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Siltari A, Murtola TJ, Kausz J, Talala K, Taari K, Tammela TL, Auvinen A. Testosterone replacement therapy is not associated with increased prostate cancer incidence, prostate cancer-specific, or cardiovascular disease-specific mortality in Finnish men. Acta Oncol 2023; 62:1898-1904. [PMID: 37971326 DOI: 10.1080/0284186x.2023.2278189] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2023] [Accepted: 10/28/2023] [Indexed: 11/19/2023]
Abstract
BACKGROUND Concerns have been expressed over the safety of testosterone replacement therapy (TRT) in men with late-onset hypogonadism (LOH). Previous studies have shown controversial results regarding the association of TRT with the risk of cardiovascular events or prostate cancer (PCa) incidence, aggressiveness, and mortality. This study explores the overall risk of PCa and risk by tumor grade and stage, as well as mortality from PCa and cardiovascular disease (CVD), among men treated with TRT compared to men without LOH and TRT use. MATERIALS AND METHODS The study included 78,615 men of age 55-67 years at baseline from the Finnish Randomized Study of Screening for Prostate Cancer (FinRSPC). Follow-up started at randomization and ended at death, emigration, or a common closing date January 1st, 2017. Cox proportional hazards regression model with time-dependent variables and adjustment for age, trial arm, use of other medications, and Charlson comorbidity index was used. Comprehensive information on TRT purchases during 1995-2015 was obtained from the Finnish National Prescription Database. PCa cases were identified from the Finnish Cancer Registry and causes of death obtained from Statistics Finland. RESULTS Over the course of 18 years of follow-up, 2919 men were on TRT, and 285 PCa cases were diagnosed among them. TRT users did not exhibit a higher incidence or mortality rate of PCa compared to non-users. On the contrary, men using TRT had lower PCa mortality than non-users (HR = 0.52; 95% CI 0.3-0.91). Additionally, TRT users had slightly lower CVD and all-cause mortality compared to non-users (HR = 0.87; 95% CI 0.75-1.01 and HR = 0.93; 95% CI 0.87-1.0, respectively). No time- or dose-dependency of TRT use was evident in any of the analyses. CONCLUSION Men using TRT were not associated to increased risk for PCa and did not experience increased PCa- or CVD-specific mortality compared to non-users. Further studies considering blood testosterone levels are warranted.
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Affiliation(s)
- Aino Siltari
- Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
- Faculty of Medicine, Pharmacology, University of Helsinki, Helsinki, Finland
| | - Teemu J Murtola
- Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
- Department of Urology, Tampere University Hospital, Tampere, Finland
| | - Josefina Kausz
- Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
| | | | - Kimmo Taari
- Department of Urology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Teuvo Lj Tammela
- Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
- Department of Urology, Tampere University Hospital, Tampere, Finland
| | - Anssi Auvinen
- Tampere University, Faculty of Social Sciences, Tampere, Finland
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2
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Zolla L, Ceci M. Plasma Metabolomics Profile of "Insulin Sensitive" Male Hypogonadism after Testosterone Replacement Therapy. Int J Mol Sci 2022; 23:ijms23031916. [PMID: 35163837 PMCID: PMC8836772 DOI: 10.3390/ijms23031916] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2022] [Revised: 01/28/2022] [Accepted: 02/03/2022] [Indexed: 01/27/2023] Open
Abstract
Male hypogonadism is a disorder characterized by low levels of testosterone, but patients can either show normal insulin (insulin-sensitive (IS)) or over time they can become insulin-resistant (IR). Since the two groups showed different altered metabolisms, testosterone replacement therapy (TRT) could achieve different results. In this paper, we analyzed plasma from 20 IS patients with low testosterone (<8 nmol/L) and HOMAi < 2.5. The samples, pre- and post-treatment with testosterone for 60 days, were analyzed by UHPLC and mass spectrometry. Glycolysis was significantly upregulated, suggesting an improved glucose utilization. Conversely, the pentose phosphate pathway was reduced, while the Krebs cycle was not used. Branched amino acids and carnosine metabolism were positively influenced, while β-oxidation of fatty acids (FFA) was not activated. Cholesterol, HDL, and lipid metabolism did not show any improvements at 60 days but did so later in the experimental period. Finally, both malate and glycerol shuttle were reduced. As a result, both NADH and ATP were significantly lower. Interestingly, a significant production of lactate was observed, which induced the activation of the Cori cycle between the liver and muscles, which became the main source of energy for these patients without involving alanine. Thus, the treatment must be integrated with chemicals which are not restored in order to reactivate energy production.
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3
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Alemany M. Estrogens and the regulation of glucose metabolism. World J Diabetes 2021; 12:1622-1654. [PMID: 34754368 PMCID: PMC8554369 DOI: 10.4239/wjd.v12.i10.1622] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2021] [Revised: 03/10/2021] [Accepted: 04/14/2021] [Indexed: 02/06/2023] Open
Abstract
The main estrogens: estradiol, estrone, and their acyl-esters have been studied essentially related to their classical estrogenic and pharmacologic functions. However, their main effect in the body is probably the sustained control of core energy metabolism. Estrogen nuclear and membrane receptors show an extraordinary flexibility in the modulation of metabolic responses, and largely explain gender and age differences in energy metabolism: part of these mechanisms is already sufficiently known to justify both. With regard to energy, the estrogen molecular species act essentially through four key functions: (1) Facilitation of insulin secretion and control of glucose availability; (2) Modulation of energy partition, favoring the use of lipid as the main energy substrate when more available than carbohydrates; (3) Functional protection through antioxidant mechanisms; and (4) Central effects (largely through neural modulation) on whole body energy management. Analyzing the different actions of estrone, estradiol and their acyl esters, a tentative classification based on structure/effects has been postulated. Either separately or as a group, estrogens provide a comprehensive explanation that not all their quite diverse actions are related solely to specific molecules. As a group, they constitute a powerful synergic action complex. In consequence, estrogens may be considered wardens of energy homeostasis.
