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Nathan Goodyear

Clinical and serologic markers of stage and prognosis in small cell lung cancer. A mult... - 0 views

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    TK-1 useful in evaluation of disease stage and therapy efficacy. TK-1 was used in conduction with LDH, CEA, NSE, and TPA.
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Ergonomic Wheelchair - 0 views

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    Ergonomic wheelchair series provides users with a large selection of ultra lightweight wheelchairs that can help improve life. This series has features that include a high strength lightweight frame, foldable and easy to store, breathable anti-bacterial, anti-staining, removable and machine washable cushion. Also includes the exclusive S-Shape Seating System, which provides increased stability, better weight distribution and lowers the risk of pressure sores and spinal injury. The patented S-Shape Seating System that comes with every wheelchair model in this series provides an ergonomic seating frame that conforms and flexes to the shape of body. Karma S Ergo 115 Wheelchair: This model features our S-Shape Seating System and is our number one best seller for many reasons. At a mere 11.3 kg in weight with detachable foot rest and many features such as removable machine washable and dry-able cushions treated by AEIGIS treated anti-microbial coated seating system. Karma S-Ergo 115 Wheelchair Features: Ergonomic Handrims & S-Shape Ergonomic Seating System Fixed armrest w/ wider concave armpads Swing In & Away Footrests Backrest Pouch attached to the upholstery 24" flat free polyurethane tires, high tread, flat free wheels Seat width: 16"x17" or 18"x17" or 20"x 17" Silver 1/4" Aegis Anti-Bacterial Upholstery, washable Folding backrest / folding seat for easy traveling "Tube-in Center" foot-plate, assures better side leg support High strength, starting weight at only 11.3 kg. (w/o footrests) 7×1" Polyurethane front casters Upholstery: Black breathable mesh bottom & top AEIGIS Frame Color: Pearl Silver or Rose Red Weight Capacity of 115 kg. Karma S-Ergo 115 Wheelchair Measurements: Seat Width 16 inch., 18 inch., 20 inch. Seat Depth 17 inch. Armrest Height 8 inch. Seat Height 19 inch. Back Height 17 inch. Overall Height 36 inch. Overall Open Width 23 inch., 25 inch., 27 inch. Folded Width 12 inch. Overall Length 39 i
Nathan Goodyear

