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1.
Serum Vitamin D Affected Type 2 Diabetes though Altering Lipid Profile and Modified the Effects of Testosterone on Diabetes Status.
Wang, L, Liu, X, Hou, J, Wei, D, Liu, P, Fan, K, Zhang, L, Nie, L, Li, X, Huo, W, et al
Nutrients. 2020;(1)
Abstract
Numerous studies have investigated the associations between serum vitamin D or testosterone and diabetes; however, inconsistencies are observed. Whether there is an interaction between vitamin D and testosterone and whether the lipid profile (total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C)) mediates the association between vitamin D and diabetes is unclear. To investigate the effect of vitamin D and testosterone on impaired fasting glucose (IFG) or type 2 diabetes mellitus (T2DM), 2659 participants from the Henan Rural Cohort were included in the case-control study. Generalized linear models were utilized to estimate associations of vitamin D with IFG or T2DM and interactive effects of vitamin D and testosterone on IFG or T2DM. Principal component analysis (PCA) and mediation analysis were used to estimate whether the lipid profile mediated the association of vitamin D with IFG or T2DM. Serum 25(OH)D3, 25(OH)D2, and total 25(OH)D levels were negatively correlated with IFG (odds ratios (ORs) (95% confidence intervals (CIs)): 0.99 (0.97, 1.00), 0.85 (0.82, 0.88), and 0.97 (0.96, 0.98), respectively). Similarity results for associations between serum 25(OH)D2 and total 25(OH)D with T2DM (ORs (95%CIs): 0.84 (0.81, 0.88) and 0.97 (0.96, 0.99)) were observed, whereas serum 25(OH)D3 was negatively correlated to T2DM only in the quartile 2 (Q2) and Q3 groups (both p < 0.05). The lipid profile, mainly TC and TG, partly mediated the relationship between 25(OH)D2 or total 25(OH)D and IFG or T2DM and the proportion explained was from 2.74 to 17.46%. Furthermore, interactive effects of serum 25(OH)D2, total 25(OH)D, and testosterone on T2DM were observed in females (both p for interactive <0.05), implying that the positive association between serum testosterone and T2DM was vanished when 25(OH)D2 was higher than 10.04 ng/mL or total 25(OH)D was higher than 40.04 ng/mL. Therefore, ensuring adequate vitamin D levels could reduce the prevalence of IFG and T2DM, especially in females with high levels of testosterone.
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Testosterone Administration During Energy Deficit Suppresses Hepcidin and Increases Iron Availability for Erythropoiesis.
Hennigar, SR, Berryman, CE, Harris, MN, Karl, JP, Lieberman, HR, McClung, JP, Rood, JC, Pasiakos, SM
The Journal of clinical endocrinology and metabolism. 2020;(4)
Abstract
CONTEXT Severe energy deprivation markedly inhibits erythropoiesis by restricting iron availability for hemoglobin synthesis. OBJECTIVE The objective of this study was to determine whether testosterone supplementation during energy deficit increased indicators of iron turnover and attenuated the decline in erythropoiesis compared to placebo. DESIGN This was a 3-phase, randomized, double-blind, placebo-controlled trial. SETTING The study was conducted at the Pennington Biomedical Research Center. PATIENTS OR OTHER PARTICIPANTS Fifty healthy young males. INTERVENTION(S): Phase 1 was a 14-day free-living eucaloric controlled-feeding phase; phase 2 was a 28-day inpatient phase where participants were randomized to 200 mg testosterone enanthate/week or an isovolumetric placebo/week during an energy deficit of 55% of total daily energy expenditure; phase 3 was a 14-day free-living, ad libitum recovery period. MAIN OUTCOME MEASURE(S): Indices of erythropoiesis, iron status, and hepcidin and erythroferrone were determined. RESULTS Hepcidin declined by 41%, indicators of iron turnover increased, and functional iron stores were reduced with testosterone administration during energy deficit compared to placebo. Testosterone administration during energy deficit increased circulating concentrations of erythropoietin and maintained erythropoiesis, as indicated by an attenuation in the decline in hemoglobin and hematocrit with placebo. Erythroferrone did not differ between groups, suggesting that the reduction in hepcidin with testosterone occurs through an erythroferrone-independent mechanism. CONCLUSION These findings indicate that testosterone suppresses hepcidin, through either direct or indirect mechanisms, to increase iron turnover and maintain erythropoiesis during severe energy deficit. This trial was registered at www.clinicaltrials.gov as #NCT02734238.
