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Guo W, Zhao S, Chang Q, Sun J, Fan Y, Liu J. Negative association between 15 obesity- and lipid-related indices and testosterone in adult males: a population based cross-sectional study. Lipids Health Dis 2025; 24:24. [PMID: 39863911 PMCID: PMC11762110 DOI: 10.1186/s12944-025-02436-6] [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: 09/23/2024] [Accepted: 01/11/2025] [Indexed: 01/27/2025] Open
Abstract
BACKGROUND An association exists between obesity and reduced testosterone levels in males. The propose of this research is to reveal the correlation between 15 indices linked to obesity and lipid levels with the concentration of serum testosterone, and incidence of testosterone deficiency (TD) among adult American men. METHODS The study utilized information gathered from the National Health and Nutrition Examination Survey (NHANES) carried out from 2011 to 2016. The condition known as TD is typically characterized by a total serum testosterone level that falls below 300 ng/dL. The analysis used weighted linear and logistic regression methods to announce the association between 15 obesity- and lipid-related factors and serum testosterone levels as well as TD. Subgroup analyses were further carried out to confirm and validate the findings. Additionally, restricted cubic spline plots were utilized to examine non-linear relationships. Receiver operating characteristic (ROC) curves were created for the 15 factors, and the area under the curves (AUC) was calculated to assess the efficacy of each factor in detecting TD. RESULTS Among a group of 3,540 adult males, it was observed that all 15 obesity- and lipid-related indices showed a negative relationship with testosterone concentration and a direct correlation with the presence of TD. After accounting for all covariates, the analysis revealed that individuals within the highest quartile (Q4) for metabolic score for visceral fat (METS-VF) had the excellent probability of developing TD (OR = 13.412, 95%CIs: 4.222, 42.262, P < 0.001). Additionally, a non-linear relationship was detected between the METS-VF with TD. Within the model that incorporated all adjustments, the triglyceride glucose-waist to height ratio (TyG-WHtR) has the best performance for predicting TD (Overall: AUC = 0.762, 95%CIs: 0.743, 0.782, cut-off = 5.186). CONCLUSION Elevated levels of these 15 markers were inversely related to testosterone levels and were indicative of an elevated risk of TD. Among all indices analyzed, TyG-WHtR demonstrated the highest predictive value. TRIAL REGISTRATION Not available.
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Affiliation(s)
- Wei Guo
- Department of Urology, Qilu Hospital of Shandong University, 107 Wenhuaxi Road Jinan, Shandong, 250012, People's Republic of China
| | - Shuo Zhao
- Department of Urology, Qilu Hospital of Shandong University, 107 Wenhuaxi Road Jinan, Shandong, 250012, People's Republic of China
| | - Qinzheng Chang
- Department of Urology, Qilu Hospital of Shandong University, 107 Wenhuaxi Road Jinan, Shandong, 250012, People's Republic of China
| | - Jiajia Sun
- Department of Urology, Qilu Hospital of Shandong University, 107 Wenhuaxi Road Jinan, Shandong, 250012, People's Republic of China
| | - Yidong Fan
- Department of Urology, Qilu Hospital of Shandong University, 107 Wenhuaxi Road Jinan, Shandong, 250012, People's Republic of China.
| | - Jikai Liu
- Department of Urology, Qilu Hospital of Shandong University, 107 Wenhuaxi Road Jinan, Shandong, 250012, People's Republic of China.
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Dalmiglio C, Bombardieri A, Mattii E, Sestini F, Fioravanti C, Castagna MG, Fiorini M, Dotta F, Cantara S. Analytical performance of free testosterone calculated by direct immunoluminometric method compared with the Vermeulen equation: results from a clinical series. Hormones (Athens) 2024; 23:313-319. [PMID: 38177558 DOI: 10.1007/s42000-023-00522-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2023] [Accepted: 12/20/2023] [Indexed: 01/06/2024]
Abstract
INTRODUCTION Testosterone (T) is a hormone that is crucial for primary and secondary sexual development in both males and females. Free testosterone (FT) represents the biologically active form of T, and its measurement is of great importance in clinical practice. While application of either equilibrium dialysis or ultrafiltration is considered to be the gold standard for FT assessment, these methods are expensive and not widely accessible. As an alternative, the Vermeulen formula is a commonly utilized calculated method. METHODS This clinical study, including 190 consecutive patients, was carried out to compare FT levels obtained through direct immunoluminometric assay and the Vermeulen formula. The comparison was performed using Passing-Bablok and Deming regression as well as the Bland-Altman plot. Sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were assessed. RESULTS The calculated method employing the Vermeulen formula was considered the gold standard. Passing-Bablok regression indicated a good agreement between the two methods, with slopes close to 1 for the whole series. Although the Bland-Altman plot demonstrated overall agreement, a potential proportional bias was observed in females. Deming regression confirmed excellent agreement and reliable estimates. Sensitivity and specificity analysis revealed that the direct method had a sensitivity of 75.0% and a specificity of 93.4% in all patients. However, sensitivity improved to 81.0% in males and dropped to 18.2% in females likely due to the low number of true positive cases. CONCLUSION The direct method exhibited comparable performance to the calculated method, but caution should be exercised when interpreting results, particularly in females. Further studies are necessary to validate its sensitivity and specificity in larger series.
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Affiliation(s)
- Cristina Dalmiglio
- Department of Medical, Surgical and Neurological Sciences, University of Siena, Viale Bracci 16, 53100, Siena, Italy
| | - Alessio Bombardieri
- Department of Medical, Surgical and Neurological Sciences, University of Siena, Viale Bracci 16, 53100, Siena, Italy
| | - Elisa Mattii
- Department of Medical, Surgical and Neurological Sciences, University of Siena, Viale Bracci 16, 53100, Siena, Italy
| | - Fausta Sestini
- Laboratory of Clinical and Translational Research, University Hospital of Siena, Siena, Italy
| | - Carla Fioravanti
- Laboratory of Clinical and Translational Research, University Hospital of Siena, Siena, Italy
| | - Maria Grazia Castagna
- Department of Medical, Surgical and Neurological Sciences, University of Siena, Viale Bracci 16, 53100, Siena, Italy
| | - Marcello Fiorini
- Laboratory of Clinical and Translational Research, University Hospital of Siena, Siena, Italy
| | - Francesco Dotta
- Department of Medical, Surgical and Neurological Sciences, University of Siena, Viale Bracci 16, 53100, Siena, Italy
| | - Silvia Cantara
- Department of Medical, Surgical and Neurological Sciences, University of Siena, Viale Bracci 16, 53100, Siena, Italy.