Hypercalcemia of malignancy and new treatment options - 0 views

  • Hypercalcemia of malignancy occurs as the result of direct bone metastasis and via humoral mechanisms such as parathyroid hormone-related protein (PTHrP) or 1,25-dihydroxyvitamin D mediated pathways
  • ectopic secretion of parathyroid hormone (PTH) has been implicated
  • Hypercalcemia due to osteolytic bone lesions is common in multiple myeloma, leukemia, and breast cancer
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  • Humoral hypercalcemia is predominant in squamous cell, renal cell and ovarian cancers, and lymphomas are associated with 1,25-dihydroxyvitamin D mediated hypercalcemia
  • 20% of cases of hypercalcemia of malignancy and is frequently encountered in multiple myeloma, metastatic breast cancer, and to a lesser extent in leukemia and lymphoma
  • Physiologic bone turnover requires the complementary activity of osteoblasts – mesenchymal stem cell-derived bone-forming cells – and bone-resorbing cells of monocyte and macrophage lineage known as osteoclasts
  • In local osteolytic hypercalcemia, the RANKL/RANK interaction results in excessive osteoclast activation leading to enhanced bone resorption and thus hypercalcemia
  • In addition, osteoclast activation is also mediated by malignancy secreted cytokines, including interleukin-1, initially termed “osteoclast stimulating factor”
  • Macrophage inflammation protein 1-alpha (MIP 1-alpha)
  • hypercalcemia is through extra-renal 1,25-dihydroxyvitamin D (calcitriol) production
  • 1% of cases
  • increased production of 1,25-dihydroxyvitamin D occurs nearly exclusively in Hodgkin and non-Hodgkin lymphoma with case reports of the same in ovarian dysgerminoma
  • 1-α-hydroxylase in the kidney, a process regulated by PTH
  • in 1,25-dihydroxyvitamin D induced hypercalcemia, malignant cells likely recruit and induce adjacent macrophages to express 1-α-hydroxylase, converting endogenous calcidiol into calcitriol.31 Calcitriol then binds to receptors in the intestine leading to heightened enteric calcium reabsorption with resultant hypercalcemia
  • this mechanism of disease is best conceptualized as an absorptive form of hypercalcemia
  • Ectopic production of PTH by malignant cells has been described in a handful of cases involving cancer of the ovary and lung, as well as neuroendocrine tumors and sarcoma
  • primary hyperparathyroidism and malignancy comprising nearly 90% of cases of hypercalcemia
  • an initial panel consisting of PTH, PTHrP, phosphorus, 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D should be obtained
  • Lymphoma, a hypercalcemia due to 1,25-dihydroxyvitamin D mediated pathways, is implied by elevations in 1,25-dihydroxyvitamin D without concomitant elevations in 25-hydroxyvitamin D. In such cases, PTH is low and PTHrP undetectable
  • Treatment of hypercalcemia of malignancy is aimed at lowering the serum calcium concentration by targeting the underlying disease, specifically by inhibiting bone resorption, increasing urinary calcium excretion, and to a lesser extent by decreasing intestinal calcium absorption
  • mildly symptomatic disease
  • marked symptoms
  • hydration with isotonic fluid (if admitted), avoidance of thiazide diuretics, and a low-calcium diet
  • denosumab
  • Denosumab is an RANKL antibody that inhibits osteoclast maturation, activation, and function
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    hypercalcemia in cancer and treatments.
Nathan Goodyear

Genetic Determinants of Serum Testosterone Concentrations in Men - 0 views

  • mean serum testosterone concentrations were found to be lower in men with GG than in those with TT genotype for rs12150660
  • men with the CT genotype for rs6258 had lower serum testosterone concentrations than those with CC genotype.
  • The two autosomal SNPs identified by GWAS had a significant influence on the risk of having low serum testosterone (serum testosterone <300 ng/dl) in both the discovery and the replication cohorts with a combined odds ratio (OR) per minor allele of 0.72 (95% CI, 0.65 – 0.79) and 2.7 (95% CI, 2.1 – 3.5) for rs12150660 and rs6258, respectively
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  • The risk of having low serum testosterone concentrations increased by the number of risk alleles with an OR of 1.62 (95% CI, 1.41 – 1.86) for each risk allele (Figure S4). Low serum testosterone concentrations were 6.5-times more prevalent in men with ≥3 risk alleles (30.1% prevalence of low serum testosterone) compared to men without any risk allele (4.6% prevalence of low serum testosterone;
  • SNP rs5934505 was associated with serum testosterone without SHBG-adjustment (combined p-value of 1.7×10−9) and with free testosterone (combined p-value of 6.7×10−15), but not with SHBG
  • The mean serum testosterone and calculated free testosterone but not SHBG concentrations were lower in men with T genotype than in those with C genotype for rs5934505
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    Genetic SNP rs5934505 associated with lower total Testosterone and lower calculated free Testosterone.  No effects on SHBG.
Nathan Goodyear

Statins use and coronary artery plaque composition: Results from the International Mult... - 0 views

