonadism and type 2 diabetes: 11-year data from a real-world registry study. Diabetes Obes Metab 2020;22(11):2055–2068; doi: 10.1111/dom.14122 Crossref, Medline, Google Scholar10. Yassin A, Haider A, Haider KS, et al. Testosterone therapy in men with hypogonadism prevents progression from prediabetes to type 2 diabetes: Eight-year data from a registry study. Diabetes Care 2019;42(6):1104–1111; doi: 10.2337/dc18-2388 Crossref, Medline, Google Scholar11. Ghanim H, Dhindsa S, Abuaysheh S, et al. Diminished androgen and estrogen receptors and aromatase levels in hypogonadal diabetic men: Reversal with testosterone. Eur J Endocrinol 2018;178(3):277–283; doi: 10.1530/EJE-17-0673 Crossref, Medline, Google Scholar12. Sharma R, Oni OA, Gupta K, et al. Normalization of testosterone level is associated with reduced incidence of myocardial infarction and mortality in men. Eur Heart J 2015;36(40):2706–2715; doi: 10.1093/eurheartj/ehv346 Crossref, Medline, Google Scholar13. Dhindsa S, Champion C, Deol E, et al. Association of male hypogonadism with risk of hospitalization for COVID-19. JAMA Netw Open 2022;5(9):e2229747; doi: 10.1001/jamanetworkopen.2022.29747 Crossref, Medline, Google Scholar14. Wittert G, Bracken K, Robledo KP, et al. Testosterone treatment to prevent or revert type 2 diabetes in men enrolled in a lifestyle programme (T4DM): A randomised, double-blind, placebo-controlled, 2-year, phase 3b trial. Lancet Diabetes Endocrinol 2021;9(1):32–45; doi: 10.1016/S2213-8587(20)30367-3 Crossref, Medline, Google Scholar15. Leutner M, Matzhold C, Bellach L, et al. Increase in testosterone levels is related to a lower risk of conversion of prediabetes to manifest diabetes in prediabetic males. Wien Klin Wochenschr 2022;134(1–2):1–6; doi: 10.1007/s00508-021-01903-1 Crossref, Medline, Google Scholar16. Yeap BB, Wittert GA. Testosterone, diabetes risk, and diabetes prevention in men. Endocrinol Metab Clin North Am 2022;51(1):157–172; doi: 10.1016/j.ecl.2021.11.004 Crossref, Medline, Google Scholar17. Jenkins CR, Rittel A, Sturdivant RX, et al. Glycemic benefits with adherence to testosterone therapy in men with hypogonadism and type 2 diabetes mellitus. Andrology 2021;9(4):1076–1085; doi: 10.1111/andr.12990 Crossref, Medline, Google ScholarCite this article as: Dandona P, Dhindsa S, Ghanim H (2022) Hypogonadotropic hypogonadism in diabesity: pathogenic factors and therapeutic implications, Androgens: Clinical Research and Therapeutics 3.1, 214–216, DOI: 10.1089/andro.2022.0019.Abbreviations UsedBMIbody mass indexFSHfollicle-stimulating hormoneHHhypogonadotropic hypogonadismLHluteinizing hormoneFiguresReferencesRelatedDetails Volume 3Issue 1Dec 2022 Information© Paresh Dandona et al., 2022; Published by Mary Ann Liebert, Inc.To cite this article:Paresh Dandona, Sandeep Dhindsa, and Husam Ghanim.Hypogonadotropic Hypogonadism in Diabesity: Pathogenic Factors and Therapeutic Implications.Androgens: Clinical Research and Therapeutics.Dec 2022.214-216.http://doi.org/10.1089/andro.2022.0019creative commons licensePublished in Volume: 3 Issue 1: December 28, 2022Open accessThis Open Access article is distributed under the terms of the Creative Commons License [CC-BY] ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.PDF download

Paresh Dandona

Sandeep Dhindsa

Husam Ghanim

Hypogonadotropic Hypogonadism in Diabesity: Pathogenic Factors and Therapeutic Implications

糖尿病性肥胖中的低促性腺激素性性腺功能减退症：发病机制因素与治疗意义

Introduction: Anabolic–androgenic steroids (AASs) are commonly used by both professional and amateur athletes to improve strength, muscle mass, and physical appearance. Aims: Scientific data on the adverse effects of AASs are scarce and there is little place for the subject in medical curricula. This may lead to a lack of knowledge and distrusting attitudes of physicians toward AAS users. The aim of this case series is to illustrate how these issues may lead to diagnostic delay and to make a plea for better education on the topic. Case Description: We describe three patients who attended our outpatient AAS clinic with azoospermia, gynecomastia, and hypogonadism, respectively. After referral to the appropriate specialist, symptoms were wrongly appreciated, sometimes despite our medical recommendations, and patients did not receive the necessary additional investigations or treatment in a timely manner. Discussion: Diagnostic delay in the presented cases was the result of inexperience with the subject and unfamiliarity with health effects of AASs. Prejudice and stigmatization may lead to a tendency to wait, and a reluctance to help, (former) AAS users. Conclusion: All patients and substance abusers, including AAS users, should be treated equally, despite the cause of their illness. Diagnostic delay can be prevented with an unbiased attitude and improved education.