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Affiliation(s)
- Marià Alemany
- Faculty of Biology, University of Barcelona, Barcelona 08028, Catalonia, Spain
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Gariani K, Jornayvaz FR. Pathophysiology of NASH in endocrine diseases. Endocr Connect 2021; 10:R52-R65. [PMID: 33449917 PMCID: PMC7983516 DOI: 10.1530/ec-20-0490] [Citation(s) in RCA: 45] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2020] [Accepted: 01/06/2021] [Indexed: 12/15/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the industrialized world. NAFLD encompasses a whole spectrum ranging from simple steatosis to nonalcoholic steatohepatitis (NASH) and cirrhosis. The latter can lead to hepatocellular carcinoma. Furthermore, NASH is the most rapidly increasing indication for liver transplantation in western countries and therefore represents a global health issue. The pathophysiology of NASH is complex and includes multiple parallel hits. NASH is notably characterized by steatosis as well as evidence of hepatocyte injury and inflammation, with or without fibrosis. NASH is frequently associated with type 2 diabetes and conditions associated with insulin resistance. Moreover, NASH may also be found in many other endocrine diseases such as polycystic ovary syndrome, hypothyroidism, male hypogonadism, growth hormone deficiency or glucocorticoid excess, for example. In this review, we will discuss the pathophysiology of NASH associated with different endocrinopathies.
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Affiliation(s)
- Karim Gariani
- Service of Endocrinology, Diabetes, Nutrition and Therapeutic Patient Education, Geneva University Hospitals and Geneva University, Geneva, Switzerland
| | - François R Jornayvaz
- Service of Endocrinology, Diabetes, Nutrition and Therapeutic Patient Education, Geneva University Hospitals and Geneva University, Geneva, Switzerland
- Diabetes Center, Faculty of Medicine, University of Geneva, Geneva, Switzerland
- Correspondence should be addressed to F R Jornayvaz:
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5
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Song SH, Byun SS. Polygenic risk score for genetic evaluation of prostate cancer risk in Asian populations: A narrative review. Investig Clin Urol 2021; 62:256-266. [PMID: 33943048 PMCID: PMC8100017 DOI: 10.4111/icu.20210124] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2021] [Revised: 04/15/2021] [Accepted: 04/15/2021] [Indexed: 12/16/2022] Open
Abstract
Decreasing costs of genetic testing and interest in disease inheritance has changed the landscape of cancer prediction in prostate cancer (PCa), and guidelines now include genetic testing for high-risk groups. Familial and hereditary PCa comprises approximately 20% and 5% of all PCa, respectively. Multifaceted disorders like PCa are caused by a combinatory effect of rare genes of high penetrance and smaller genetic variants of relatively lower effect size. Polygenic risk score (PRS) is a novel tool utilizing PCa-associated single nucleotide polymorphisms (SNPs) identified from genome-wide association study (GWAS) to generate an additive estimate of an individual's lifetime genetic risk for cancer. However, most PRS are developed based on GWAS collected from mainly European populations and do not address ethnic differences in PCa genetics. This review highlights the attempts to generate a PRS tailored to Asian males including data from Korea, China, and Japan, and discuss the clinical implications for prediction of early onset and aggressive PCa.
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Affiliation(s)
- Sang Hun Song
- Department of Urology, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Seok Soo Byun
- Department of Urology, Seoul National University Bundang Hospital, Seongnam, Korea.,Department of Medical Device Development, Seoul National University College of Medicine, Seoul, Korea.
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6
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Song SH, Kim JK, Lee H, Lee S, Hong SK, Byun SS. A single-center long-term experience of active surveillance for prostate cancer: 15 years of follow-up. Investig Clin Urol 2020; 62:32-38. [PMID: 33258324 PMCID: PMC7801164 DOI: 10.4111/icu.20200206] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2020] [Revised: 06/29/2020] [Accepted: 07/17/2020] [Indexed: 12/01/2022] Open
Abstract
Purpose To describe a single-center 15-year experience of active surveillance (AS) for prostate cancer (PCa). Materials and Methods We retrospectively reviewed patients who underwent AS between 2003 and 2018. One hundred fifty-three patients were selected according to the following criteria: (1) biopsy Gleason pattern ≤3+4 with (2) ≤two positive core(s) and (3) ≤50% core involvement, clinical-stage ≤T2a, and prostate-specific antigen (PSA) ≤20 ng/mL. Follow-up included PSA measurement every six months, prostate biopsies at one year and then every 2–3 years, and MRI every year. Intervention was triggered by (1) Gleason score (GS) upgrading, (2) >two positive cores, or (3) PSA doubling-time in <3 years. Results Mean (±standard deviation) follow-up was 36.4 (±31.9) months. Ninety-three (60.8%) and 20 (13.1%) patients received second and third biopsies, respectively. Seventy-two patients (47.1%) discontinued AS for various reasons (59, intervention; 13, follow-up loss). Reasons for intervention consisted of GS upgrading (42.4%), >two positive cores (8.5%), abnormal PSA kinetics (11.9%), and patient preference (37.3%). Notably, 12 (25.5%) patients had pathologic GS ≥4+3 (unfavorable disease) and 3 (6.4%) patients had pathologic stage ≥T3a at radical prostatectomy. Median time to treatment-free survival was 19.5 months. Of the 59 patients who switched to intervention, biochemical recurrence was reported in only one (0.7%) patient. Conclusions AS is an available option for low-risk PCa in carefully selected patients. Further larger prospective studies are needed to determine the optimal criteria for AS, especially in Korean PCa patients.