- Laboratory of Clinical and Translational Research, University Hospital of Siena, Siena, Italy.
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Shah SS, Kanani EAM, Kharat SK, Shah PS, Shah RM. Evaluation of the Incidence of Low Testosterone Levels in Young Male Adults with Moderate to Severe Obesity-Single-Centre Study from India. Obes Surg 2024; 34:836-840. [PMID: 38282174 DOI: 10.1007/s11695-024-07075-x] [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: 09/30/2023] [Revised: 01/20/2024] [Accepted: 01/22/2024] [Indexed: 01/30/2024]
Abstract
PURPOSE With the increase in obesity epidemic among Asians, it is necessary to evaluate the impact of obesity on this population. Low testosterone levels are known to be associated with obesity. This is the 1st study from Asia to evaluate incidence and magnitude of hypotestosteronemia in young adults with BMI more than 32.5 kg/m2 defined as moderate to severe obesity in Asians. MATERIALS AND METHODS One hundred thirty-four male patients with BMI more than 32.5 kg/m2, between 18 and 30 years old who visited a single bariatric facility between 2017 and 2020, were evaluated with BMI, total and free testosterone levels and clinical features of gynecomastia, hypogonadism, and thinning of pubic and armpit hair. Statistical analysis was performed using SPSS, Spearman's correlation coefficient, and ANOVA test. RESULTS 60.4% of patients (84/134) had low testosterone levels (< 300 ng/dl) and 23.9% (32/134) had levels between 300 and 400 ng/dl. 89.6% patients (120/134 had gynecomastia, 60.4% (81/134) had thinning of pubic and arm pit hair, and 62.7% (84/134) had hypogonadism. Testosterone levels showed a decreasing trend with increasing BMI, but it was not statistically significant. CONCLUSION Obesity is one of the important etiologies of hypotestosteronemia and its manifestations in young adults. The actual incidence may be significantly higher than what is reported in the literature. High-quality research is required to address questions of diagnosis and best treatment options.
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Affiliation(s)
- Shashank S Shah
- Laparo Obeso Centre (LOC Healthcare LLP), University of Bergen, Pune, India
| | | | | | - Poonam S Shah
- Laparo Obeso Centre (LOC Healthcare LLP), University of Bergen, Pune, India
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Chen X, Zhang Z, Niu H, Tian X, Tian H, Yao W, He H, Shi H, Li C, Luo J. Goat Milk Improves Glucose Metabolism in Type 2 Diabetic Mice and Protects Pancreatic β-Cell Functions. Mol Nutr Food Res 2024; 68:e2200842. [PMID: 37990402 DOI: 10.1002/mnfr.202200842] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Revised: 07/13/2023] [Indexed: 11/23/2023]
Abstract
SCOPE Consuming goat milk is known to benefit high-fat diet-fed and streptozocin (STZ)-induced diabetic rats, but the underlying mechanisms are unknown. This study is conducted to investigate the metabolic effects of a goat milk diet (a form of goat milk powder) on glucose homeostasis and pancreatic conditions in a mouse model of Type 2 diabetes mellitus (T2DM) induced by STZ. METHODS AND RESULTS T2DM mice are fed with a goat-milk-based diet containing 10.3% w/w goat milk powder for 10 weeks for investigating the in vivo effects; a β-cell line MIN6 cells are used to test the in vitro effects of digested goat milk (DGM). Goat milk diet improves the deleterious effects of STZ on fasting glucose levels and glucose tolerance, accelerates pancreatic structure recovery, and alters blood metabolites in mice. Based on the significant differences observed in metabolites, the key pathways, metabolite regulatory enzymes, metabolite molecular modules, and biochemical reactions are identified as critical integrated pathways. DGM promotes the cell activity, glucose transportation, and AKT activation in cultured STZ-treated MIN6 cells in vitro. CONCLUSIONS Goat milk diet improves glucose homeostasis and pancreatic conditions of T2DM mice, in association with improved blood metabolite profiles and activation of pancreatic AKT pathway.
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Affiliation(s)
- Xiaoying Chen
- Shaanxi Key Laboratory of Molecular Biology for Agriculture, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, China
| | - Zhifei Zhang
- Shaanxi Key Laboratory of Molecular Biology for Agriculture, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, China
| | - Huiming Niu
- Shaanxi Key Laboratory of Molecular Biology for Agriculture, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, China
| | - Xinmiao Tian
- Shaanxi Key Laboratory of Molecular Biology for Agriculture, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, China
| | - Huibin Tian
- Shaanxi Key Laboratory of Molecular Biology for Agriculture, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, China
| | - Weiwei Yao
- Shaanxi Key Laboratory of Molecular Biology for Agriculture, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, China
| | - Huanshan He
- Shaanxi Key Laboratory of Molecular Biology for Agriculture, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, China
| | - Huaiping Shi
- Shaanxi Key Laboratory of Molecular Biology for Agriculture, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, China
| | - Cong Li
- Shaanxi Key Laboratory of Molecular Biology for Agriculture, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, China
| | - Jun Luo
- Shaanxi Key Laboratory of Molecular Biology for Agriculture, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, China
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Espeland MA, Howard M, Bennett W, Robusto BA, Yasar S, Hugenschmidt CE, Luchsinger JA, Bahnson J, Yassine H, Johnson KC, Cook D, Hayden KM. Associations between cognitive function and endogenous levels of estradiol and testosterone in adults with type 2 diabetes. J Diabetes Complications 2022; 36:108268. [PMID: 35926332 PMCID: PMC10162709 DOI: 10.1016/j.jdiacomp.2022.108268] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2022] [Revised: 07/22/2022] [Accepted: 07/22/2022] [Indexed: 10/16/2022]
Abstract
AIMS To assess associations that endogenous estradiol and testosterone levels have with cognitive function in older adults with Type 2 diabetes mellitus (T2DM). METHODS We use data from the Look AHEAD clinical trial of behavioral weight loss. Endogenous estradiol and total testosterone levels were determined using stored serum from 996 individuals, mean age 69 years, at two times (averaging 4 years apart) during years 8-18 of follow-up. One to four standardized assessments of attention, executive function, memory, and verbal fluency were collected during this follow-up. Mixed effects models and multiple imputation were used to assess associations that estradiol and total testosterone levels had with body mass index and cognitive function. RESULTS Estradiol levels were not associated with cognitive function in either sex. Total testosterone levels were not associated with cognitive function in women, but greater total testosterone levels were associated with better verbal fluency in men (p < 0.001), most strongly among those carrying the APOE-e4 allele (interaction p = 0.02). The weight loss intervention left a legacy of relatively lower cognitive functioning among women, which was not mediated by current levels of sex hormones. CONCLUSIONS Behavioral weight loss intervention does not affect cognitive functioning through mechanisms related to estradiol or testosterone. CLINICALTRIALS gov Identifier: NCT00017953.
