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Androgens and hirsutism score of overweight women with polycystic ovary syndrome improved after vitamin D treatment: A randomized placebo controlled clinical trial.
Al-Bayyari, N, Al-Domi, H, Zayed, F, Hailat, R, Eaton, A
Clinical nutrition (Edinburgh, Scotland). 2021;(3):870-878
Abstract
BACKGROUND & AIM: The objective of this study was to investigate the effect of vitamin D treatment on androgen levels and hirsutism scores in overweight women with PCOS. METHODS A prospective, randomized, double-blind, placebo-controlled clinical study was conducted at King Abdullah University Hospital in Irbid, Jordan. Overweight Jordanian females aged 18-49 years with vitamin D deficiency and PCOS (n = 60) were assigned to two groups: the treatment group (n = 30) who received 50,000 IU per week of vitamin D3 and the control group (n = 30) who received a placebo. RESULTS After receiving the treatment for 12 consecutive weeks, the levels of total testosterone, parathyroid hormone, free androgen index, and hirsutism score were significantly decreased (P < 0.001), and the levels of 25-hydroxyvitamin D (25(OH)D), sex hormone binding globulin, and phosphorus were significantly increased (P < 0.05). Furthermore, significant changes were observed in ovarian volume and follicle numbers and size ultrasonography, and in the regularity of the menstrual cycle (P < 0.001). In the placebo group, no significant changes were observed in either androgen levels, hirsutism score, or menstrual regularity. CONCLUSION Vitamin D3 at a treatment dose of 50,000 IU per week improved 25(OH)D levels and decreased the hirsutism scores and androgen levels of overweight women with PCOS. These results could mean increased fertility and better reproductive health for overweight women with PCOS; the use of vitamin D3 as a treatment for these patients should be further investigated. CLINICALTRIALS. GOV REGESTRATION NUMBER NCT02328404.
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Comparison of metabolic effects of the progestational androgens dimethandrolone undecanoate and 11β-MNTDC in healthy men.
Yuen, F, Thirumalai, A, Fernando, FA, Swerdloff, RS, Liu, PY, Pak, Y, Hull, L, Bross, R, Blithe, DL, Long, JE, et al
Andrology. 2021;(5):1526-1539
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BACKGROUND Dimethandrolone (DMA) and 11β-methyl-19-nortestosterone (11β-MNT) are two novel compounds with both androgenic and progestational activity that are under investigation as potential male hormonal contraceptives. Their metabolic effects have never been compared in men. OBJECTIVE Assess for changes in insulin sensitivity and adiponectin and compare the metabolic effects of these two novel androgens. MATERIALS/METHODS In two clinical trials of DMA undecanoate (DMAU) and 11β-MNT dodecylcarbonate (11β-MNTDC), oral prodrugs of DMA and 11β-MNT, healthy men received drug, or placebo for 28 days. Insulin and adiponectin assays were performed on stored samples. Mixed model analyses were performed to compare the effects of the two drugs. Student's t test, or the non-parametric Kruskal-Wallis test as appropriate, was used to evaluate for an effect of active drug versus placebo. RESULTS Class effects were seen, with decrease in HDL-C and SHBG, and increase in weight and hematocrit, with no statistically significant differences between the two compounds. No changes in fasting glucose, fasting insulin, or HOMA-IR were seen with either compound. There was a slight decrease in adiponectin with DMAU that was not seen with 11β-MNTDC. An increase in LDL-C was seen with 11β-MNTDC but not with DMAU. DISCUSSION There were no significant changes in insulin resistance after 28 days of oral administration of these novel androgens despite a mild increase in weight. There may be subtle differences in their metabolic impacts that should be explored in future studies. CONCLUSION Changes in metabolic parameters should be carefully monitored when investigating androgenic compounds.
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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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Androgens and Overall Survival in Patients With Metastatic Castration-resistant Prostate Cancer Treated With Docetaxel.