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Affiliation(s)
- Sang Hun Song
- Department of Urology, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Jung Kwon Kim
- Department of Urology, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Hakmin Lee
- Department of Urology, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Sangchul Lee
- Department of Urology, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Sung Kyu Hong
- Department of Urology, Seoul National University Bundang Hospital, Seongnam, Korea.,Department of Urology, Seoul National University College of Medicine, Seoul, Korea
| | - Seok Soo Byun
- Department of Urology, Seoul National University Bundang Hospital, Seongnam, Korea.,Department of Urology, Seoul National University College of Medicine, Seoul, Korea.
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Yuan X, Shen J, Zhang X, Tu W, Fu Z, Jin Y. Imidacloprid disrupts the endocrine system by interacting with androgen receptor in male mice. THE SCIENCE OF THE TOTAL ENVIRONMENT 2020; 708:135163. [PMID: 31780179 DOI: 10.1016/j.scitotenv.2019.135163] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/29/2019] [Revised: 10/16/2019] [Accepted: 10/23/2019] [Indexed: 06/10/2023]
Abstract
In the current study, six-week-old male ICR mice were administered imidacloprid (IMI) at concentrations of 3, 10 and 30 mg/L for a duration of 10 weeks to investigate the toxicity of IMI on the endocrine system. We observed that testicular morphology was severely impaired and damaged, and the levels of serum testosterone (T) and the expression of androgen receptor (AR) decreased significantly. Molecular docking analysis suggested that IMI docks into the active site of AR successfully and that three key hydrogen bonds were formed with the active site residues Glu11, Gln41 and Lys138. The binding free energy value of the AR-IMI complex suggested a stable binding between IMI and AR. All these results indicated that IMI could interact with AR. In addition, major genes in the testis involved in the synthesis of cholesterol and T were generally inhibited, and the serum cholesterol sources were also reduced. Moreover, the aromatase in male mice was lacking after subchronic IMI exposure. The data acquired from the present study indicated that IMI could lead to endocrine disruption by interacting with AR and influence the expression of genes involved in the production of T in male mice.
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Affiliation(s)
- Xianling Yuan
- College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China
| | - Jiayan Shen
- College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China
| | - Xinyue Zhang
- College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China
| | - Wenqing Tu
- Research Institute of Poyang Lake, Jiangxi Academy of Sciences, Nanchang 330029, China
| | - Zhengwei Fu
- College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China
| | - Yuanxiang Jin
- College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China.
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8
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Li D, Li X, Peng E, Liao Z, Tang Z. Do Urologists Really Recognize the Association Between Erectile Dysfunction and Cardiovascular Disease? Sex Med 2020; 8:195-204. [PMID: 32007471 PMCID: PMC7261682 DOI: 10.1016/j.esxm.2019.12.002] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2019] [Revised: 11/06/2019] [Accepted: 12/30/2019] [Indexed: 12/25/2022] Open
Abstract
INTRODUCTION Erectile dysfunction (ED) and cardiovascular diseases (CVDs) share many common risk factors. ED could be a strong independent predictive factor of CVDs. Furthermore, the treatment of ED had been shown to be beneficial for cardiovascular diseases. However, the association between ED and CVDs has been reported scarcely in the literature. AIM To investigate urologists' perception, diagnosis, and treatment of CVDs in patients with ED. METHODS The study was conducted as a prospective study from November 2018 through February 2019, including urologists aged 18-64 years. All participants completed a survey of the knowledge of ED via an online questionnaire platform in 7 WeChat groups of urologists. WeChat is the most popular multipurpose messaging and social media in China. MAIN OUTCOME MEASURE The main outcomes were the answers that urologists chose or filled. RESULTS 449 urologists were included. Most of participants (375, 83.5%) agreed that CVDs are associated with ED. Only 231 participants (51.4%) thought ED was an independent disorder. The awareness of the association between ED and CVDs is significantly higher among male urologists than their female counterparts. Although 378 (83.6%) participants believed that the progression of these 2 diseases was consistent, only 181 (44.9%) would do conjoined assessment of both CVDs and ED. In addition, most urologists only considered conventional treatment, such as psychological intervention (341, 75.4%) and phosphodiesterase type 5 inhibitor (PDE5i) therapy (318, 70.4%) for their patients, whereas 339 urologists (88.3%) claimed that they would treat CVDs in patients with both ED and CVDs. 344 (76.6%) urologists showed some concerns over PDE5is. CONCLUSION Urologists' assessment of CVDs in patients with ED was disappointing especially among young and female urologists or those working in underserved areas. Besides, the urologists' treatments of ED were not updated, and their attitudes toward the safety and effectiveness of PDE5is for CVDs were not optimistic. Li D, Li X, Peng A, et al. Do Urologists Really Recognize the Association Between Erectile Dysfunction and Cardiovascular Disease? Sex Med 2020;8:195-204.
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Affiliation(s)
- Dongjie Li
- Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, Hunan, China; Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, Hunan, China; Department of Geriatric urology, Xiangya International Medical Center, Xiangya Hospital, Central South University, Changsha, China; National Clinical Research Center for Geriatric Disorders, Changsha, China
| | - Xiucheng Li
- Department of Urology, Xiangya Hospital, Central South University, Changsha, China
| | - Emin Peng
- Department of Geriatric urology, Xiangya International Medical Center, Xiangya Hospital, Central South University, Changsha, China
| | - Zhangcheng Liao
- Department of Urology, Xiangya Hospital, Central South University, Changsha, China
| | - Zhengyan Tang
- National Clinical Research Center for Geriatric Disorders, Changsha, China; Department of Urology, Xiangya Hospital, Central South University, Changsha, China.