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Affiliation(s)
- Mark A Espeland
- Sticht Center for Healthy Aging and Alzheimer's Prevention, Wake Forest School of Medicine, Winston-Salem, NC, USA; Department of Biostatistics and Data Science, Wake Forest School of Medicine, Winston-Salem, NC, USA; Department of Social Sciences and Health Policy, Wake Forest School of Medicine, Winston-Salem, NC, USA.
| | - Marjorie Howard
- Department of Biostatistics and Data Science, Wake Forest School of Medicine, Winston-Salem, NC, USA.
| | - Wendy Bennett
- Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA.
| | - Brian A Robusto
- Sticht Center for Healthy Aging and Alzheimer's Prevention, Wake Forest School of Medicine, Winston-Salem, NC, USA.
| | - Sevil Yasar
- Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA.
| | - Christina E Hugenschmidt
- Sticht Center for Healthy Aging and Alzheimer's Prevention, Wake Forest School of Medicine, Winston-Salem, NC, USA.
| | - Jose A Luchsinger
- Department of Medicine, Columbia University Medical Center, New York, NY, USA.
| | - Judy Bahnson
- Sticht Center for Healthy Aging and Alzheimer's Prevention, Wake Forest School of Medicine, Winston-Salem, NC, USA.
| | - Hussein Yassine
- Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
| | - Karen C Johnson
- Department of Preventive Medicine, University of Tennessee Health Science Center, Memphis, TN, USA.
| | - Delilah Cook
- Department of Biostatistics and Data Science, Wake Forest School of Medicine, Winston-Salem, NC, USA
| | - Kathleen M Hayden
- Department of Social Sciences and Health Policy, Wake Forest School of Medicine, Winston-Salem, NC, USA.
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6
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Saleki K, Banazadeh M, Saghazadeh A, Rezaei N. Aging, testosterone, and neuroplasticity: friend or foe? Rev Neurosci 2022; 34:247-273. [PMID: 36017670 DOI: 10.1515/revneuro-2022-0033] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2022] [Accepted: 07/03/2022] [Indexed: 11/15/2022]
Abstract
Neuroplasticity or neural plasticity implicates the adaptive potential of the brain in response to extrinsic and intrinsic stimuli. The concept has been utilized in different contexts such as injury and neurological disease. Neuroplasticity mechanisms have been classified into neuroregenerative and function-restoring processes. In the context of injury, neuroplasticity has been defined in three post-injury epochs. Testosterone plays a key yet double-edged role in the regulation of several neuroplasticity alterations. Research has shown that testosterone levels are affected by numerous factors such as age, stress, surgical procedures on gonads, and pharmacological treatments. There is an ongoing debate for testosterone replacement therapy (TRT) in aging men; however, TRT is more useful in young individuals with testosterone deficit and more specific subgroups with cognitive dysfunction. Therefore, it is important to pay early attention to testosterone profile and precisely uncover its harms and benefits. In the present review, we discuss the influence of environmental factors, aging, and gender on testosterone-associated alterations in neuroplasticity, as well as the two-sided actions of testosterone in the nervous system. Finally, we provide practical insights for further study of pharmacological treatments for hormonal disorders focusing on restoring neuroplasticity.
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Affiliation(s)
- Kiarash Saleki
- Student Research Committee, Babol University of Medical Sciences, 47176 47745 Babol, Iran.,USERN Office, Babol University of Medical Sciences, 47176 47745 Babol, Iran.,Systematic Review and Meta-analysis Expert Group (SRMEG), Universal Scientific Education and Research Network (USERN), 14197 33151 Tehran, Iran
| | - Mohammad Banazadeh
- Systematic Review and Meta-analysis Expert Group (SRMEG), Universal Scientific Education and Research Network (USERN), 14197 33151 Tehran, Iran.,Pharmaceutical Sciences and Cosmetic Products Research Center, Kerman University of Medical Sciences, 76169 13555 Kerman, Iran
| | - Amene Saghazadeh
- Systematic Review and Meta-analysis Expert Group (SRMEG), Universal Scientific Education and Research Network (USERN), 14197 33151 Tehran, Iran.,Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, 14197 33151 Tehran, Iran
| | - Nima Rezaei
- Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, 14197 33151 Tehran, Iran.,Department of Immunology, School of Medicine, Tehran University of Medical Sciences, 14176 13151 Tehran, Iran.,Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), 14197 33151 Tehran, Iran
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7
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Кузнецов КО, Хайдарова РР, Хабибуллина РХ, Стыценко ЕС, Философова ВИ, Нуриахметова ИР, Хисамеева ЭМ, Важоров ГС, Хайбуллин ФР, Иванова ЕА, Горбатова КВ. [Testosterone and Alzheimer's disease]. PROBLEMY ENDOKRINOLOGII 2022; 68:97-107. [PMID: 36337024 PMCID: PMC9762454 DOI: 10.14341/probl13136] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 06/06/2022] [Accepted: 06/24/2022] [Indexed: 11/09/2022]
Abstract
Alzheimer's disease (AD) is a neurodegenerative disease that causes dementia in half of the cases. Asthma is usually found in people over 65 years of age. The etiopathogenesis of the disease is multifactorial and includes genetic factors, nutritional disorders, mitochondrial dysfunction, oxidative stress, and aging. Sex hormones have an important influence on the development of AD, as evidenced by a higher incidence in women than in men. Considering the significant influence of T on the maintenance of normal brain function, the present study is aimed at evaluating the impact of androgen deprivation therapy (ADT), as well as testosterone therapy, on the risk of AD development and progression. Although there is some clinical inconsistency between studies, androgens have a significant effect on brain function and are beneficial for AD patients. Low levels of circulating androgens should be considered as a significant risk factor for the development of AD and memory loss. With a reduced level of T in the plasma of men, its administration improves cognitive performance and memory, treatment should be started at an early stage of the disease. In men and women with AD, androgens improve mental state and slow the progression of the disease, providing a protective effect. In the future, it is necessary to conduct studies on a large population, taking into account personality factors and a more specific approach to assessing cognitive functions and the causal relationship of T administration in AD.