Ryan, CJ, Dutta, S, Kelly, WK, Middleberg, R, Russell, C, Morris, MJ, Taplin, ME, Halabi, S, ,
Clinical genitourinary cancer. 2020;(3):222-229.e2
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BACKGROUND Pre-treatment androgen levels are associated with overall survival (OS) in patients with metastatic castration-resistant prostate cancer (CRPC) treated with androgen synthesis inhibitors. The current study sought to determine whether pre-treatment serum androgens predict clinical outcome among patients with metastatic CRPC treated with docetaxel chemotherapy. MATERIALS AND METHODS Data were obtained from 1050 men who were chemotherapy-naive prior to treatment with docetaxel, prednisone, and either bevacizumab or placebo (CALGB 90401). Pretreatment serum assays for testosterone, androstenedione, and dehydroepiandrosterone (DHEA) were performed with tandem liquid chromatography-mass spectrometry. RESULTS Median values for testosterone, androstenedione, and DHEA were 1.00, 13.50, and 8.12 ng/dL, respectively. The median was used to define the midpoint between low and high values. In univariate analysis, median OS for low versus high levels was 21.4 and 24.2 months for testosterone, 23.8 and 21.9 months for androstenedione, and 20.2 and 25.2 months for DHEA (P = NS). In multivariable analysis of all androgens, baseline DHEA was prognostic of ≥ 50% PSA decline from baseline (P = .008). In multivariable analysis adjusting for 10 known prognostic values and prior ketoconazole use for metastatic CRPC, a 10-unit increase in baseline testosterone increased risk of death (hazard ratio, 1.11; 95% confidence interval, 1.01-1.23; P = .039), whereas a 10-unit increase in androstenedione lowered risk of death (hazard ratio, 0.92; 95% confidence interval, 0.88-0.97; P = .001). CONCLUSION Consistent with prior studies, higher androstenedione levels in patients with metastatic CRPC treated with docetaxel are associated with improved survival. However pretreatment levels of other androgen levels are associated with varied effects on clinical outcome in chemotherapy-treated patients.
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Differential effects of testosterone on circulating neutrophils, monocytes, and platelets in men: Findings from two trials.
Gagliano-Jucá, T, Pencina, KM, Guo, W, Li, Z, Huang, G, Basaria, S, Bhasin, S
Andrology. 2020;(5):1324-1331
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BACKGROUND Testosterone treatment increases erythrocytes in men, but its effects on leukocyte and platelet counts are unknown and could affect its safety. OBJECTIVE To determine whether testosterone affects circulating leukocytes and platelets in men. METHODS Secondary analyses of two randomized testosterone trials were performed: the 5α-reductase (5aR) and OPTIMEN trials. In 5aR trial, 102 healthy men, 21-50 years (mean age 38), received a long-acting GnRH agonist, and 50, 125, 300, or 600 mg/week testosterone enanthate (TE) plus placebo or 2.5 mg/ day dutasteride for 20 weeks. In OPTIMEN, 78 functionally limited men, ≥65 years (mean age 72) with protein intake ≤ 0.83 g kg-1 day-1 , were randomized to controlled diets with 0.8 g kg-1 day-1 protein or 1.3 g kg-1 day-1 protein plus placebo or TE (100 mg/week) for 6 months. Changes from baseline in total and differential leukocyte count, and platelet count were evaluated. RESULTS In 5aR, testosterone administration was associated with increases in total leukocyte (estimated change from baseline 40, 490, 1230, and 1280 cells/µL, P < .001), neutrophil (65.1, 436.1, 1177.2, and 1192.2 cells/µL, P < .001), monocyte (-20.2, 24.5, 90.6, and 143.9 cells/µL, P < .001), platelet (-7.3, 8.4, 8.7, and 8.9 × 103 cells/µL, P = .033), and erythrocyte counts. Testosterone did not affect absolute lymphocyte count. Similar increase in total leukocyte count was observed with testosterone treatment in OPTIMEN (change 0.77 × 103 cells/µL, P vs placebo = 0.004). CONCLUSIONS Testosterone administration in men differentially increases neutrophil and monocyte counts. These findings, together with its erythropoietic effects, suggest that testosterone promotes the differentiation of hematopoietic progenitors into the myeloid lineage. These findings have potential mechanistic, therapeutic, and safety implications.