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9
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Molina-Vega M, Asenjo-Plaza M, García-Ruiz MC, Varea-Marineto E, Casal-Nievas N, Álvarez-Millán JJ, Cabezas-Sanchez P, Cardona-Díaz F, Queipo-Ortuño MI, Castellano-Castillo D, Tinahones FJ, Fernández-García JC. Cross-Sectional, Primary Care-Based Study of the Prevalence of Hypoandrogenemia in Nondiabetic Young Men with Obesity. Obesity (Silver Spring) 2019; 27:1584-1590. [PMID: 31411814 DOI: 10.1002/oby.22579] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2019] [Accepted: 06/11/2019] [Indexed: 01/18/2023]
Abstract
OBJECTIVE Obesity-associated hypoandrogenemia is increasing in parallel to the obesity epidemic. The prevalence of hypoandrogenemia in nondiabetic young men with obesity is not known. This study aimed to evaluate the prevalence of hypoandrogenemia and associated risk factors in this population. METHODS This cross-sectional study included 266 nondiabetic men < 50 years of age with obesity who were referred from primary care. Total testosterone (high-performance liquid chromatography mass spectrometry), sex hormone-binding globulin, free testosterone (FT), luteinizing hormone (LH), high-sensitivity C-reactive protein, and homeostatic model assessment of insulin resistance were determined. Body composition and erectile function were also assessed. Hypoandrogenemia was defined as FT level < 70 pg/mL. RESULTS Subnormal FT concentrations were found in 25.6% of participants. Hypoandrogenemia prevalence was different along the BMI continuum, being > 75% in individuals with BMI ≥ 50 kg/m2 . A multivariate regression analysis indicated that increasing BMI (P < 0.001), age (P = 0.049), and reduced LH levels (P = 0.003) were independent risk factors for hypoandrogenemia. CONCLUSIONS In a primary care-based cohort of nondiabetic young men with obesity, hypoandrogenemia was a very prevalent finding and was directly associated with adiposity. Obesity, age, and reduced LH levels were independent risk factors associated with hypoandrogenemia. Further prospective studies are needed to evaluate the long-term consequences of hypoandrogenemia in this population.
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Affiliation(s)
- María Molina-Vega
- Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, Malaga, Spain
- Instituto de Investigación Biomédica de Málaga-IBIMA, Malaga, Spain
- Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain
| | | | | | | | | | | | | | - Fernando Cardona-Díaz
- Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, Malaga, Spain
- Instituto de Investigación Biomédica de Málaga-IBIMA, Malaga, Spain
- Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain
| | - María Isabel Queipo-Ortuño
- Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, Malaga, Spain
- Instituto de Investigación Biomédica de Málaga-IBIMA, Malaga, Spain
- Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain
- Department of Medical Oncology, Virgen de la Victoria University Hospital, Malaga, Spain
| | - Daniel Castellano-Castillo
- Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, Malaga, Spain
- Instituto de Investigación Biomédica de Málaga-IBIMA, Malaga, Spain
- Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain
| | - Francisco J Tinahones
- Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, Malaga, Spain
- Instituto de Investigación Biomédica de Málaga-IBIMA, Malaga, Spain
- Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain
| | - José C Fernández-García
- Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, Malaga, Spain
- Instituto de Investigación Biomédica de Málaga-IBIMA, Malaga, Spain
- Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain
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10
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Testosterone Deficiency and Endothelial Dysfunction: Nitric Oxide, Asymmetric Dimethylarginine, and Endothelial Progenitor Cells. Sex Med Rev 2019; 7:661-668. [DOI: 10.1016/j.sxmr.2019.02.005] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2018] [Revised: 02/12/2019] [Accepted: 02/13/2019] [Indexed: 12/15/2022]
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11
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Wu J, Dai F, Li C, Zou Y. Gender Differences in Cardiac Hypertrophy. J Cardiovasc Transl Res 2019; 13:73-84. [PMID: 31418109 DOI: 10.1007/s12265-019-09907-z] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2019] [Accepted: 08/06/2019] [Indexed: 12/17/2022]
Abstract
Cardiac hypertrophy is an adaptive response to abnormal physiological and pathological stimuli, which can be classified into concentric and eccentric hypertrophy, induced by pressure overload or volume overload, respectively. In both physiological and pathological scenarios, females generally show a more favorable form of hypertrophy compared with their male counterparts. However once established, cardiac hypertrophy is a stronger risk factor for heart failure in females. Pre-menopausal women are better protected against cardiac hypertrophy compared with men, but this protection is abolished following menopause and is partially restored after estrogen replacement therapy. Estrogen exerts its protection by counteracting pro-hypertrophy signaling pathways, whereas androgen mostly plays an opposite role in cardiac hypertrophy. We here summarize the progress in the understanding of sexual dimorphisms in cardiac hypertrophy and highlight recent breakthroughs in the regulatory role of sex hormones and their intricate molecular networks, in order to shed light on gender-oriented therapeutic efficacy for pathological hypertrophy.
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Affiliation(s)
- Jian Wu
- Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital and Institutes of Biomedical Sciences, Fudan University, 180 Feng Lin Road, Shanghai, 200032, China.
| | - Fangjie Dai
- Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital and Institutes of Biomedical Sciences, Fudan University, 180 Feng Lin Road, Shanghai, 200032, China
| | - Chang Li
- Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital and Institutes of Biomedical Sciences, Fudan University, 180 Feng Lin Road, Shanghai, 200032, China
| | - Yunzeng Zou
- Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital and Institutes of Biomedical Sciences, Fudan University, 180 Feng Lin Road, Shanghai, 200032, China.