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Affiliation(s)
- К. О. Кузнецов
- Российский национальный исследовательский медицинский университет им. Н.И. Пирогова
| | | | - Р. Х. Хабибуллина
- Первый Санкт-Петербургский государственный медицинский университет им. акад. И.П. Павлова
| | - Е. С. Стыценко
- Санкт-Петербургский государственный педиатрический медицинский университет
| | - В. И. Философова
- Первый Санкт-Петербургский государственный медицинский университет им. акад. И.П. Павлова
| | | | | | - Г. С. Важоров
- Чувашский государственный университет им. И.Н. Ульянова
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8
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Bianchi VE. Impact of Testosterone on Alzheimer's Disease. World J Mens Health 2022; 40:243-256. [PMID: 35021306 PMCID: PMC8987133 DOI: 10.5534/wjmh.210175] [Citation(s) in RCA: 33] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2021] [Revised: 09/16/2021] [Accepted: 09/23/2021] [Indexed: 11/15/2022] Open
Abstract
Alzheimer’s disease (AD) is a neurodegenerative disease responsible for almost half of all dementia cases in the world and progressively increasing. The etiopathology includes heritability, genetic factors, aging, nutrition, but sex hormones play a relevant role. Animal models demonstrated that testosterone (T) exerted a neuroprotective effect reducing the production of amyloid-beta (Aβ), improving synaptic signaling, and counteracting neuronal death. This study aims to evaluate the impact of T deprivation and T administration in humans on the onset of dementia and AD. A search was conducted on MEDLINE and Scopus for the “androgen deprivation therapy” and “testosterone therapy” with “dementia” and “Alzheimer’s.” Studies lasting twenty years with low risk of bias, randomized clinical trial, and case-controlled studies were considered. Twelve articles on the effect of androgen deprivation therapy (ADT) and AD and seventeen on T therapy and AD were retrieved. Men with prostate cancer under ADT showed a higher incidence of dementia and AD. The effect of T administration in hypogonadal men with AD and cognitive impairment has evidenced some positive results. The majority of studies showed the T administration improved memory and cognition in AD while others did not find any benefit. Although some biases in the studies are evident, T therapy for AD patients may represent an essential clinical therapy to reduce dementia incidence and AD progression. However, more specific case-controlled trials on the effect of androgens therapy in men and women to reducing the onset of AD are necessary.
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Affiliation(s)
- Vittorio Emanuele Bianchi
- Department of Endocrinology and Metabolism, Clinical Research Center Stella Maris, Falciano, San Marino, Italy.
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9
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Mundell NL, Owen PJ, Dalla Via J, Macpherson H, Daly RM, Fraser SF. Does androgen deprivation impact associations between cognition and strength, fitness and function in community-dwelling men with prostate cancer? A cross-sectional study. BMJ Open 2021; 11:e058478. [PMID: 36415046 PMCID: PMC8719205 DOI: 10.1136/bmjopen-2021-058478] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
OBJECTIVES We investigated whether there were differences in associations between cognition with muscle strength, fitness and function in men with prostate cancer (PCa) treated with, and without androgen deprivation therapy (ADT) and non-PCa controls. A secondary aim was to compare differences in the prevalence of cognitive impairment. DESIGN This cross-sectional study compared 70 ADT-treated men with PCa aged 50-85 years to non-ADT-treated men (n=52) and non-PCa controls (n=70). SETTING University clinical exercise laboratory. INTERVENTIONS Nil. PRIMARY AND SECONDARY OUTCOME MEASURES Standardised assessments were conducted for cognition (learning, memory, attention, processing speed and executive function), muscle strength (grip strength and leg press), fitness (400 m walk), gait speed (4 m walk) and dual-tasking mobility (timed-up-and-go with a cognitive task). RESULTS ADT-treated men showed stronger associations between fitness and executive function and task switching relative to controls (both: p≤0.03). For both PCa groups (independent of ADT use), poorer dual-task mobility was more strongly associated with decreased psychomotor attention (both: p≤0.027) and global cognitive function (both: p≤0.031) compared with non-PCa controls. The overall prevalence of cognitive impairment was low (4%-13%) and did not differ between the groups. CONCLUSIONS The presence of PCa, with or without ADT treatment, did not increase the risk of cognitive impairment relative to non-PCa controls, yet did alter the associations between physical fitness and some measures of functional performance with certain cognitive domains. This highlights the importance of men with PCa maintaining fitness and functional capacity to optimise cognitive health. TRIAL REGISTRATION NUMBER This study was registered with the Australian and New Zealand Clinical Trials Registry (ACTRN12614000317695).