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Effects of vitamin D supplementation on androgens in men with low testosterone levels: a randomized controlled trial.
Lerchbaum, E, Trummer, C, Theiler-Schwetz, V, Kollmann, M, Wölfler, M, Heijboer, AC, Pilz, S, Obermayer-Pietsch, B
European journal of nutrition. 2019;(8):3135-3146
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PURPOSE It has been hypothesized that vitamin D is associated with androgen levels in men. We, therefore, aimed to evaluate whether vitamin D supplementation increases serum total testosterone (TT) levels in men with low TT levels at baseline. METHODS The Graz Vitamin D&TT-RCT is a single-center, double-blind, randomized placebo-controlled trial conducted between March 2013 and November 2017 at the endocrine outpatient clinic at the Medical University of Graz, Austria. One-hundred healthy men with serum TT levels < 10.4 nmol/l and 25-hydroxyvitamin D [25(OH)D] levels < 75 nmol/l participated in the trial. Subjects were randomized to receive 20,000 IU of vitamin D3/week (n = 50) or placebo (n = 50) for 12 weeks. Primary outcome was TT measured using mass spectrometry. Secondary outcomes were free testosterone, free androgen index, sex hormone-binding globulin, estradiol, follicle-stimulating hormone, luteinizing hormone, metabolic characteristics, and body composition. RESULTS Ninety-four men [mean age and 25(OH)D: 47 (± 12) years and 56.3 (± 18.3) nmol/l, respectively] completed the study. We found no significant treatment effect on serum TT or on the remaining secondary outcome variables. CONCLUSION Vitamin D treatment had no effect on serum TT levels in middle-aged healthy men with low TT levels.
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The effect of resistant dextrin as a prebiotic on metabolic parameters and androgen level in women with polycystic ovarian syndrome: a randomized, triple-blind, controlled, clinical trial.
Gholizadeh Shamasbi, S, Dehgan, P, Mohammad-Alizadeh Charandabi, S, Aliasgarzadeh, A, Mirghafourvand, M
European journal of nutrition. 2019;(2):629-640
Abstract
INTRODUCTION Polycystic ovary syndrome (PCOS) is one of the most common abnormalities in women of reproductive age that can lead to a variety of metabolic and reproductive disorders. Studies reveal that a healthy diet is the most effective way for treating the risk factors associated with metabolic disorders and place greater emphasis on the consumption of prebiotic foods. The present study aims to determine the effect of resistant Dextrin on metabolic parameters, including lipid profile, fasting blood glucose (FBS) and high sensitivity C-reactive protein (hsCRP), and androgen levels, including serum levels of dehydroepiandrosterone sulfate (DHEA-S) and free testosterone, as the primary outcomes, and manifestations of PCOS including menstrual cycle irregularity and hirsutism, as the secondary outcomes. METHODS This randomized, controlled, triple-blind, clinical trial was conducted on 62 women aged 18-45 in Tabriz, Iran, in 2016-2017. The participants were divided into a prebiotic group and a placebo group using block randomization. The prebiotic group consumed 20 g of resistant dextrin dissolved in a glass of water and the placebo group 20 g of maltodextrin also dissolved in a glass of water on a daily basis for 3 months. To measure the serum lipid profile, FBS, hsCRP, DHEA-S and free testosterone before and 3 months after the intervention, 5-ml blood samples were collected from the participants and analyzed using the ELISA method. The Ferriman-Gallwey scale for assessing hirsutism and a checklist for assessing menstrual cycle characteristics were completed before and 3 months after the intervention. A general linear model was used to analyze the data. RESULTS No statistically significant differences were observed between the two groups in terms of sociodemographic characteristics and baseline values. 