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3.
The Effect of Macronutrients on Reproductive Hormones in Overweight and Obese Men: A Pilot Study.
Pearce, KL, Tremellen, K
Nutrients. 2019;(12)
Abstract
Hypogonadal obese men find it difficult to lose weight. We investigated whether the modification of macronutrient intake can alter testosterone levels independently of the body mass index. Fasted overweight or obese fertile men were asked to consume meals of polyunsaturated fats (PUFA), monounsaturated fats (MUFA), refined carbohydrates (CHO, orange juice, OJ), whey and egg albumin and mixed meals of PUFA and CHO, PUFA and egg albumin, and CHO and egg albumin. Blood was collected at fasting, then hourly for 5 h and analysed to determine the levels of testosterone and other hormones. We found PUFA and MUFA or a mixed meal of PUFA and CHO significantly reduced serum testosterone production to a similar degree over a 5 h period. PUFA decreased serum testosterone levels by 3.2 nmol/L after 1 h compared to baseline (p = 0.023), with this suppression remaining significant up to 5 h postprandially (2.1 nmol/L; p = 0.012). The net overall testosterone levels were reduced by approximately 10 nmol/L × h by PUFA, MUFA and PUFA combined with CHO. CHO alone had little effect on testosterone levels, whereas egg albumin was able to increase them (7.4 cf 2.0 nmol/L × h). Therefore, for men wishing to optimize their testosterone levels, it may be wise to avoid a high fat intake, drink liquids such as water or OJ or even consider fasting. ANZCTR, Australia; ACTRN12617001034325.
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Obesity and Insulin Resistance, Not Polycystic Ovary Syndrome, Are Independent Predictors of Bone Mineral Density in Adolescents and Young Women.
Pereira-Eshraghi, CF, Chiuzan, C, Zhang, Y, Tao, RH, McCann, M, Neugut, YD, Printz, A, Fennoy, I, Cree-Green, M, Oberfield, SE, et al
Hormone research in paediatrics. 2019;(6):365-371
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Abstract
INTRODUCTION Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders that affects females of reproductive age. The characteristic features of PCOS individually have opposing effects on bone mineral density (BMD); however, their cumulative effect on BMD has not been clearly defined. Adolescence and young adulthood span a crucial period in achieving peak bone mass. Thus, a better understanding of the impact of PCOS on BMD in this age group is needed. OBJECTIVES To determine whether BMD is different between young females with PCOS and controls and to identify factors that influence BMD in this population. METHODS Data from four cross-sectional studies with a total of 170 females aged 12-25 years with PCOS (n = 123) and controls (n = 47) with a wide range of BMIs (18.7-53.4 kg/m2) were analyzed. Participants had fasting glucose, insulin, and free and total testosterone concentrations measured. HOMA-IR was calculated. Whole-body BMD was assessed by dual-energy X-ray absorptiometry. Multiple regression analysis for predicting BMD included PCOS status, menstrual age, obesity, HOMA-IR, and free testosterone. RESULTS HOMA-IR and total and free testosterone were significantly higher in PCOS compared to controls but there was no difference in BMD z-score between PCOS (0.8 ± 1.0) and controls (0.6 ± 1.0) (p = 0.36). Obesity (p = 0.03) and HOMA-IR (p = 0.02) were associated with BMD z-score. CONCLUSIONS Obesity status and insulin resistance, but not PCOS status, were each independently associated with BMD in adolescents and young women who spanned a wide range of BMIs.