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Affiliation(s)
- Niamh L Mundell
- Institute for Physical Activity and Nutrition (IPAN), School of Exercise and Nutrition Sciences, Deakin University, Burwood, Victoria, Australia
| | - Patrick J Owen
- Institute for Physical Activity and Nutrition (IPAN), School of Exercise and Nutrition Sciences, Deakin University, Burwood, Victoria, Australia
| | - Jack Dalla Via
- Institute for Physical Activity and Nutrition (IPAN), School of Exercise and Nutrition Sciences, Deakin University, Burwood, Victoria, Australia
- Institute for Nutrition Research, School of Medical and Health Sciences, Edith Cowan University, Perth, Western Australia, Australia
| | - Helen Macpherson
- Institute for Physical Activity and Nutrition (IPAN), School of Exercise and Nutrition Sciences, Deakin University, Burwood, Victoria, Australia
| | - Robin M Daly
- Institute for Physical Activity and Nutrition (IPAN), School of Exercise and Nutrition Sciences, Deakin University, Burwood, Victoria, Australia
| | - Steve F Fraser
- Institute for Physical Activity and Nutrition (IPAN), School of Exercise and Nutrition Sciences, Deakin University, Burwood, Victoria, Australia
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10
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Popiołek A, Brzoszczyk B, Jarzemski P, Chyrek-Tomaszewska A, Wieczór R, Borkowska A, Bieliński M. Prostate-Specific Antigen and Testosterone Levels as Biochemical Indicators of Cognitive Function in Prostate Cancer Survivors and the Role of Diabetes. J Clin Med 2021; 10:jcm10225307. [PMID: 34830590 PMCID: PMC8619514 DOI: 10.3390/jcm10225307] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2021] [Revised: 11/10/2021] [Accepted: 11/12/2021] [Indexed: 11/16/2022] Open
Abstract
Prostate cancer (PC) is one of the most common malignancies in men. The increase in the number of PC survivors is associated with many problems including cognitive impairment. Early detection of such problems facilitates timely protective intervention. This study examined the association between prostate-specific antigen (PSA) or testosterone (T) levels and cognitive function in patients undergoing radical prostatectomy. Such a correlation could help identify patient groups at risk of cognitive impairment. Participants underwent clinical (demographic data, medical history, physical examination, and blood analyses) and neuropsychological assessment (cognitive test battery). Preoperative PSA or T levels were not associated with cognitive function. However, long-term follow-up after prostatectomy showed a strong correlation between PSA levels and the results of verbal memory and executive function tests. A trend toward significance was also observed for visuospatial memory. The levels of free T and total T were not correlated with cognitive function. Only the levels of free T after hormonal treatment were significantly correlated with executive functions. Comorbid diabetes affected these correlations. In conclusion, PSA levels at a distant postoperative time and free T level after hormonal treatment may be biomarkers of cognitive function.
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Affiliation(s)
- Alicja Popiołek
- Department of Clinical Neuropsychology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, 85-067 Bydgoszcz, Poland; (A.C.-T.); (A.B.); (M.B.)
- Department of Internal Diseases, Jan Biziel University Hospital No. 2 in Bydgoszcz, 85-163 Bydgoszcz, Poland;
- Correspondence: ; Tel.: +48-52-585-37-03
| | - Bartosz Brzoszczyk
- Department of Laparoscopic, General, and Oncological Urology, Jan Biziel University Hospital No. 2 in Bydgoszcz, 85-067 Bydgoszcz, Poland; (B.B.); (P.J.)
| | - Piotr Jarzemski
- Department of Laparoscopic, General, and Oncological Urology, Jan Biziel University Hospital No. 2 in Bydgoszcz, 85-067 Bydgoszcz, Poland; (B.B.); (P.J.)
| | - Aleksandra Chyrek-Tomaszewska
- Department of Clinical Neuropsychology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, 85-067 Bydgoszcz, Poland; (A.C.-T.); (A.B.); (M.B.)
- Department of Internal Diseases, Jan Biziel University Hospital No. 2 in Bydgoszcz, 85-163 Bydgoszcz, Poland;
| | - Radosław Wieczór
- Department of Internal Diseases, Jan Biziel University Hospital No. 2 in Bydgoszcz, 85-163 Bydgoszcz, Poland;
| | - Alina Borkowska
- Department of Clinical Neuropsychology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, 85-067 Bydgoszcz, Poland; (A.C.-T.); (A.B.); (M.B.)
| | - Maciej Bieliński
- Department of Clinical Neuropsychology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, 85-067 Bydgoszcz, Poland; (A.C.-T.); (A.B.); (M.B.)
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11
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Guan LY, Hou WL, Zhu ZH, Cao JQ, Tang Z, Yin XY, Xu DW, Yu X, Jia QF, Tang WJ, Zhang JP, Hui L. Associations among gonadal hormone, triglycerides and cognitive decline in female patients with major depressive disorders. J Psychiatr Res 2021; 143:580-586. [PMID: 33213891 DOI: 10.1016/j.jpsychires.2020.11.022] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2020] [Revised: 11/03/2020] [Accepted: 11/06/2020] [Indexed: 01/19/2023]
Abstract
BACKGROUND Cognitive impairment has been identified as a core feature of depression. Serum triglycerides (TG), gonadal hormone and sex difference were shown to influence cognitive performance. The purpose of this study was to investigate the associations among serum TG, gonadal hormone, sex difference and cognitive performance in patients with major depressive disorders (MDD). METHODS The enrolled 183 patients (male/female = 80/103) meeting DSM-IV criteria for MDD were divided into high TG group (patients-HTG) and normal TG group (patients-NTG) according to TG level. Serum TG, estradiol (E2) and testosterone (T) levels were measured by the glycerokinase peroxidase-peroxidase and chemiluminescence methods. Cognition was assessed by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The study was conducted between August 2016 and January 2020. RESULTS In female, patients-HTG had lower immediate memory, language, attention, delayed memory and RBANS total scores than patients-NTG after adjusting for covariates. There were significant differences in serum E2 and T levels between patients-HTG and patients-NTG in female after controlling for covariates. In female patients-HTG, serum E2 level was positively associated with immediate memory, delayed memory and RBANS total scores, and serum T level was positively related to immediate memory, language and RBANS total scores. These findings were not seen in male patients. CONCLUSIONS Our data suggested that patients-HTG exhibited poorer cognitive function compared with patients-NTG in female. Moreover, the decline in serum gonadal hormone level might contribute to the high TG development of female MDD, and was further implicated in their cognitive decline.
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Affiliation(s)
- Lu Yang Guan
- School of Mental Health, First School of Clinical Medicine, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, PR China; Research Center of Biological Psychiatry, The Affiliated Guangji Hospital of Soochow University, Soochow University, Suzhou, 215137, Jiangsu, PR China
| | - Wen Long Hou
- School of Mental Health, First School of Clinical Medicine, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, PR China; Research Center of Biological Psychiatry, The Affiliated Guangji Hospital of Soochow University, Soochow University, Suzhou, 215137, Jiangsu, PR China
| | - Zhen Hua Zhu
- Research Center of Biological Psychiatry, The Affiliated Guangji Hospital of Soochow University, Soochow University, Suzhou, 215137, Jiangsu, PR China
| | - Jia Qi Cao
- School of Mental Health, First School of Clinical Medicine, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, PR China; Research Center of Biological Psychiatry, The Affiliated Guangji Hospital of Soochow University, Soochow University, Suzhou, 215137, Jiangsu, PR China
| | - Zhen Tang
- Research Center of Biological Psychiatry, The Affiliated Guangji Hospital of Soochow University, Soochow University, Suzhou, 215137, Jiangsu, PR China
| | - Xu Yuan Yin
- Research Center of Biological Psychiatry, The Affiliated Guangji Hospital of Soochow University, Soochow University, Suzhou, 215137, Jiangsu, PR China
| | - Dong Wu Xu
- School of Mental Health, First School of Clinical Medicine, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, PR China
| | - Xin Yu
- School of Mental Health, First School of Clinical Medicine, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, PR China; Institute of Mental Health, Peking University, Beijing, 100083, PR China
| | - Qiu Fang Jia
- Research Center of Biological Psychiatry, The Affiliated Guangji Hospital of Soochow University, Soochow University, Suzhou, 215137, Jiangsu, PR China
| | - Wen Jie Tang
- School of Mental Health, First School of Clinical Medicine, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, PR China; Research Center of Biological Psychiatry, The Affiliated Guangji Hospital of Soochow University, Soochow University, Suzhou, 215137, Jiangsu, PR China.
