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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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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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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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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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Rosiglitazone increases bioactive testosterone and reduces waist circumference in hypogonadal men with type 2 diabetes.
Kapoor, D, Channer, KS, Jones, TH
Diabetes & vascular disease research. 2008;(2):135-7
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The purpose of this study was to assess the effect of rosiglitazone on bioavailable, free and total testosterone levels in hypogonadal men with type 2 diabetes. Sixteen type 2 diabetic men with hypogonadism were studied before and after administration of rosiglitazone (8 mg/day) for six months, with assessments performed every two months on two consecutive days. We measured testosterone and sex hormone binding globulin (SHBG), visceral adiposity, high-sensitivity CRP (hs-CRP), lipids, microalbuminuria and blood pressure. There was a significant increase in free (p=0.01), bioavailable (p=0.007) and total testosterone (p=0.002), as well as SHBG (p=0.03) levels, with rosiglitazone treatment. Waist circumference and waist / hip ratio decreased with the improvement in insulin sensitivity and glycaemic control (p=0.01). There was also a significant reduction in hs-CRP (p=0.02) and urinary albumin excretion. No significant effect on blood pressure or the ratio of low-density lipoprotein cholesterol to high-density lipoprotein cholesterol (LDL to HDL) was seen. In conclusion, the insulin-sensitiser rosiglitazone increases bioavailable, free and total testosterone and SHBG levels in hypogonadal men with type 2 diabetes.
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Age and testosterone feedback jointly control the dose-dependent actions of gonadotropin-releasing hormone in healthy men.
Veldhuis, JD, Iranmanesh, A, Mulligan, T
The Journal of clinical endocrinology and metabolism. 2005;(1):302-9
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Healthy older men manifest combined declines in testosterone concentrations, LH secretory burst mass (amount of LH released per pulse), and feedback-sensitive regularity of unknown cause. To test a unifying hypothesis of simultaneous reductions in GnRH outflow, gonadotrope responsiveness to GnRH, and androgenic negative feedback, we monitored LH secretion 1) after bolus iv injection of a 1000-fold range of randomly ordered individual doses of GnRH on separate mornings, 2) during unmodified (eugonadal) or testosterone-withdrawn (hypoandrogenemic) negative feedback, and 3) in 16 young (age, 18-35 yr) and 15 older (age, 60-85 yr) healthy men. LH secretory burst mass and pattern regularity were quantitated by intensive blood sampling, high specificity LH beta-subunit-directed immunoradiometric assay, deconvolution analysis, and approximate entropy. GnRH dose responsiveness was assessed by four-parameter nonlinear regression analysis. We demonstrated that older men exhibit 1) delayed attainment of GnRH-evoked maximal LH secretion; 2) enhanced potency of GnRH stimulation in both the feedback-intact and feedback-withdrawn states; 3) elevated gonadotrope sensitivity to GnRH, unmasked by experimental testosterone depletion; 4) comparable young adult-like GnRH efficacy, independent of testosterone feedback milieu; and 5) diminished regularity of GnRH-induced LH release evident only during unmodified androgenic feedback. We conclude that a 3-fold interaction among GnRH dose, testosterone concentration, and age governs GnRH action, and age determines both testosterone-modulated and testosterone-independent actions of GnRH.
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Soy protein isolates of varying isoflavone content exert minor effects on serum reproductive hormones in healthy young men.
Dillingham, BL, McVeigh, BL, Lampe, JW, Duncan, AM
The Journal of nutrition. 2005;(3):584-91
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Inverse associations between soy and prostate cancer and the contribution of hormones to prostate cancer prompted the current study to determine whether soy protein could alter serum hormones in men. Thirty-five men consumed milk protein isolate (MPI), low-isoflavone soy protein isolate (SPI) (low-iso SPI; 1.64 +/- 0.19 mg isoflavones/d), and high-iso SPI (61.7 +/- 7.35 mg isoflavones/d) for 57 d each in a randomized crossover design. Twenty-four-hour urine samples indicated that urinary isoflavones were significantly increased by the high-iso SPI relative to the low-iso SPI and MPI. Serum collected on d 1, 29, and 57 of each treatment revealed that dihydrotestosterone (DHT) and DHT/testosterone were significantly decreased by the low-iso SPI [9.4% (P = 0.036) and 9.0% (P = 0.004), respectively] and the high-iso SPI [15% (P = 0.047) and 14% (P = 0.013), respectively], compared with the MPI at d 57. Other significant effects included a decrease in testosterone by the low-iso SPI relative to the MPI (P = 0.023) and high-iso SPI (P = 0.020) at d 29; an increase in dehydroepiandrosterone sulfate by the low-iso SPI relative to the MPI at d 29 (P = 0.001) and relative to the MPI (P = 0.0003) and high-iso SPI (P = 0.005) at d 57; and increases in estradiol and estrone by the low-iso SPI relative to the MPI at d 57 (P = 0.010 and P = 0.005, respectively). In conclusion, soy protein, regardless of isoflavone content, decreased DHT and DHT/testosterone with minor effects on other hormones, providing evidence for some effects of soy protein on hormones. The relevance of the magnitude of these effects to future prostate cancer risk requires further investigation.