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Associations of IGF-1 and Adrenal Androgens with Cognition in Childhood.
Mäntyselkä, A, Haapala, EA, Lindi, V, Häkkinen, MR, Auriola, S, Jääskeläinen, J, Lakka, TA
Hormone research in paediatrics. 2019;(5):329-335
Abstract
BACKGROUND Little is known about the association between adrenarche and cognition in general populations of children. We therefore studied the associations of dehydroepiandrosterone sulfate (DHEAS), androstenedione (A4), testosterone, insulin-like growth factor-1 (IGF-1), and adrenarche with cognition among prepubertal children. METHODS These cross-sectional analyses are based on baseline data of the Physical Activity and Nutrition in Children Study. A total of 387 children (183 girls, 204 boys) were included in the analyses. Raven's Coloured Progressive Matrices (CPM) score was used to assess nonverbal reasoning. Serum adrenal androgens and IGF-1 concentrations were measured and clinical signs of androgen action were evaluated. RESULTS Higher IGF-1 among boys (β = 0.149, p =0.033) was related to a better Raven's CPM score after adjustment for age and parental education. Adrenal androgens in girls or boys or IGF-1 in girls were not associated with the score. There were no differences in Raven's CPM score between children with biochemical adrenarche (DHEAS ≥1.08 µmol/L; ≥40 µg/dL) or with clinical signs of androgen action and children without them. CONCLUSION The results suggest that higher serum IGF-1 among boys is related to better cognition in prepubertal children. We could not provide evidence for the associations of adrenal maturation with cognition in prepubertal children.
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Vigorous Physical Activity is Associated with Regular Aerobic Exercise-Induced Increased Serum Testosterone Levels in Overweight/Obese Men.
Kumagai, H, Yoshikawa, T, Zempo-Miyaki, A, Myoenzono, K, Tsujimoto, T, Tanaka, K, Maeda, S
Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme. 2018;(1):73-79
Abstract
Testosterone is a male sex hormone and low circulating testosterone levels are associated with various health disorders in men. Obesity results in reduced circulating testosterone levels in men. Previously, we demonstrated that lifestyle modifications (combination of aerobic exercise and dietary modification) increase circulating testosterone levels in overweight/obese men. However, the effect of regular aerobic exercise on serum testosterone levels remains unclear. The purpose of this study was to investigate the effect of a 12-week aerobic exercise intervention on circulating testosterone levels in normal-weight and overweight/obese men. Sixteen normal-weight men and twenty-eight overweight/obese men completed a 12-week aerobic exercise intervention. Before and after the intervention, we measured serum total testosterone, free testosterone, and bioavailable testosterone levels, and categorized the physical activity levels (light, moderate, or vigorous) in all participants. At baseline, serum total testosterone, free testosterone, and bioavailable testosterone levels were significantly lower in overweight/obese men than in normal-weight men (all p<0.01). After the 12-week aerobic exercise intervention, serum total testosterone, free testosterone, and bioavailable testosterone levels significantly increased in overweight/obese men (p<0.01). In addition, stepwise multivariable linear regression analysis revealed the increase in vigorous physical activity was independently associated with increased serum total testosterone levels (β=0.47, p=0.011). We demonstrated that a 12-week aerobic exercise intervention increased serum total testosterone, free testosterone, and bioavailable testosterone levels in overweight/obese men. We suggest that an increase in vigorous physical activity increased circulating testosterone levels in overweight/obese men.
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Efficacy of FurosapTM, a novel Trigonella foenum-graecum seed extract, in Enhancing Testosterone Level and Improving Sperm Profile in Male Volunteers.