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12
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Lee HY, Park S, Doo SW, Yang WJ, Song YS, Kim JH. Trends in Prostate Cancer Prevalence and Radical Prostatectomy Rate according to Age Structural Changes in South Korea between 2005 and 2015. Yonsei Med J 2019; 60:257-266. [PMID: 30799588 PMCID: PMC6391527 DOI: 10.3349/ymj.2019.60.3.257] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2018] [Revised: 01/22/2019] [Accepted: 01/24/2019] [Indexed: 12/11/2022] Open
Abstract
PURPOSE Radical prostatectomy (RP) is one of main treatments for prostate cancer (Pca). The prevalence of Pca has been decreasing in recent reports. However, no study has reported trends in Pca prevalence or RP rate according to age structural changes. The objective of this study was to investigate trends in Pca prevalence and frequency of RP according to age structural change. MATERIALS AND METHODS We evaluated trends in Pca prevalence and RP rate using National Health Insurance Data from 2005 to 2015. Relationships for Pca prevalence and RP rate with age structural change were also determined. Primary outcomes included trends in Pca prevalence and RP rates according to age groups, comparing those before and after 2011. RESULTS Pca prevalence tended to increase before 2011 and decreased after 2011 in persons in the 60-years age group. RP rate increased pattern before 2011 and decreased after 2011 in age groups of 50s, 60s, and over 70s. Pca prevalence and age structural change showed a significantly positive relationship in all age groups, except for the age group under 40 years. RP rate and age structural change also showed a significantly positive relationship in all age groups. CONCLUSION Age structural change can affect the decreasing trend in Pca prevalence and RP rate in South Korea. Future studies are needed to validate this result.
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Affiliation(s)
- Hyun Young Lee
- Department of Urology, Soonchunhyang University Seoul Hospital, Soonchunhyang University Medical College, Seoul, Korea
| | - Suyeon Park
- Department of Biostatistics, Soonchunhyang University Seoul Hospital, Seoul, Korea
| | - Seung Whan Doo
- Department of Urology, Soonchunhyang University Seoul Hospital, Soonchunhyang University Medical College, Seoul, Korea
| | - Won Jae Yang
- Department of Urology, Soonchunhyang University Seoul Hospital, Soonchunhyang University Medical College, Seoul, Korea
| | - Yun Seob Song
- Department of Urology, Soonchunhyang University Seoul Hospital, Soonchunhyang University Medical College, Seoul, Korea
| | - Jae Heon Kim
- Department of Urology, Soonchunhyang University Seoul Hospital, Soonchunhyang University Medical College, Seoul, Korea.
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13
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Abstract
Male breast cancer (MBC) is a rare disease but, as a result of epidemiological collaborations, there is now greater clarity concerning endocrine risk factors. The significant rise in global age-standardised mean BMI in men is likely to lead to increases in incidence of maturity-onset diabetes and MBC. The metabolic changes accompanying obesity decrease androgens and sex hormone-binding globulin (SHBG), thereby increasing available oestrogens. The higher rates of MBC in North and Equatorial Africa are largely due to liver damage from endemic bilharziasis and hepatitis B causing elevated oestradiol (E2) levels from hepatic conversion of androgen. Klinefelter's syndrome (XXY) is associated with a 50-fold increase in incidence of MBC compared with XY males, and this is the most pronounced evidence for testicular malfunction amplifying risk. Delay in presentation means that up to 40% of cases have stage III or stage IV disease at diagnosis. No randomised controlled trials have been reported on endocrine treatment of advanced disease or adjuvant/neoadjuvant therapy following or preceding surgery. Tamoxifen is the most effective endocrine therapy, but side effects can lead to non-compliance in a substantial number of men. Aromatase inhibitors are less effective because they do not inhibit testicular oestrogen production. There is an urgent need for collaborative trials to provide an evidence base for the most effective endocrine and least toxic therapies for men with breast cancer.
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Chrysant SG, Chrysant GS. Cardiovascular benefits and risks of testosterone replacement therapy in older men with low testosterone. Hosp Pract (1995) 2018; 46:47-55. [PMID: 29478348 DOI: 10.1080/21548331.2018.1445405] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/08/2023]
Abstract
Many studies have shown that low testosterone (T) levels have been associated with increased risk for cardiovascular (CV) events, type 2 diabetes mellitus (T2DM), and strokes. In contrast, many other studies have demonstrated that normal T levels or the normalization of low T levels with testosterone replacement therapy (TRT) is associated with decreased incidence of CV events, T2DM, and strokes, besides improving sexual function and the quality of life. However, recent studies have indicated that TRT could lead to increased incidence of CV events and strokes. These latter studies have created a great controversy among physicians regarding these findings, who question the validity of their results. In order to get a better perspective on the current status of TRT in hypogonadal men, a focused Medline and EMBASE search of the English language literature was conducted between 2010 and 2017 using the terms hypogonadism, low Testosterone, cardiovascular disease, testosterone replacement therapy, benefits, risks, older men, mechanism of action, and 58 papers with pertinent information were selected and 48 papers were rejected. The selected papers will be discussed in this review. In conclusion, based on the current status of TRT, the majority of studies indicate that TRT is safe and is associated with prevention of CVD and strokes in hypogonadal men. However, the evidence is not uniform and the therefore, decision to administer TRT should be discussed with the patient till more definitive information becomes available.
