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Nathan Goodyear

Semen analysis and sperm function tests: How much to test? - 0 views

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    good review of the data behind semen analysis and what is important to evaluate.
Nathan Goodyear

The Metabolic Syndrome - 0 views

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    Good review of the data looking at the relationship between MetS and cancer.
Nathan Goodyear

Antioxidants as Therapeutic Agents for Liver Disease - 0 views

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    This study concludes that evidence is small and inadequate despite consistent reductions of elevated liver enzymes.  The review of the data here includes both IV and oral therapy.  These modalities are not comparable.  IV vitamin C has been shown to reduce elevated liver enzymes where oral does not.
Nathan Goodyear

Gonadal Steroids and Body Composition, Strength, and Sexual Function in Men - NEJM - 0 views

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    This study confirms what we know about Testosterone, but this study finds that Estradiol aids libido and fat loss.  The conclusion on Estradiol I believe to be extremely premature.  First, it flies in the face of all the accumulative data on estradiol, second, what normal physiology is being replicated with goserelin???  Goserelin has been shown to decrease Prolactin which can effect libido also.  What about the potential there?  The men included in the study were described as "healthy".  So, you are taking "healthy" normal funcitoning men, throwing in a monkey wrench and looking at the effects of your monkey wrench.  Sorry, not physiologic.  In all my practice, I have seen one man with low Estradiol levels.  There is no reference to the hormone levels in the men preceding the suppression with goserelin.  This is a study that lacks application.
Nathan Goodyear

Testosterone and the Cardiovascular System: A Comprehensive Review of the Clinical Lite... - 0 views