Maheshwari, A, Verma, N, Swaroop, A, Bagchi, M, Preuss, HG, Tiwari, K, Bagchi, D
International journal of medical sciences. 2017;(1):58-66
Abstract
Background: Dietary fiber rich fenugreek (Trigonella foenum-graecum) seeds have exhibited cardioprotective, hypolipidemic and other health benefits. Furosap (FS), an innovative, patented, 20% protodioscin-enriched extract was developed in our laboratory from fenugreek seeds. This study examined the free and total testosterone levels, sperm profile and morphology, sexual health, mood and mental alertness, and broad spectrum safety parameters of FS in 50 male volunteers following supplementation over a period of 12 weeks. Methods: Institutional Review Board (IRB) and other regulatory approvals were obtained for our study. This one-arm, open-labelled, multi-center study was conducted in 50 male volunteers (age: 35 to 65 years) over a period of 12 weeks to determine the efficacy of FS (500 mg/day/subject) on free and total testosterone levels, sperm profile, sperm morphology, libido and sexual health, mood and mental alertness, and broad spectrum safety parameters. Results: Free testosterone levels were improved up to 46% in 90% of the study population. 85.4% of the study population showed improvements in sperm counts. Sperm morphology improved in 14.6% of volunteers. Majority of the subjects enrolled in the study demonstrated improvements in mental alertness and mood. Furthermore, cardiovascular health and libido were significantly improved. Extensive safety parameters were evaluated which included blood chemistry data. No significant changes were observed in serum lipid function, cholesterol, triglyceride, HDL and LDL levels, hemogram (CBC), hepatotoxicity and nephrotoxicity. Conclusion: Overall, the results demonstrate that FS, enriched in 20% protodioscin, is safe and effective in attenuating testosterone levels, healthy sperm profile, mental alertness, cardiovascular health and overall performance in human subjects.
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Clomiphene citrate effect in obese men with low serum testosterone treated with metformin due to dysmetabolic disorders: A randomized, double-blind, placebo-controlled study.
Pelusi, C, Giagulli, VA, Baccini, M, Fanelli, F, Mezzullo, M, Fazzini, A, Bianchi, N, Carbone, MD, De Pergola, G, Mastroroberto, M, et al
PloS one. 2017;(9):e0183369
Abstract
CONTEXT Low testosterone (T) levels are often found in obese men with impaired glucose tolerance (IGT) and overt type 2 diabetes (T2DM); however, the mechanisms underlying this condition and its correct therapy are still under debate. OBJECTIVE To evaluate the effectiveness of clomiphene citrate (CC) in increasing endogenous T levels in obese men with low serum T and with IGT or T2DM treated with metformin (MET). DESIGN Cross-over, randomized, double-blind, placebo-controlled study. METHODS 24 obese men, aged 47.3 ±. 6.3 (range 35-55 years), with low T level (≤3 ng/mL) and naïve diagnosis of IGT or T2DM were included. Subjects were randomized to CC 25 mg/day or placebo (Plac) with MET 2 g/day for 3 months. After a 6-week wash-out period, subjects were moved to the alternative arm for additional 3 months. Clinical evaluation and blood exams performed prior to and at the end of treatment. RESULTS Of 24 randomized, 21 were evaluable, classified as IGT (n = 11) or T2DM (n = 10). Compared to baseline levels, T levels increased significantly after 3 months of CC treatment (3.03±0.80 to 5.99±1.67 ng/mL P<0.001) but not after the Plac treatment (2.87±0.78 to 3.09±0.84 ng/mL P<0.001 between the treatments). T changes were similar in IGT and T2DM subjects. Gonadotropins as well raised significantly after CC treatment (LH 3.83±1.45 to 8.53±6.40 mU/mL; FSH 4.84±1.67 to 10.15±5.08 mU/mL P<0.001 respectively), whereas no changes for LH (3.51±1.59 to 3.63±1.39 mU/mL) but a smooth increased for FSH (4.61±2.49 to 5.39±2.65 mU/mL; P = 0.004) were shown after Plac treatment (LH P = 0.001 and FSH P = 0.002 between treatments). Furthermore, fasting glucose (106.8±23.2 to 101.1±25.7 mg/dL; P = 0.004), insulin (19.3±12.1 to 15.6±10.1 μU/mL; P = 0.010) and HOMA-IR (4.94±2.89 to 3.69±2.12; P = 0.001) decreased significantly during the CC treatment period, whereas no significant changes were observed in any of these parameters in the Plac treatment. CONCLUSIONS A low dose of CC therapy was able to significantly increase serum T levels in all participants with mild modifications of clinical and metabolic parameters. TRIAL REGISTRATION EudraCT 2011-000439-10.