| | - Jian-Ping Zhang
- Department of Psychiatry, Weill Cornell Medical College, Cornell University, New York, NY, 10605, USA
| | - Li Hui
- School of Mental Health, First School of Clinical Medicine, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, PR China; Research Center of Biological Psychiatry, The Affiliated Guangji Hospital of Soochow University, Soochow University, Suzhou, 215137, Jiangsu, PR China.
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12
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Zhan J, Ma X, Liu D, Liang Y, Li P, Cui J, Zhou Z, Wang P. Gut microbiome alterations induced by tributyltin exposure are associated with increased body weight, impaired glucose and insulin homeostasis and endocrine disruption in mice. ENVIRONMENTAL POLLUTION (BARKING, ESSEX : 1987) 2020; 266:115276. [PMID: 32835916 DOI: 10.1016/j.envpol.2020.115276] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/15/2020] [Revised: 06/15/2020] [Accepted: 07/19/2020] [Indexed: 06/11/2023]
Abstract
Tributyltin (TBT), an organotin compound once widely used in agriculture and industry, has been reported to induce obesity and endocrine disruption. Gut microbiota has a strong connection with the host's physiology. Nevertheless, the influences of TBT exposure on gut microbiota and whether TBT-influenced gut microbiota is related to TBT-induced toxicity remain unclear. To fill these gaps, ICR (CD-1) mice were respectively exposed to TBT at NOEL (L-TBT) and tenfold NOEL (H-TBT) daily by gavage for 8 weeks in the current study. The results showed that TBT exposure significantly increased body weight as well as epididymal fat, and led to adipocyte hypertrophy, dyslipidemia and impaired glucose and insulin homeostasis in mice. Additionally, TBT exposure significantly decreased the levels of T4, T3 and testosterone in serum. Also of note, TBT exposure changed gut microbiota composition mainly by decreasing Bacteroidetes and increasing Firmicutes proportions. To confirm the role of gut microbiota in TBT-induced overweight and hormonal disorders, fecal microbiota transplantation was performed and the mice receiving gut microbiota from H-TBT mice had similar phenotypes with their donor mice including significant body weight and epididymal fat gain, glucose and insulin dysbiosis and hormonal disorders. These results suggested that gut microbiome altered by TBT exposure was involved in the TBT-induced increased body weight, impaired glucose and insulin homeostasis and endocrine disruption in mice, providing significant evidence and a novel perspective for better understanding the mechanism by which TBT induces toxicity.
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Affiliation(s)
- Jing Zhan
- Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Science, China Agricultural University, No. 2, West Yuanmingyuan Road, Beijing, 100193, China
| | - Xiaoran Ma
- Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Science, China Agricultural University, No. 2, West Yuanmingyuan Road, Beijing, 100193, China
| | - Donghui Liu
- Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Science, China Agricultural University, No. 2, West Yuanmingyuan Road, Beijing, 100193, China
| | - Yiran Liang
- Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Science, China Agricultural University, No. 2, West Yuanmingyuan Road, Beijing, 100193, China
| | - Peize Li
- Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Science, China Agricultural University, No. 2, West Yuanmingyuan Road, Beijing, 100193, China
| | - Jingna Cui
- Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Science, China Agricultural University, No. 2, West Yuanmingyuan Road, Beijing, 100193, China
| | - Zhiqiang Zhou
- Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Science, China Agricultural University, No. 2, West Yuanmingyuan Road, Beijing, 100193, China
| | - Peng Wang
- Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Science, China Agricultural University, No. 2, West Yuanmingyuan Road, Beijing, 100193, China.
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13
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Cai Z, Li H. An Updated Review: Androgens and Cognitive Impairment in Older Men. Front Endocrinol (Lausanne) 2020; 11:586909. [PMID: 33281745 PMCID: PMC7691320 DOI: 10.3389/fendo.2020.586909] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2020] [Accepted: 10/12/2020] [Indexed: 12/16/2022] Open
Abstract
Androgens are some of the most important sex hormones in men, and they maintain important physiological activities in the human body. Cognitive impairment is one of the most common manifestations of aging in the elderly population and an important factor affecting the quality of life of elderly individuals. The levels of sex hormones in elderly people decrease with age, and low levels of androgens in older male individuals have been closely linked to the development of cognitive impairment. Basic studies have shown that androgens have neuroprotective effects and that androgen deficiency impairs cognitive function by increasing oxidative stress and decreasing synaptic plasticity, among other effects. Additionally, clinical studies have also shown that androgen deficiency is closely related to cognitive impairment. This article reviews the relationship between low androgen levels and cognitive impairment, their potential mechanisms, and the effects of testosterone supplementation in improving cognition.