  • Statin use is associated with an increased prevalence and extent of coronary plaques possessing calcium
  • As compared with individuals not taking statins, those taking statins possessed a significantly higher prevalence of obstructive CAD, as well as higher numbers of vessels with obstructive CAD
  • non-calcified plaques (NCP)
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  • non-calcified (NCP), mixed (MP), or calcified (CP) plaque
  • statin use was each associated with a significantly higher prevalence of NCP, MP and CP
  • statin use was associated with increased presence of MP [odds ratio (OR) 1.46, 95% confidence interval (CI) 1.27–1.68, p < 0.001] and CP (OR 1.54, 95% CI 1.36–1.74, p < 0.001], but not NCP
  • statin use was associated with increasing numbers of coronary segments possessing MP and CP but not associated with increasing numbers of coronary segments possessing NCP
  • North America, Europe and Asia
  • A total of 6673 individuals (2413 on statin therapy and 4260 not on statin therapy) comprised the study population
  • we identified a strong association of statin use to coronary artery plaque features
  • statin use was associated with a differentially increased prevalence and extent of MP and CP
  • one potential unifying hypothesis is that rather than regression of coronary plaque, statins may contribute to the conversion of coronary plaque constituents, perhaps by conversion of NCP to plaque possessing calcium
  • Coronary computed tomographic angiography (CCTA)
  • Statin use was associated with a higher frequency of severe coronary artery stenoses as well as numbers of coronary vessels with obstructive CAD
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    Study finds statin therapy associated with increased coronary plaque with calcium.
Nathan Goodyear

Zadaxin (Thymalfasin): Uses, Dosage, Side Effects, Interactions, Warning - 0 views

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    Not an article, but a drug review of the medication Zadaxin, which is a commercial synthetic form of TA-1; Thymosin alpha 1 improved immunological parameters increased tumor response rates, and improved survival and quality of life
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DHSC adds Dexcom One transmitter to March 2023 Drug Tariff - 0 views

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    Department of Health of Social Care (DHSC) has confirmed that the Dexcom One Transmitter will be added to Part IXA of the March 2023 Drug Tariff. "Previously, patients were advised to obtain the free-of-charge Dexcom One transmitters directly from the pharmacies, without a prescription, as the original Drug Tariff application for the transmitter was unsuccessful," said the Pharmaceutical Services Negotiating Committee (PSNC) It has raised concerns with DHSC and Dexcom that these distribution arrangements for transmitters are unacceptable because they result in extra unfunded activity for community pharmacies. Both, DHSC and Dexcom acted upon these concerns by agreeing to add the Dexcom One transmitter to the Drug Tariff from March 2023. At the same time, Dexcom One CGM System (containing 1 sensor, 1 sensor applicator, 1 transmitter) will also be added to the March Drug Tariff.
Nathan Goodyear

Testosterone administration to elderly men increases skeletal muscle strength and prote... - 0 views

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    Testosterone given to elderly men with low "serum" testosterone shown to increase IGF-1 and increased muscle growth and strength.  So, this study shows that testosterone in men, seems to increase HGH production and thus increase IGF-1 production.  This may be the mechanism by which testosterone promotes muscle growth and increase in strength in men.
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Windows Technical Support Number 1 800 261 4071 - 0 views

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Nathan Goodyear

[Effects of testosterone on insulin r... [Zhonghua Yi Xue Za Zhi. 2006] - PubMed - NCBI - 0 views

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    Testosterone shown to improve GLUT 4 and IRS-1 expression with low dose short term therapy; in contrast, high dose, prolonged therapy shown to down regulate IRS-1 and GLUT 4 expression.  This shows the importance of using saliva for evaluation versus serum.  Serum testing routinely leads to over treatment with high dosages of testosterone.
Nathan Goodyear

Low Doses of Lipopolysaccharide and Minimally Oxidized Low-Density Lipoprotei... - 0 views

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    LPS and minimal oxidized LDL have synergistic effects on inflammatory signaling.  Together the two promote inflammatory signaling from macrophages at much lower levels than either one alone.  They do this through macrophage NF-KappaB and AP-1 pathways.  And this resultant inflammation promotes atherosclerosis.  Where does all this start?  our diet and our gut.
Nathan Goodyear

Intratumoral androgen biosynthesis in prostate cancer pathogenesis and response to therapy - 0 views