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Lipid Accumulation Product (LAP) as an Index of Metabolic and Hormonal Disorders in Aging Men.
Rotter, I, Rył, A, Szylińska, A, Pawlukowska, W, Lubkowska, A, Laszczyńska, M
Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association. 2017;(3):176-182
Abstract
Lipid accumulation product (LAP) is an index used for evaluating lipid overaccumulation in adults. Our study aimed at assessing associations between LAP and metabolic syndrome (MetS) and its components, age-related testosterone deficiency syndrome (TDS), low-density cholesterol (LDL), as well as HOMA-IR (insulin resistance ratio), insulin level in non-diabetics and total testosterone (TT), estradiol E2, dehydroepiandrosterone sulphate (DHEAs) and sex hormone-binding globulin (SHBG) in aging men.313 men aged 50-75 were surveyed with regard to the prevalence of diabetes (T2DM) and hypertension (HT). Anthropometric measurements, including waist circumference and arterial pressure, were performed. We also determined the levels of fasting plasma glucose (FPG), total cholesterol (TC), high-density cholesterol (HDL), low-density cholesterol (LDL), triglyceride (TG), insulin, TT, SHBG, DHEAs, and E2.Patients with diagnosed MetS, T2DM, HT, obesity, overweight and TDS had a significantly higher LAP compared to those without these conditions. LAP was significantly positively correlated with serum TC, FPG, insulin, DHEAs, as well as APB-systolic concentration, and negatively correlated with HDL, TT, and SHBG.LAP may then be used as a simple and inexpensive biomarker of metabolic disorders, and in risk assessment related to testosterone deficiency in aging men.
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Does Fluoride Affect Serum Testosterone and Androgen Binding Protein with Age-Specificity? A Population-Based Cross-Sectional Study in Chinese Male Farmers.
Duan, L, Zhu, J, Wang, K, Zhou, G, Yang, Y, Cui, L, Huang, H, Cheng, X, Ba, Y
Biological trace element research. 2016;(2):294-299
Abstract
Many studies have demonstrated that exposure to excess fluoride was associated with a variety of diseases. Little is known about the variation of testosterone (T) levels caused by fluoride exposure. The aim of this study is to explore the association of fluoride exposure and age with serum T and androgen-binding protein (ABP) levels in male farmers. A cross-sectional study was conducted in a county of Henan Province, China, including high fluoride exposure from drinking water villages and control villages. Male farmers aged 18-55 years old who lived in these villages were recruited by cluster sampling and divided into a higher fluoride exposure group (HFG) and a lower fluoride exposure group (LFG) according to the level of urinary fluoride. Levels of T and ABP in serum were measured using chemiluminescence immunoassay (CLIA) and enzyme-linked immunosorbent assay (ELISA) respectively. Markedly lower T levels were observed in male farmers from the HFG than in those from the LFG (t = 2.496, P < 0.05). Furthermore, younger farmers, 18-29 and 30-39 years old, may be the most likely to have lower T levels when exposed to fluoride (P < 0.05). No significant differences were observed in serum ABP levels in all male farmers between the two groups with different fluoride exposure. These results supported that excess fluoride exposure decreased serum T levels of male farmers with age-specificity.