3 months after the intervention, based on the ANCOVA and after adjusting for the baseline values, the mean serum levels of LDL-C (adjusted mean difference = - 29.79; 95% CI = - 43.37 to - 16.21; P < 0.001), triglyceride (AMD = - 38.50; 95% CI = - 59.73 to - 17.28; P = 0.001), total cholesterol (AMD = - 29.98; 95% CI = - 40.14 to - 19.82; P < 0.001), FBS (AMD = - 11.24; 95% CI = - 15.43 to - 7.06; P < 0.001), hsCRP (AMD = - 1.75; 95% CI = - 2.92 to - 0.57; P = 0.004), DHEA-S (AMD = - 0.7; 95% CI = - 1.34 to - 0.13; P = 0.017) and free testosterone (AMD = - 0.32; 95% CI = - 0.56 to - 0.08; P = 0.010) revealed a statistically significant decrease in the intervention group compared to the placebo group, while the mean serum HDL-C showed a statistically significant increase in this group compared to the placebo group (AMD = 5.82; 95% CI = 2.27-9.37; P = 0.002). 3 months after the intervention, there was a significant difference between the two groups in terms of menstrual cycle intervals and hirsutism (P < 0.001). CONCLUSION Resistant dextrin consumption can regulate metabolic parameters and androgen levels and manifestations including hirsutism and menstrual cycle irregularity in women with PCOS.
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The impact of testosterone replacement therapy on glycemic control, vascular function, and components of the metabolic syndrome in obese hypogonadal men with type 2 diabetes.
Groti, K, Žuran, I, Antonič, B, Foršnarič, L, Pfeifer, M
The aging male : the official journal of the International Society for the Study of the Aging Male. 2018;(3):158-169
Abstract
OBJECTIVE This study set out to assess effects of testosterone replacement therapy (TRT) on parameters of metabolic syndrome and vascular function in obese hypogonadal males with type 2 diabetes mellitus (DM2). STUDY DESIGN Fifty-five obese hypogonadal diabetic males on oral hypoglycemic treatment were enrolled into this one-year, double-blind, randomized, placebo-controlled clinical study. Group T (n = 28) was treated with testosterone undecanoate (1000 mg i.m. every 10 weeks) while group P (n = 27) received placebo. METHODS Anthropometrical and vascular measurements - flow-mediated dilatation (FMD) and intima media thickness (IMT) - biochemical and hormonal blood sample analyses were performed at the start of the study and after one year. Derived parameters (BMI, HOMA-IR, calculated free testosterone (cFT) and bioavailable testosterone (BT)) were calculated. RESULTS TRT resulted in reduction of HOMA-IR by 4.64 ± 4.25 (p < .001), HbA1c by 0.94 ± 0.88% points (p < .001), and an increase in FMD by 2.40 ± 4.16% points (p = .005). CONCLUSION TRT normalized serum testosterone levels, improved glycemic control and endothelial function while exerting no ill effects on the study population.
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The effect of vitamin D supplementation in combination with low-calorie diet on anthropometric indices and androgen hormones in women with polycystic ovary syndrome: a double-blind, randomized, placebo-controlled trial.