  • Additional studies have similarly found that prostate tissue levels of DHT in PCa patients treated with ADT therapy before prostatectomy declined by only ∼75% versus declines of ∼95% in serum levels
  • In a recent study in healthy men, treatment for 1 month with a GnRH antagonist to suppress testicular androgen synthesis caused a 94% decline in serum testosterone, but only a 70–80% decline in prostate tissue testosterone and DHT
  • progression to CRPC was associated with increased intratumoral accumulation or synthesis of testosterone.
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  • the intraprostatic synthesis of testosterone from adrenal-derived precursors likely accounts for the relatively high testosterone levels in prostate after ADT
  • In addition, AR activity in these cells is likely further enhanced by multiple mechanisms that sensitize AR to low levels of androgens
  • higher affinity ligand DHT (approximately eightfold higher affinity
  • type 2 5α-reductase (SRD5A2) being the major enzyme in prostate
  • reduce DHT to 5α-androstane-3α,17β-diol (3α-androstanediol; Ji et al. 2003, Rizner et al. 2003), which is then glucuronidated to form 3α-androstanediol glucuronide by the enzymes UDP glycosyltransferase 2, B15 (UGT2B15) or UGT2B17
  • DHT in prostate is inactivated by the enzyme AKR1C2, which is also termed 3α-hydroxysteroid dehydrogenase type 3 (3α-HSD type 3
    • Nathan Goodyear
       
      The metabolite 3-alpha androstanediol is NOT inactive as this author states.  This DHT metabolite actually can stimulate  ER alpha receptors in the prostate.
  • AKR1C1, is also expressed in prostate. However, in contrast to AKR1C2, it converts DHT primarily to 5α-androstane-3β,17β-diol (3β-androstanediol; Steckelbroeck et al. 2004), which is a potential endogenous ligand for the estrogen receptor β
  • Significantly, intraprostatic testosterone levels were not substantially reduced relative to controls with normal serum androgen levels, although DHT levels were reduced to 18% of controls
  • testosterone levels in many of the CRPC samples were actually increased relative to control tissues (Montgomery et al. 2008). While DHT levels were less markedly increased, this may have reflected DHT catabolism
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    This article discusses the failure of androgen deprivation therapy and prostate cancer.  This failure is quite common.  The authors point to alpha-DHT as the primary mechanism through AR stimulation.  However, we know that DHT metabolites also stimulate estrogen receptors.
Nathan Goodyear

JISSN | Full text | International Society of Sports Nutrition position stand: creatine ... - 0 views