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Affiliation(s)
- Steven G Chrysant
- a Department of Cardiology , University of Oklahoma Health Sciences Center , Oklahoma City , OK , USA
| | - George S Chrysant
- b Department of Cardiology , INTEGRIS Baptist Medical Center , Oklahoma City , OK , USA
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15
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Magnussen LV, Andersen PE, Diaz A, Ostojic J, Højlund K, Hougaard DM, Christensen AN, Nielsen TL, Andersen M. MR spectroscopy of hepatic fat and adiponectin and leptin levels during testosterone therapy in type 2 diabetes: a randomized, double-blinded, placebo-controlled trial. Eur J Endocrinol 2017; 177:157-168. [PMID: 28522646 DOI: 10.1530/eje-17-0071] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2017] [Revised: 04/30/2017] [Accepted: 05/18/2017] [Indexed: 01/06/2023]
Abstract
BACKGROUND Men with type 2 diabetes mellitus (T2D) often have lowered testosterone levels and an increased risk of cardiovascular disease (CVD). Ectopic fat increases the risk of CVD, whereas subcutaneous gluteofemoral fat protects against CVD and has a beneficial adipokine-secreting profile. HYPOTHESIS Testosterone replacement therapy (TRT) may reduce the content of ectopic fat and improve the adipokine profile in men with T2D. DESIGN AND METHODS A randomized, double-blinded, placebo-controlled study in 39 men aged 50-70 years with T2D and bioavailable testosterone levels <7.3 nmol/L. Patients were randomized to TRT (n = 20) or placebo gel (n = 19) for 24 weeks. Thigh subcutaneous fat area (TFA, %fat of total thigh volume), subcutaneous abdominal adipose tissue (SAT, % fat of total abdominal volume) and visceral adipose tissue (VAT, % fat of total abdominal volume) were measured by magnetic resonance (MR) imaging. Hepatic fat content was estimated by single-voxel MR spectroscopy. Adiponectin and leptin levels were measured by in-house immunofluorometric assay. Coefficients (b) represent the placebo-controlled mean effect of intervention. RESULTS TFA (b = -3.3 percentage points (pp), P = 0.009), SAT (b = -3.0 pp, P = 0.006), levels of adiponectin (b = -0.4 mg/L, P = 0.045), leptin (b = -4.3 µg/mL, P < 0.001), leptin:adiponectin ratio (b = -0.53, P = 0.001) and HDL cholesterol (b = -0.11 mmol/L, P = 0.009) decreased during TRT compared with placebo. Hepatic fat content and VAT were unchanged. CONCLUSIONS The effects of TRT on cardiovascular risk markers were ambiguous. We observed potentially harmful changes in cardiovascular risk parameters, markedly reduced subcutaneous fat and unchanged ectopic fat during TRT and a reduction in adiponectin levels. On the other hand, the decrease in leptin and leptin:adiponectin ratio assessments could reflect an amelioration of the cardiovascular risk profile linked to hyperleptinaemia in ageing men with T2D.
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Affiliation(s)
| | - P E Andersen
- Departments of Radiology, Odense University Hospital, Odense, Denmark
- Clinical Institute, University of Southern Denmark, Odense, Denmark
| | - A Diaz
- Departments of Radiology, Odense University Hospital, Odense, Denmark
| | - J Ostojic
- Centre of Radiology, Clinical Centre of Vojvodina, Faculty of Medicine-University of Novi Sad, Novi Sad, Serbia
| | - K Højlund
- Departments of Endocrinology and Metabolism
- Section of Molecular Diabetes & Metabolism, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark
| | - D M Hougaard
- Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark
| | - A N Christensen
- Department of Applied Mathematics and Computer Science, Technical University of Denmark, Lyngby, Denmark
| | | | - M Andersen
- Departments of Endocrinology and Metabolism
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16
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Cardioprotection by Low-dose of Estrogen and Testosterone at the Physiological Ratio on Ovariectomized Rats During Ischemia/Reperfusion Injury. J Cardiovasc Pharmacol 2017; 70:87-93. [DOI: 10.1097/fjc.0000000000000497] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
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17
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Ha JY, Shin TJ, Jung W, Kim BH, Park CH, Kim CI. Updated clinical results of active surveillance of very-low-risk prostate cancer in Korean men: 8 years of follow-up. Investig Clin Urol 2017; 58:164-170. [PMID: 28480341 PMCID: PMC5419108 DOI: 10.4111/icu.2017.58.3.164] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2016] [Accepted: 02/20/2017] [Indexed: 11/18/2022] Open
Abstract
Purpose Update and reanalysis of our experience of active surveillance (AS) for prostate cancer (PCa) in Korea. Materials and Methods A prospective, single-arm, cohort study was initiated in January 2008. Patients were selected according to the following criteria: Gleason sum ≤6 with single positive core with ≤30% core involvement, clinical stage≤T1c, prostate-specific antigen (PSA)≤10 ng/mL, and negative magnetic resonance imaging (MRI) results. Follow-up was by PSA measurement every 6 months, prostate biopsies at 1 year and then every 2–3 years, and MRI every year. Results A total of 80 patients were treated with AS. Median follow-up was 52 months (range, 6–96 months). Of them, 39 patients (48.8%) discontinued AS for various reasons (17, disease progression; 9, patient preference; 10, watchful waiting due to old age; 3, follow-up loss; 2, death). The probability of progression was 14.0% and 42.9% at 1 and 3 years, respectively. Overall survival was 97.5%. PCa-specific survival was 100%. Progression occurred in 5 of 7 patients (71.4%) with a prostate volume less than 30 mL, 7 of 40 patients (17.5%) with a prostate volume of 30 to 50 mL, and 5 of 33 patients (15.2%) with a prostate volume of 50 mL or larger. There were 8 detectable positive lesions on follow-up MRI. Of them, 6 patients (75%) had actual progressed disease. Conclusions Small prostate volume was associated with a tendency for cancer progression. MRI was helpful and promising for managing AS. Nevertheless, regular biopsies should be performed. AS is a safe and feasible treatment option for very-low-risk PCa in Korea. However, AS should continue to be used in carefully selected patients.