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Testosterone administration to men increases hepatic lipase activity and decreases HDL and LDL size in 3 wk.
Herbst, KL, Amory, JK, Brunzell, JD, Chansky, HA, Bremner, WJ
American journal of physiology. Endocrinology and metabolism. 2003;(6):E1112-8
Abstract
Testosterone administration to men is known to decrease high-density lipoprotein cholesterol (HDL-C) and the subclasses HDL(2) and HDL(3). It also might increase the number of small, dense, low-density lipoprotein cholesterol (LDL-C) particles in hypogonadal men. The decrease in HDL-C and in LDL-C size is potentially mediated by hepatic lipase activity, which hydrolyzes lipoprotein phospholipids and triacylglycerol. To determine how HDL-C and LDL-C particles are affected by testosterone administration to eugonadal men, testosterone was administered as a supraphysiological dose (600 mg/wk) for 3 wk to elderly, obese, eugonadal men before elective hip or knee surgery, and lipids were measured by routine methods and by density gradient ultracentrifugation. Hepatic lipase activity increased >60% above baseline levels, and HDL-C, HDL(2), and HDL(3) significantly declined in 3 wk. In addition, the LDL-C peak particle density and the amount of LDL-C significantly increased. Testosterone is therefore a potent stimulator of hepatic lipase activity, decreasing HDL-C, HDL(2), and HDL(3) as well as increasing LDL particle density changes, all associated with increased cardiovascular risk.
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Pharmacokinetic properties of zolpidem in elderly and young adults: possible modulation by testosterone in men.
Olubodun, JO, Ochs, HR, von Moltke, LL, Roubenoff, R, Hesse, LM, Harmatz, JS, Shader, RI, Greenblatt, DJ
British journal of clinical pharmacology. 2003;(3):297-304
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AIMS: The influence of ageing on the pharmacokinetics of zolpidem, an extensively prescribed hypnotic medication, was evaluated in healthy human volunteers. METHODS A series of 16 elderly (age: 61-85 years) and 24 young (age: 22-42 years) volunteers received single 5 mg oral doses of zolpidem tartrate. Serum zolpidem concentrations were determined by HPLC with fluorescence detection in samples drawn during 8 h after dosage. The effect of testosterone on zolpidem biotransformation was evaluated in vitro using human liver microsomes. Possible induction of CYP3A protein expression and function was studied in cultured human hepatocytes. RESULTS Among men, apparent oral clearance of zolpidem was decreased in elderly compared to young subjects (3.8 vs 11.0 ml min-1 kg-1, P < 0.01), Cmax was increased (93 vs 40 ng ml-1, P < 0.01), and half-life increased (2.7 vs 1.5 h, P < 0.03). Among women, zolpidem oral clearance was decreased in the elderly (3.0 vs 5.8 ml min-1 kg-1, P < 0.02), Cmax increased (108 vs 60 ng ml-1, P < 0.001), with no difference in t1/2 (2.3 vs 2.4 h). Among male subjects, free serum testosterone concentrations were lower in the elderly (10.5 vs 19.0 pg ml-1, P < 0.01), and were significantly correlated with zolpidem clearance (r2 = 0.46, P < 0.001). Multiple regression analysis indicated a greater relative contribution of serum testosterone than age to the oral clearance of zolpidem among men. In human liver microsomes, co-incubation of zolpidem (10 micro m) with varying concentrations of testosterone produced activation of biotransformation of zolpidem to its principal hydroxylated metabolite. Maximum activation was achieved at equimolar concentrations of testosterone (10 micro m). However, testosterone did not induce immunoactive CYP3A4 expression or catalytic function in cultured human hepatocytes. CONCLUSIONS The increased Cmax and lower oral clearance of zolpidem in the elderly are consistent with recommendations of lower clinical doses of zolpidem in the elderly. Our clinical and in vitro data both suggest that reduced free serum testosterone may have a modulatory role in age-dependent changes in zolpidem pharmacokinetics in men.