  • the energy supplied to rephosphorylate adenosine diphosphate (ADP) to adenosine triphosphate (ATP) during and following intense exercise is largely dependent on the amount of phosphocreatine (PCr) stored in the muscle
  • Creatine is chemically known as a non-protein nitrogen
  • It is synthesized in the liver and pancreas from the amino acids arginine, glycine, and methionine
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  • Approximately 95% of the body's creatine is stored in skeletal muscle
  • About two thirds of the creatine found in skeletal muscle is stored as phosphocreatine (PCr) while the remaining amount of creatine is stored as free creatine
  • The body breaks down about 1 – 2% of the creatine pool per day (about 1–2 grams/day) into creatinine in the skeletal muscle
  • The magnitude of the increase in skeletal muscle creatine content is important because studies have reported performance changes to be correlated to this increase
  • "loading" protocol. This protocol is characterized by ingesting approximately 0.3 grams/kg/day of CM for 5 – 7 days (e.g., ≃5 grams taken four times per day) and 3–5 grams/day thereafter [18,22]. Research has shown a 10–40% increase in muscle creatine and PCr stores using this protocol
  • Additional research has reported that the loading protocol may only need to be 2–3 days in length to be beneficial, particularly if the ingestion coincides with protein and/or carbohydrate
  • A few studies have reported protocols with no loading period to be sufficient for increasing muscle creatine (3 g/d for 28 days)
  • Cycling protocols involve the consumption of "loading" doses for 3–5 days every 3 to 4 weeks
  • Most of these forms of creatine have been reported to be no better than traditional CM in terms of increasing strength or performance
  • Recent studies do suggest, however, that adding β-alanine to CM may produce greater effects than CM alone
  • These investigations indicate that the combination may have greater effects on strength, lean mass, and body fat percentage; in addition to delaying neuromuscular fatigue
  • creatine phosphate has been reported to be as effective as CM at improving LBM and strength
  • Green et al. [24] reported that adding 93 g of carbohydrate to 5 g of CM increased total muscle creatine by 60%
  • Steenge et al. [23] reported that adding 47 g of carbohydrate and 50 g of protein to CM was as effective at promoting muscle retention of creatine as adding 96 g of carbohydrate.
  • It appears that combining CM with carbohydrate or carbohydrate and protein produces optimal results
  • Studies suggest that increasing skeletal muscle creatine uptake may enhance the benefits of training
  • Nearly 70% of these studies have reported a significant improvement in exercise capacity,
  • Long-term CM supplementation appears to enhance the overall quality of training, leading to 5 to 15% greater gains in strength and performance
  • Nearly all studies indicate that "proper" CM supplementation increases body mass by about 1 to 2 kg in the first week of loading
  • short-term adaptations reported from CM supplementation include increased cycling power, total work performed on the bench press and jump squat, as well as improved sport performance in sprinting, swimming, and soccer
  • Long-term adaptations when combining CM supplementation with training include increased muscle creatine and PCr content, lean body mass, strength, sprint performance, power, rate of force development, and muscle diameter
  • subjects taking CM typically gain about twice as much body mass and/or fat free mass (i.e., an extra 2 to 4 pounds of muscle mass during 4 to 12 weeks of training) than subjects taking a placebo
  • The gains in muscle mass appear to be a result of an improved ability to perform high-intensity exercise via increased PCr availability and enhanced ATP synthesis, thereby enabling an athlete to train harder
  • there is no evidence to support the notion that normal creatine intakes (< 25 g/d) in healthy adults cause renal dysfunction
  • no long-term side effects have been observed in athletes (up to 5 years),
  • One cohort of patients taking 1.5 – 3 grams/day of CM has been monitored since 1981 with no significant side effects
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    Nice review of the data, up to the publication date, on creatine.
Nathan Goodyear

Testosterone Deficiency, Cardiac Health, and Older Men - 0 views

  • Studies have shown pharmacological doses of testosterone to relax coronary arteries when injected intraluminally [39] and to produce modest but consistent improvement in exercise-induced angina and reverse associated ECG changes [40]. The mechanism of action is via blockade of calcium channels with effect of similar magnitude to nifedipine
    • Nathan Goodyear
       
      This directly refutes the recent studies (3) that Testosterone therapy increases cardiovascular events.
    • Nathan Goodyear
       
      Testosterone acts as a calcium channel blocker inducing vasodilation.
  • men with chronic stable angina pectoris, the ischaemic threshold increased after 4 weeks of TRT and a recent study demonstrates improvement continuing beyond 12 months [
  • Exercise capacity in men with chronic heart failure increased after 12 weeks
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  • Studies have shown an inverse relationship between serum testosterone and fasting blood glucose and insulin levels
  • Medications such as chronic analgesics, anticonvulsants, 5ARIs, and androgen ablation therapy are associated with increased risk of testosterone deficiency and insulin resistance
  • Women with T2D or metabolic syndrome characteristically have low SHBG and high free testosterone
    • Nathan Goodyear
       