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Affiliation(s)
- Ji Yong Ha
- Department of Urology, Keimyung University School of Medicine, Daegu, Korea
| | - Teak Jun Shin
- Department of Urology, Keimyung University School of Medicine, Daegu, Korea
| | - Wonho Jung
- Department of Urology, Keimyung University School of Medicine, Daegu, Korea
| | - Byung Hoon Kim
- Department of Urology, Keimyung University School of Medicine, Daegu, Korea
| | - Choal Hee Park
- Department of Urology, Keimyung University School of Medicine, Daegu, Korea
| | - Chun Il Kim
- Department of Urology, Keimyung University School of Medicine, Daegu, Korea
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18
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Santok GDR, Abdel Raheem A, Kim LHC, Chang K, Lum TGH, Chung BH, Choi YD, Rha KH. Prostate-specific antigen 10-20 ng/mL: A predictor of degree of upgrading to ≥8 among patients with biopsy Gleason score 6. Investig Clin Urol 2017; 58:90-97. [PMID: 28261677 PMCID: PMC5330379 DOI: 10.4111/icu.2017.58.2.90] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2016] [Accepted: 12/22/2016] [Indexed: 11/18/2022] Open
Abstract
PURPOSE This study aimed to identify the predictors of upgrading and degree of upgrading among patients who have initial Gleason score (GS) 6 treated with robot-assisted radical prostatectomy (RARP). MATERIALS AND METHODS A retrospective review of the data of 359 men with an initial biopsy GS 6, localized prostate cancer who underwent RARP between July 2005 to June 2010 was performed. They were grouped into group 1 (nonupgrade) and group 2 (upgraded) based on their prostatectomy specimen GS. Logistic regression analysis of studied cases identified significant predictors of upgrading and the degree of upgrading after RARP. RESULTS The mean age and prostate-specific antigen (PSA) was 63±7.5 years, 8.9±8.77 ng/mL, respectively. Median follow-up was 59 months (interquartile range, 47-70 months). On multivariable analysis, age, PSA, PSA density and ≥2 cores positive were predictors of upgrading with (odds ratio [OR], 1.03; 95% confidence interval [CI], 1.01-1.06; p=0.003; OR, 1.006; 95% CI, 1.01-1.11; p=0.018; OR, 0.65; 95% CI, 0.43-0.98, p=0.04), respectively. On subanalysis, only PSA level of 10-20 ng/mL is associated with upgrading into GS ≥8. They also had lower biochemical recurrence free survival, cancer specific survival, and overall survival (p≤0.001, p=0.003, and p=0.01, respectively). CONCLUSIONS Gleason score 6 patients with PSA (10-20 ng/mL) have an increased risk of upgrading to pathologic GS (≥8), subsequently poorer oncological outcome thus require a stricter follow-up. These patients should be carefully counseled in making an optimal treatment decision.
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Affiliation(s)
- Glen Denmer R. Santok
- Department of Urology and Urological Science Institute, Yonsei University College of Medicine, Seoul, Korea
| | - Ali Abdel Raheem
- Department of Urology and Urological Science Institute, Yonsei University College of Medicine, Seoul, Korea
- Department of Urology, Tanta University Medical School, Tanta, Egypt
| | - Lawrence HC Kim
- Department of Urology and Urological Science Institute, Yonsei University College of Medicine, Seoul, Korea
| | - Kidon Chang
- Department of Urology and Urological Science Institute, Yonsei University College of Medicine, Seoul, Korea
| | - Trenton GH Lum
- Department of Urology and Urological Science Institute, Yonsei University College of Medicine, Seoul, Korea
| | - Byung Ha Chung
- Department of Urology and Urological Science Institute, Yonsei University College of Medicine, Seoul, Korea
| | - Young Deuk Choi
- Department of Urology and Urological Science Institute, Yonsei University College of Medicine, Seoul, Korea
| | - Koon Ho Rha
- Department of Urology and Urological Science Institute, Yonsei University College of Medicine, Seoul, Korea
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19
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Kloner RA, Carson C, Dobs A, Kopecky S, Mohler ER. Testosterone and Cardiovascular Disease. J Am Coll Cardiol 2016; 67:545-57. [PMID: 26846952 DOI: 10.1016/j.jacc.2015.12.005] [Citation(s) in RCA: 260] [Impact Index Per Article: 28.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2015] [Accepted: 12/01/2015] [Indexed: 10/22/2022]
Abstract
Testosterone (T) is the principal male sex hormone. As men age, T levels typically fall. Symptoms of low T include decreased libido, vasomotor instability, and decreased bone mineral density. Other symptoms may include depression, fatigue, erectile dysfunction, and reduced muscle strength/mass. Epidemiology studies show that low levels of T are associated with more atherosclerosis, coronary artery disease, and cardiovascular events. However, treating hypogonadism in the aging male has resulted in discrepant results in regard to its effect on cardiovascular events. Emerging studies suggest that T may have a future role in treating heart failure, angina, and myocardial ischemia. A large, prospective, long-term study of T replacement, with a primary endpoint of a composite of adverse cardiovascular events including myocardial infarction, stroke, and/or cardiovascular death, is needed. The Food and Drug Administration recently put additional restrictions on T replacement therapy labeling and called for additional studies to determine its cardiac safety.
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Affiliation(s)
- Robert A Kloner
- Huntington Medical Research Institutes, Pasadena, California; Division of Cardiovascular Medicine, Department of Medicine, Keck School of Medicine at University of Southern California, Los Angeles, California.
| | - Culley Carson
- Department of Urology, University of North Carolina, Chapel Hill, North Carolina
| | - Adrian Dobs
- Division of Endocrinology, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | | | - Emile R Mohler
- Section of Vascular Medicine, Division of Cardiovascular Disease, Perelman School of Medicine at the University of Pennsylvania, School of Medicine, Philadelphia, Pennsylvania
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20
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Sansone A, Sansone M, Lenzi A, Romanelli F. Testosterone Replacement Therapy: The Emperor's New Clothes. Rejuvenation Res 2016; 20:9-14. [PMID: 27124096 DOI: 10.1089/rej.2016.1818] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
The mean age of the world population has steadily increased in the last decades, as a result of increased life expectancy and reduced birth rate. Global aging has led to a greater worldwide cost for healthcare: hormonal alterations contribute to the pathogenesis of several conditions and might cause a significant reduction in the perceived sense of well-being. Menopause is archetypal of hormonal alterations occurring during aging: in males, sex hormones do not decrease abruptly, yet testosterone levels decrease steadily and continuously during aging, ultimately resulting in late-onset hypogonadism. Treatment of this condition might mitigate most symptoms; however, testosterone replacement therapy (TRT) should be prescribed only in selected patients and it should not be considered as an antiaging treatment. In recent years, different authors have questioned health risks associated with testosterone treatment; while position statements from many scientific societies seem to be reassuring, the Food and Drug Administration has issued a warning in regard to the possible side effects of this therapy. We aim to review recent controversies and discoveries in regard to TRT.