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Affiliation(s)
- Zhonglin Cai
- Department of Urology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Hongjun Li
- Department of Urology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
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14
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Sripetchwandee J, Pintana H, Sa-Nguanmoo P, Boonnag C, Pratchayasakul W, Chattipakorn N, Chattipakorn SC. Comparative effects of sex hormone deprivation on the brain of insulin-resistant rats. J Endocrinol 2019; 241:JOE-18-0552.R2. [PMID: 30689543 DOI: 10.1530/joe-18-0552] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2018] [Accepted: 01/28/2019] [Indexed: 11/08/2022]
Abstract
Obese-insulin resistance following chronic high-fat diet consumption led to cognitive decline through several mechanisms. Moreover, sex hormone deprivation, including estrogen and testosterone, could be a causative factor in inducing cognitive decline. However, comparative studies on the effects of hormone-deprivation on the brain are still lacking. Adult Wistar rats from both genders were conducted sham operations or orchiectomies/ovariectomies and given a normal diet or high-fat diet for 4, 8, and 12 weeks. Blood was collected to determine the metabolic parameters. At the end of the experiments, rats were decapitated and their brains were collected to determine brain mitochondrial function, brain oxidative stress, hippocampal plasticity, insulin-induced long-term depression, dendritic spine density, and cognition. We found that male and female rats fed a high-fat diet developed obese-insulin resistance by week 8 and brain defects via elevated brain oxidative stress, brain mitochondrial dysfunction, impaired insulin-induced long-term depression, hippocampal dysplasticity, reduced dendritic spine density, and cognitive decline by week 12. In normal diet-fed rats, estrogen-deprivation, not testosterone-deprivation, induced obese-insulin resistance, oxidative stress, brain mitochondrial dysfunction, impaired insulin-induced long-term depression, hippocampal dysplasticity, and reduced dendritic spine density. In high-fat-diet-fed rats, estrogen deprivation, not testosterone-deprivation, accelerated and aggravated obese-insulin resistance and brain defects at week 8. In conclusion, estrogen deprivation aggravates brain dysfunction more than testosterone deprivation through increased oxidative stress, brain mitochondrial dysfunction, impaired insulin-induced long-term depression, and dendritic spine reduction. These findings may explain clinical reports which show more severe cognitive decline in aging females than males with obese-insulin resistance.
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Affiliation(s)
- Jirapas Sripetchwandee
- J Sripetchwandee, Neurophysiology unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai university, Chiang Mai, Thailand
| | - Hiranya Pintana
- H Pintana, Neurophysiology unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai university, Chiang Mai, Thailand
| | - Piangkwan Sa-Nguanmoo
- P Sa-nguanmoo, Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, United States
| | - Chiraphat Boonnag
- C Boonnag, Neurophysiology unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai university, Chiang Mai, Thailand
| | - Wasana Pratchayasakul
- W Pratchayasakul, Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Nipon Chattipakorn
- N Chattipakorn, Cardiac Electrophysiology Research and Training Center, Chiang Mai university, Chiang Mai, 50200, Thailand
| | - Siriporn C Chattipakorn
- S Chattipakorn, Department of Oral Biology and Diagnostic Sciences, Faculty of Dentistry, Chiang Mai University, Chiang Mai, 50200, Thailand
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15
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Kim N, Kim J, Yoo C, Lim K, Akimoto T, Park J. Effect of acute mid-intensity treadmill exercise on the androgen hormone level and uncoupling protein-1 expression in brown fat tissue of mouse. J Exerc Nutrition Biochem 2018; 22:15-21. [PMID: 29673241 PMCID: PMC5909077 DOI: 10.20463/jenb.2018.0003] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2018] [Accepted: 03/19/2018] [Indexed: 12/13/2022] Open
Abstract
[Purpose] Brown adipose tissue (BAT) plays an important role in metabolizing different substances, including androgens. The aim of this study was to determine whether a single bout of aerobic exercise would increase the androgen hormone concentration in mouse BAT and whether its increase was associated with uncoupling protein-1 (UCP-1), protein kinase A (PKA)-related mechanism in BAT. [Methods] Twenty, 9-week-old ICR adult male micewere randomly divided into three groups: Control (n=6, CON), Exercise (n=7, EX), and Exercise + SRD5A1A2 inhibitor (n=7, EXIN). SRD5A1A2 is an enzyme needed when free testosterone is metabolized to dihydrotestosterone (DHT). SRD5A1A2 was administered intraperitoneally in the EXIN group, while the CON and EX groups were treated with the vehicle only. One hour later, exercise was performed at 60–70% V˙O2max for 30minutes. The levels of testosterone and DHT in BAT were determined by ELISA, and UCP-1 mRNA level was examined by RT-PCR. UCP-1 and PKA protein levels were determined by western blotting. [Results] After a single period of exercise, testosterone and DHT concentrations in BAT were significantly higher in EX than those in CON, and lower in EXIN than those in EX. The ratio of phosphorylated PKA to total PKA in BAT was significantly higher in EX than that in CON, and lower in EXIN than that in EX. UCP-1 levels in BAT were not different in the three groups. [Conclusion] Aerobic exercise increased bioactive androgen hormone levels in BAT in association with the increase in phosphorylated PKA levels. In contrast, 30minutes of treadmill exercise did not affect UCP-1 expression.
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16
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Huffman J, Hoffmann C, Taylor GT. Integrating insulin-like growth factor 1 and sex hormones into neuroprotection: Implications for diabetes. World J Diabetes 2017; 8:45-55. [PMID: 28265342 PMCID: PMC5320748 DOI: 10.4239/wjd.v8.i2.45] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2016] [Revised: 09/24/2016] [Accepted: 11/22/2016] [Indexed: 02/05/2023] Open
Abstract
Brain integrity and cognitive aptitude are often impaired in patients with diabetes mellitus, presumably a result of the metabolic complications inherent to the disease. However, an increasing body of evidence has demonstrated the central role of insulin-like growth factor 1 (IGF1) and its relation to sex hormones in many neuroprotective processes. Both male and female patients with diabetes display abnormal IGF1 and sex-hormone levels but the comparison of these fluctuations is seldom a topic of interest. It is interesting to note that both IGF1 and sex hormones have the ability to regulate phosphoinositide 3-kinase-Akt and mitogen-activated protein kinases-extracellular signal-related kinase signaling cascades in animal and cell culture models of neuroprotection. Additionally, there is considerable evidence demonstrating the neuroprotective coupling of IGF1 and estrogen. Androgens have also been implicated in many neuroprotective processes that operate on similar signaling cascades as the estrogen-IGF1 relation. Yet, androgens have not been directly linked to the brain IGF1 system and neuroprotection. Despite the sex-specific variations in brain integrity and hormone levels observed in diabetic patients, the IGF1-sex hormone relation in neuroprotection has yet to be fully substantiated in experimental models of diabetes. Taken together, there is a clear need for the comprehensive analysis of sex differences on brain integrity of diabetic patients and the relationship between IGF1 and sex hormones that may influence brain-health outcomes. As such, this review will briefly outline the basic relation of diabetes and IGF1 and its role in neuroprotection. We will also consider the findings on sex hormones and diabetes as a basis for separately analyzing males and females to identify possible hormone-induced brain abnormalities. Finally, we will introduce the neuroprotective interplay of IGF1 and estrogen and how androgen-derived neuroprotection operates through similar signaling cascades. Future research on both neuroprotection and diabetes should include androgens into the interplay of IGF1 and sex hormones.