      This stands in polar opposite of that with men.
  • Hypogonadism is a common feature of the metabolic syndrome
  • The precise interaction between insulin resistance, visceral adiposity, and hypogonadism is, as yet, unclear but the important mechanisms are through increased aromatase production, raised leptin levels, and increase in inflammatory kinins
  • levels of testosterone are reduced in proportion to degree of obesity
  • Men should be encouraged to combine aerobic exercise with strength training. As muscle increases, glucose will be burned more efficiently and insulin levels will fall. A minimum of 30 minutes exercise three times weekly should be advised
  • Testosterone increases levels of fast-twitch muscle fibres
  • By increasing testosterone, levels of type 2 fibres increase and glucose burning improves
  • Weight loss will increase levels of testosterone
  • studies now clearly show that low testosterone leads to visceral obesity and metabolic syndrome and is also a consequence of obesity
  • In the case of MMAS [43], a baseline total testosterone of less than 10.4 nmol/L was associated with a greater than 4-fold incidence of type 2 diabetes over the next 9 years
  • There is high level evidence that TRT improves insulin resistance
  • Low testosterone predicts increased mortality and testosterone therapy improves survival in 587 men with type 2 diabetes
  • A similar retrospective US study involved 1031 men with 372 on TRT. The cumulative mortality was 21% in the untreated group versus 10% ( ) in the treated group with the greatest effect in younger men and those with type 2 diabetes
  • the presence of ED has been shown to be an independent risk factor, particularly in hypogonadal men, increasing the risk of cardiac events by over 50%
  • A recent online publication on ischaemic heart disease mortality in men concluded optimal androgen levels are a biomarker for survival
  • inverse associations between low TT or FT (Table 2) and the severity of CAD
  • A recent 10 year study from Western Australia involving 3690 men followed up from 2001–2010 concluded that TT and FT levels in the normal range were associated with decreased all-cause and cardiovascular mortality, for the first time suggesting that both low and DHT are associated with all-cause mortality and higher levels of DHT reduced cardiovascular risk
  • TDS is associated with increased cardiovascular and all-cause mortality
  • The effect of treatment with TRT reduced the mortality rate of treated cohort (8.4%) to that of the eugonadal group whereas the mortality for the untreated remained high at 19.2%
  • hypogonadal men had slightly increased triglycerides and HDL
  • Men with angiographically proven CAD (coronary artery disease) have significantly lower testosterone levels [29] compared to controls ( ) and there was a significant inverse relationship between the degree of CAD and TT (total testosterone) levels
  • TRT has also been shown to reduce fibrinogen to levels similar to fibrates
  • men treated with long acting testosterone showed highly significant reductions in TC, LDL, and triglycerides with increase in HDL, associated with significant reduction in weight, BMI, and visceral fat
  • Low androgen levels are associated with an increase in inflammatory markers
  • A decline was noted in IL6 and TNF-alpha
  • In some studies, a decline in diastolic blood pressure has been observed, after 3–9 months [24, 26] and in systolic blood pressure
  • In the Moscow study, C-reactive protein was reduced by TRT at 30 weeks versus placebo
  • No studies to date show an increase in LUTS/BPH symptoms with higher serum testosterone levels
  • TRT has been shown to upregulate PDE5 [65] and enhance the effect of PDE5Is (now an accepted therapy for both ED and LUTS), it no longer seems logical to advice avoidance of TRT in men with mild to moderate BPH.
    • Nathan Goodyear
       
      What about just starting with normalization of Testosterone levels first.
  • Several meta-analyses have failed to show a link between TRT and development of prostate cancer [66] but some studies have shown a tendency for more aggressive prostate cancer in men with low testosterone
    • Nathan Goodyear
       
      And if one would have looked at their estrogen levels, I guarantee they would have been found to be elevated.
  • low bioavailable testosterone and high SHBG were associated with a 4.9- and 3.2-fold risk of positive biopsy
  • Current EAU, ISSAM, and BSSM guidance [1, 2] is that there is “no evidence TRT is associated with increased risk of prostate cancer or activation of subclinical cancer.”
  • Men with prostate cancer, treated with androgen deprivation, develop an increase of fat mass with an altered lipid profile
  • Erectile dysfunction is an established marker for future cardiovascular risk and the major presenting symptom leading to a diagnosis of low testosterone
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