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Affiliation(s)
- Andrea Sansone
- Section of Medical Pathophysiology, Food Science and Endocrinology, Department of Experimental Medicine, Sapienza University of Rome , Rome, Italy
| | - Massimiliano Sansone
- Section of Medical Pathophysiology, Food Science and Endocrinology, Department of Experimental Medicine, Sapienza University of Rome , Rome, Italy
| | - Andrea Lenzi
- Section of Medical Pathophysiology, Food Science and Endocrinology, Department of Experimental Medicine, Sapienza University of Rome , Rome, Italy
| | - Francesco Romanelli
- Section of Medical Pathophysiology, Food Science and Endocrinology, Department of Experimental Medicine, Sapienza University of Rome , Rome, Italy
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21
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Xu M, Zhang L, Liang C. Is it appropriate to conduct conventional active surveillance for Asian men with low-risk prostate cancer? Int Urol Nephrol 2016; 48:1287-1289. [PMID: 27118567 DOI: 10.1007/s11255-016-1287-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2016] [Accepted: 04/07/2016] [Indexed: 01/06/2023]
Affiliation(s)
- Ming Xu
- Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Li Zhang
- Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, China. .,Institute of Urology, Anhui Medical University, Hefei, China.
| | - Chaozhao Liang
- Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, China. .,Institute of Urology, Anhui Medical University, Hefei, China.
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22
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Zhao R, Li Y, Dai W. Serum sex hormone and growth arrest-specific protein 6 levels in male patients with coronary heart disease. Asian J Androl 2016; 18:644-9. [PMID: 26924277 PMCID: PMC4955194 DOI: 10.4103/1008-682x.172825] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Epidemiological studies have shown a high prevalence of low serum testosterone levels in men with cardiovascular disease. Moreover, the tyrosine kinase receptor Axl, the ligand of which is growth arrest-specific protein 6 (GAS6), is expressed in the vasculature, and serum GAS6 levels are associated with endothelial dysfunction and cardiovascular events. Testosterone regulates GAS6 gene transcription directly, which inhibits calcification of vascular smooth muscle cells and provides a mechanistic insight into the cardioprotective action of androgens. This study was designed to determine the correlation between serum GAS6 and testosterone levels in male patients with coronary heart disease (CHD). We recruited 225 patients with CHD and 102 apparently healthy controls. Serum concentrations of GAS6 and soluble Axl were quantified by an enzyme-linked immunosorbent assay. Levels of high-sensitivity C-reactive protein, testosterone, estradiol, and other routine biochemical markers were also measured. Testosterone decreased from 432.69 ± 14.40 to 300.76 ± 6.23 ng dl-1 (P < 0.001) and GAS6 decreased from 16.20 ± 0.31 to 12.51 ± 0.19 ng ml-1 (P < 0.001) in patients with CHD, compared with control subjects. Multiple linear regression analysis showed that serum testosterone and GAS6 levels were positively associated in male patients with CHD. Alterations in GAS6 levels may influence the development of CHD. Downregulation of GAS6/Axl signaling in the presence of low sex hormone levels during disease progression is a potential mechanism by which GAS6 affects CHD. This study provides novel results regarding the influence of sex hormones on serum GAS6 levels in patients with CHD.
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Affiliation(s)
- Rui Zhao
- Department of Clinical Laboratory, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China
| | - Yan Li
- Department of Clinical Laboratory, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China,
Correspondence: Dr. Y Li ()
| | - Wen Dai
- Department of Clinical Laboratory, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China
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23
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Abstract
Testosterone has now become one of the most widely used medications throughout the world. The rapid growth of the testosterone market in the past 10 years is due to many factors. We currently have a worldwide aging population. In the US, the number of men 65 years old or older is increasing 2–3 times faster than the number of men younger than 65 years. In addition, poor general health and certain medical conditions such as diabetes/metabolic syndrome (MetS), cardiovascular disease (CVD), and osteoporosis have been associated with low serum testosterone levels.123 There are now fewer concerns regarding the development of prostate cancer (PCa) after testosterone therapy, making it a more attractive treatment option. Finally, the introduction of different forms of testosterone supplementation therapy (TST) with increased promotion, marketing, and direct-to-consumer advertising is also driving market growth. As the demand for TST continues to grow, it is becoming more important for clinicians to understand how to diagnose and treat patients with low testosterone.
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Affiliation(s)
- Mohit Khera
- Scott Department of Urology, Baylor College of Medicine, Houston, Texas, USA
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24
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Abstract
Non-alcoholic fatty liver disease (NAFLD) is a condition where there is excess accumulation of triglycerides in the liver in the absence of excess alcohol consumption. It ranges from simple steatosis to non-alcoholic steatohepatitis (NASH), which can progress to fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). NAFLD, one of the most common causes of chronic liver disease in Western populations, is the hepatic component of the metabolic syndrome (MetS) and is associated with increased visceral adipose tissue (VAT), insulin resistance, and dyslipidemia. Studies have also shown that testosterone deficiency is associated with increased VAT and insulin resistance in males while hyperandrogenemia has been associated with increased risk of insulin resistance and VAT in females. Thus, the aims of this review are to discuss the available experimental and epidemiological data evaluating the association between testosterone and NAFLD, to discuss the potential clinical relevance of these data, and to identify gaps in the literature.
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