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17
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Pongkan W, Pintana H, Sivasinprasasn S, Jaiwongkam T, Chattipakorn SC, Chattipakorn N. Testosterone deprivation accelerates cardiac dysfunction in obese male rats. J Endocrinol 2016; 229:209-20. [PMID: 27000685 DOI: 10.1530/joe-16-0002] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2016] [Accepted: 03/17/2016] [Indexed: 12/20/2022]
Abstract
Low testosterone level is associated with increased risks of cardiovascular diseases. As obese-insulin-resistant condition could impair cardiac function and that the incidence of obesity is increased in aging men, a condition of testosterone deprivation could aggravate the cardiac dysfunction in obese-insulin-resistant subjects. However, the mechanism underlying this adverse effect is unclear. This study investigated the effects of obesity on metabolic parameters, heart rate variability (HRV), left ventricular (LV) function, and cardiac mitochondrial function in testosterone-deprived rats. Orchiectomized or sham-operated male Wistar rats (n=36per group) were randomly divided into groups and were given either a normal diet (ND, 19.77% of energy fat) or a high-fat diet (HFD, 57.60% of energy fat) for 12weeks. Metabolic parameters, HRV, LV function, and cardiac mitochondrial function were determined at 4, 8, and 12weeks after starting each feeding program. We found that insulin resistance was observed after 8weeks of the consumption of a HFD in both sham (HFS) and orchiectomized (HFO) rats. Neither the ND sham (NDS) group nor ND orchiectomized (NDO) rats developed insulin resistance. The development of depressed HRV, LV contractile dysfunction, and increased cardiac mitochondrial reactive oxygen species production was observed earlier in orchiectomized (NDO and HFO) rats at week 4, whereas HFS rats exhibited these impairments later at week 8. These findings suggest that testosterone deprivation accelerates the impairment of cardiac autonomic regulation and LV function via increased oxidative stress and impaired cardiac mitochondrial function in obese-orchiectomized male rats.
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Affiliation(s)
- Wanpitak Pongkan
- Cardiac Electrophysiology Research and Training CenterFaculty of Medicine, Chiang Mai University, Chiang Mai, Thailand Cardiac Electrophysiology UnitDepartment of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand Center of Excellence in Cardiac Electrophysiology ResearchChiang Mai University, Chiang Mai, Thailand
| | - Hiranya Pintana
- Cardiac Electrophysiology Research and Training CenterFaculty of Medicine, Chiang Mai University, Chiang Mai, Thailand Cardiac Electrophysiology UnitDepartment of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand Center of Excellence in Cardiac Electrophysiology ResearchChiang Mai University, Chiang Mai, Thailand
| | - Sivaporn Sivasinprasasn
- Cardiac Electrophysiology Research and Training CenterFaculty of Medicine, Chiang Mai University, Chiang Mai, Thailand Cardiac Electrophysiology UnitDepartment of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand Center of Excellence in Cardiac Electrophysiology ResearchChiang Mai University, Chiang Mai, Thailand
| | - Thidarat Jaiwongkam
- Cardiac Electrophysiology Research and Training CenterFaculty of Medicine, Chiang Mai University, Chiang Mai, Thailand Cardiac Electrophysiology UnitDepartment of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand Center of Excellence in Cardiac Electrophysiology ResearchChiang Mai University, Chiang Mai, Thailand
| | - Siriporn C Chattipakorn
- Cardiac Electrophysiology Research and Training CenterFaculty of Medicine, Chiang Mai University, Chiang Mai, Thailand Cardiac Electrophysiology UnitDepartment of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand Department of Oral Biology and Diagnostic ScienceFaculty of Dentistry, Chiang Mai University, Chiang Mai, Thailand
| | - Nipon Chattipakorn
- Cardiac Electrophysiology Research and Training CenterFaculty of Medicine, Chiang Mai University, Chiang Mai, Thailand Cardiac Electrophysiology UnitDepartment of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand Center of Excellence in Cardiac Electrophysiology ResearchChiang Mai University, Chiang Mai, Thailand
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18
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Abstract
Many cross-sectional analyses and longitudinal studies have examined the association between adiposity and pubertal development. In addition, the impact of an increased fat mass on reproduction and fertility in human obese men and in male animal models of obesity has been studied. A trend toward earlier pubertal development and maturation in both sexes has been shown, and the notion that obese boys might progress to puberty at a slower pace than their nonobese peers can no longer be substantiated. Impaired fertility markers and reduced reproductive functions have been observed in obesity. Obesity affects both pubertal development and fertility in men.
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Affiliation(s)
- Wieland Kiess
- Department of Women & Child Health, Hospital for Children and Adolescents, University of Leipzig, Liebigstr. 20a, Leipzig D 04103, Germany; Leipzig University Medical Centre, LIFE, Leipzig Civilization Diseases Research Centre, LIFE Child, Centre for Paediatric Research, Leipzig, Germany.
| | - Isabel V Wagner
- Department of Women & Child Health, Hospital for Children and Adolescents, University of Leipzig, Liebigstr. 20a, Leipzig D 04103, Germany; Leipzig University Medical Centre, LIFE, Leipzig Civilization Diseases Research Centre, LIFE Child, Centre for Paediatric Research, Leipzig, Germany; IFB Adiposity Diseases, University of Leipzig, Liebigstr. 20a, Leipzig D 04103, Germany
| | - Jürgen Kratzsch
- Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University of Leipzig, Paul-List-Street 13-15, Leipzig 04103, Germany
| | - Antje Körner
- Department of Women & Child Health, Hospital for Children and Adolescents, University of Leipzig, Liebigstr. 20a, Leipzig D 04103, Germany; Leipzig University Medical Centre, LIFE, Leipzig Civilization Diseases Research Centre, LIFE Child, Centre for Paediatric Research, Leipzig, Germany; IFB Adiposity Diseases, University of Leipzig, Liebigstr. 20a, Leipzig D 04103, Germany
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