Jafari-Sfidvajani, S, Ahangari, R, Hozoori, M, Mozaffari-Khosravi, H, Fallahzadeh, H, Nadjarzadeh, A
Journal of endocrinological investigation. 2018;(5):597-607
Abstract
PURPOSE Polycystic ovary syndrome (PCOS) is known as the most common endocrine disorder in reproductive age women. The aim of this studywas to evaluate the effects of vitamin D supplementation in combination with low-calorie diet on anthropometric indices, reproductive hormones and menstrual regularity in overweight and obese PCOS women. METHODS In this randomized controlled clinical trial, 60 PCOS women with vitamin D insufficiency were randomly assigned to 12 weeks of either (1) weight-loss intervention + 50,000 IU/week oral vitamin D3 or (2) weight-loss intervention + placebo. At the beginning and end of the study, the anthropometric indices, body composition, 25-hydroxyvitamin D, total testosterone, dehydroepiandrosterone sulfate (DHEAS), sex hormone-binding globulin (SHBG) and free androgen index (FAI) were measured and regularity of menses was compared among the two groups. RESULT After 12-week intervention, median of serum 25-hydroxyvitamin D3 significantly increased from 18.5 (10.75-20) ng/ml to 42.69 (34-53.25) ng/ml in vitamin D group compared to placebo group (p < 001). Moreover, there was a significant improvement in frequency regular menstrual cycle (p = 0.01). Mean of weight, body mass index, fat mass, waist and hip circumference and waist-to-hip ratio significantly decreased in both groups, but was not different between two groups. Mean of total testosterone insignificantly decreased from 0.7 to 0.5 ng/ml in vitamin D group (p = 0.18). In addition, we did not observe significant differences regarding DHEAS, FAI and SHBG between two groups. CONCLUSIONS In women with PCOS, androgen profile did not change with vitamin D supplementation when combined with low-calorie diet, but menstrual frequency significantly improved. CLINICAL TRIAL REGISTRATION NUMBER IRCT2016062710826N19.
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Effects of Dietary Approach to Stop Hypertension diet on androgens, antioxidant status and body composition in overweight and obese women with polycystic ovary syndrome: a randomised controlled trial.
Azadi-Yazdi, M, Karimi-Zarchi, M, Salehi-Abargouei, A, Fallahzadeh, H, Nadjarzadeh, A
Journal of human nutrition and dietetics : the official journal of the British Dietetic Association. 2017;(3):275-283
Abstract
BACKGROUND Polycystic ovary syndrome (PCOS) is the most common endocrine disease in reproductive age women. The present study aimed to determine the effects of Dietary Approaches to Stop Hypertension (DASH) diet on reproductive hormones, plasma total antioxidant status and anthropometric indices in overweight and obese PCOS women. METHODS In this randomised controlled clinical trial, 60 women with PCOS were randomly assigned to one of two diets with energy restriction: the DASH diet and a control diet. The DASH and control diets consisted of 50-55% carbohydrate, 15-20% protein and 25-30% total fat. The DASH diet was designed to be rich in vegetables, fruits, whole grains and low-fat dairy products, as well as low in saturated fats, cholesterol, refined grains and sweets. In the present study, the anthropometric indices, body composition, total testosterone, androstenedione, sex hormone binding globulin (SHBG), free androgen index and 2,2'-diphenyl-1-picryylhydrazyl (DPPH) scavenging activity were measured before and after 3 months. RESULTS The consumption of DASH diet compared to the control diet was associated with a significant reduction in weight [-5.78 (1.91) kg versus -4.34 (2.87) kg, P = 0.032], body mass index (BMI) [-2.29 (0.15) kg m-2 versus -1.69 (0.20) kg m-2 , P = 0.02], fat mass [-3.23(1.66) kg versus -2.13 (1.26) kg, P = 0.008] and serum androstenedione [-1.75 (1.39) ng mL-1 versus -1.02 (0.72) ng mL-1 , P-value = 0.019]. Increased concentrations of SHBG [28.80 (21.71) versus 11.66(18.82) nmol L-1 , P = 0.003) and DPPH scavenging activity [30.23% (19.09) versus 12.97% (25.12) were also found in the DASH group. CONCLUSIONS The DASH diet could improve weight loss, BMI and fat mass. Furthermore, it could result in a significant reduction in serum androstenedione and a significant increase in antioxidant status and SHBG.