Maartje A.J. Rops

Diederik L. Smit

Willem de Ronde

Bias Among Health Care Professionals: How Prejudice Leads to Diagnostic Delay in Patients Using Anabolic–Androgenic Steroids

医疗专业人员中的偏见：偏见如何导致使用合成代谢-雄激素类固醇患者的诊断延迟

Androgen deprivation therapy is a mainstay of advanced prostate cancer (PCa) but the resulting low testosterone levels leave men susceptible to a multitude of adverse effects. These can include vasomotor symptoms, reduced sexual desire and performance, and mood changes. Testosterone therapy (TTh) in advanced PCa has historically been contraindicated since Huggins and Hodges reported that testosterone activates PCa. Although TTh has been demonstrated to be safe in patients who have undergone treatment for localized PCa, there is extremely limited evidence on its safety in advanced PCa. Despite the lack of evidence, some men with advanced PCa still inquire about TTh, and recent publications have described its use. In this article, we review the potential implications of TTh in men with advanced PCa, defined here as biochemical recurrence after localized therapy or metastatic PCa that is either hormone sensitive or castration resistant.

Emily Chedrawe

Aditya Sathe

Josh White

Testosterone Therapy in Advanced Prostate Cancer

晚期前列腺癌中的睾酮治疗

Purpose: Oral and injectable testosterone replacement therapies have been reported to increase blood pressure (BP) in hypogonadal men. Less is known about the effects of topical testosterone formulations on BP. Materials and Methods: We studied the effects of a new oral testosterone undecanoate (TU) (Kyzatrex™) and a topical testosterone gel (Androgel™) on BP and heart rate, in a 2:1 randomized trial of men with hypogonadism. Digital BPs and clinical assessments were obtained at baseline and at 90, 180 and 365 days. Results: There were 314 men randomized (mean age 49.7 years, 82% white, and 35% with treated hypertension). The mean changes from baseline in systolic BP were 2.2 mmHg (95% confidence interval [CI] 0.6–3.7) on the oral TU and 3.1 mmHg (95% CI 1.0–5.1) on the topical testosterone at 90 days. Similar findings were seen after 180 and 365 days. Heart rate increased by 4.3 and 2.7 beats/min at 90 days on oral and topical testosterone, respectively. For those men with treated hypertension, changes in systolic BP in the oral TU group were higher compared with those without hypertension, whereas those on topical testosterone had similar increases in systolic BP regardless of hypertension status. Outlier analyses for systolic BP at 90 days demonstrated a higher proportions of subjects with increases of 5 and 10 mmHg postbaseline on topical testosterone gel versus this oral TU. Conclusions: These data demonstrate that the overall effects of the oral TU on BP were comparable with a topical testosterone. In men without hypertension, the oral TU induced smaller changes in BP compared with topical testosterone. Clinical Trial Registration (https://www.clinicaltrials.gov/): NCT04467697.

William B. White

James S. Bernstein

Abraham Morgentaler

Om Dhingra

Effects of Oral Testosterone Undecanoate (Kyzatrex) Versus Testosterone Gel (Androgel) on Long-Term (to 12 Months) Blood Pressure Levels

口服十一酸睾酮（Kyzatrex）与睾酮凝胶（Androgel）对长期（至12个月）血压水平的影响

The objective of this study was to determine the rates of hypogonadism and prescription of testosterone replacement therapy (TRT) in men with Klinefelter syndrome (KS). We hypothesized that men with KS are under-treated for testosterone deficiency with TRT due to a combination of factors, including a poor understanding of hypogonadism in this population and neurocognitive issues leading to delay in seeking of treatment for hypogonadism.We queried TriNetX, a large multicenter electronic health record database, to identify all men with a diagnosis of KS (ICD-10-CM Q98.4). Prevalence of testosterone deficiency was determined as defined by testosterone level < 300 ng/dL. The primary outcome of the study was prescription of any of the following forms of TRT on the day of diagnosis or later.There were in total 5437 men with diagnosis of KS. A total of 1581 men with KS received laboratory measurement of testosterone level, 1113 (70.4%) of whom were hypogonadal. Mean testosterone level in this group was 354 ng/dL [50-658]. Of the 1113 men found to be hypogonadal, only 657 (59.0%) men were given prescription for TRT.This is the first study to evaluate TRT prescribing habits in men with KS. In this large retrospective study, TRT was underprescribed in men with KS. Further studies are needed to corroborate these findings and to evaluate barriers to receiving care in this population.

Chase Carto

Justin Loloi

Katherine Campbell

Testosterone Therapy in Men with Klinefelter Syndrome: Analysis of a Global Federated Research Network

克氏综合征男性睾酮治疗：全球联合研究网络分析

Publication Information	Publisher: Mary Ann Liebert Inc.，Publishing cycle: ，Journal Type: journal，Open Access Journals: No
Basic data	Year of publication: 2020，Proportion of original research papers: 0.00%，Self Citation Rate:N.A.， Gold OA Rate: 0.00%
Average review cycle	网友分享经验：8 Weeks

Androgens

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