  • Low endogenous bioavailable testosterone levels have been shown to be associated with higher rates of all‐cause and cardiovascular‐related mortality.39,41,46–47 Patients suffering from CAD,13–18 CHF,137 T2DM,25–26 and obesity27–28
  • have all been shown to have lower levels of endogenous testosterone compared with those in healthy controls. In addition, the severity of CAD15,17,29–30 and CHF137 correlates with the degree of testosterone deficiency
  • In patients with CHF, testosterone replacement therapy has been shown to significantly improve exercise tolerance while having no effect on LVEF
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  • testosterone therapy causes a shift in the skeletal muscle of CHF patients toward a higher concentration of type I muscle fibers
  • Testosterone replacement therapy has also been shown to improve the homeostatic model of insulin resistance and hemoglobin A1c in diabetics26,68–69 and to lower the BMI in obese patients.
  • Lower levels of endogenous testosterone have been associated with longer duration of the QTc interval
  • testosterone replacement has been shown to shorten the QTc interval
  • negative correlation has been demonstrated between endogenous testosterone levels and IMT of the carotid arteries, abdominal aorta, and thoracic aorta
  • These findings suggest that men with lower levels of endogenous testosterone may be at a higher risk of developing atherosclerosis.
  • Current guidelines from the Endocrine Society make no recommendations on whether patients with heart disease should be screened for hypogonadism and do not recommend supplementing patients with heart disease to improve survival.
  • The Massachusetts Male Aging Study also projects ≈481 000 new cases of hypogonadism annually in US men within the same age group
  • since 1993 prescriptions for testosterone, regardless of the formulation, have increased nearly 500%
  • Testosterone levels are lower in patients with chronic illnesses such as end‐stage renal disease, human immunodeficiency virus, chronic obstructive pulmonary disease, type 2 diabetes mellitus (T2DM), obesity, and several genetic conditions such as Klinefelter syndrome
  • A growing body of evidence suggests that men with lower levels of endogenous testosterone are more prone to develop CAD during their lifetimes
  • There are 2 major potential confounding factors that the older studies generally failed to account for. These factors are the subfraction of testosterone used to perform the analysis and the method used to account for subclinical CAD.
  • The biologically inactive form of testosterone is tightly bound to SHBG and is therefore unable to bind to androgen receptors
  • The biologically inactive fraction of testosterone comprises nearly 68% of the total testosterone in human serum
  • The biologically active subfraction of testosterone, also referred to as bioavailable testosterone, is either loosely bound to albumin or circulates freely in the blood, the latter referred to as free testosterone
  • It is estimated that ≈30% of total serum testosterone is bound to albumin, whereas the remaining 1% to 3% circulates as free testosterone
  • it can be argued that using the biologically active form of testosterone to evaluate the association with CAD will produce the most reliable results
  • English et al14 found statistically significant lower levels of bioavailable testosterone, free testosterone, and free androgen index in patients with catheterization‐proven CAD compared with controls with normal coronary arteries
  • patients with catheterization‐proven CAD had statistically significant lower levels of bioavailable testosterone
  • In conclusion, existing evidence suggests that men with CAD have lower levels of endogenous testosterone,13–18 and more specifically lower levels of bioavailable testosterone
  • low testosterone levels are associated with risk factors for CAD such as T2DM25–26 and obesity
  • In a meta‐analysis of these 7 population‐based studies, Araujo et al41 showed a trend toward increased cardiovascular mortality associated with lower levels of total testosterone, but statistical significance was not achieved (RR, 1.25
  • the authors showed that a decrease of 2.1 standard deviations in levels of total testosterone was associated with a 25% increase in the risk of cardiovascular mortality
  • the relative risk of all‐cause mortality in men with lower levels of total testosterone was calculated to be 1.35
  • higher risk of cardiovascular mortality is associated with lower levels of bioavailable testosterone
  • Existing evidence seems to suggest that lower levels of endogenous testosterone are associated with higher rates of all‐cause mortality and cardiovascular mortality
  • studies have shown that lower levels of endogenous bioavailable testosterone are associated with higher rates of all‐cause and cardiovascular mortality
  • It may be possible that using bioavailable testosterone to perform mortality analysis will yield more accurate results because it prevents the biologically inactive subfraction of testosterone from playing a potential confounding role in the analysis
  • The earliest published material on this matter dates to the late 1930s
  • the concept that testosterone replacement therapy improves angina has yet to be proven wrong
  • In more recent studies, 3 randomized, placebo‐controlled trials demonstrated that administration of testosterone improves myocardial ischemia in men with CAD
  • The improvement in myocardial ischemia was shown to occur in response to both acute and chronic testosterone therapy and seemed to be independent of whether an intravenous or transdermal formulation of testosterone was used.
  • testosterone had no effect on endothelial nitric oxide activity
  • There is growing evidence from in vivo animal models and in vitro models that testosterone induces coronary vasodilation by modulating the activity of ion channels, such as potassium and calcium channels, on the surface of vascular smooth muscle cells
  • Experimental studies suggest that the most likely mechanism of action for testosterone on vascular smooth muscle cells is via modulation of action of non‐ATP‐sensitive potassium ion channels, calcium‐activated potassium ion channels, voltage‐sensitive potassium ion channels, and finally L‐type calcium ion channels
  • Corona et al confirmed those results by demonstrating that not only total testosterone levels are lower among diabetics, but also the levels of free testosterone and SHBG are lower in diabetic patients
  • Laaksonen et al65 followed 702 Finnish men for 11 years and demonstrated that men in the lowest quartile of total testosterone, free testosterone, and SHBG were more likely to develop T2DM and metabolic syndrome.
  • Vikan et al followed 1454 Swedish men for 11 years and discovered that men in the highest quartile of total testosterone were significantly less likely to develop T2DM
  • authors demonstrated a statistically significant increase in the incidence of T2DM in subjects receiving gonadotropin‐releasing hormone antagonist therapy. In addition, a significant increase in the rate of myocardial infarction, stroke, sudden cardiac death, and development of cardiovascular disease was noted in patients receiving antiandrogen therapy.67
  • Several authors have demonstrated that the administration of testosterone in diabetic men improves the homeostatic model of insulin resistance, hemoglobin A1c, and fasting plasma glucose
  • Existing evidence strongly suggests that the levels of total and free testosterone are lower among diabetic patients compared with those in nondiabetics
  • insulin seems to be acting as a stimulant for the hypothalamus to secret gonadotropin‐releasing hormone, which consequently results in increased testosterone production. It can be argued that decreased stimulation of the hypothalamus in diabetics secondary to insulin deficiency could result in hypogonadotropic hypogonadism
  • BMI has been shown to be inversely associated with testosterone levels
  • This interaction may be a result of the promotion of lipolysis in abdominal adipose tissue by testosterone, which may in turn cause reduced abdominal adiposity. On the other hand, given that adipose tissue has a higher concentration of the enzyme aromatase, it could be that increased adipose tissue results in more testosterone being converted to estrogen, thereby causing hypogonadism. Third, increased abdominal obesity may cause reduced testosterone secretion by negatively affecting the hypothalamus‐pituitary‐testicular axis. Finally, testosterone may be the key factor in activating the enzyme 11‐hydroxysteroid dehydrogenase in adipose tissue, which transforms glucocorticoids into their inactive form.
  • increasing age may alter the association between testosterone and CRP. Another possible explanation for the association between testosterone level and CRP is central obesity and waist circumference
  • Bai et al have provided convincing evidence that testosterone might be able to shorten the QTc interval by augmenting the activity of slowly activating delayed rectifier potassium channels while simultaneously slowing the activity of L‐type calcium channels
  • consistent evidence that supplemental testosterone shortens the QTc interval.
  • Intima‐media thickness (IMT) of the carotid artery is considered a marker for preclinical atherosclerosis
  • Studies have shown that levels of endogenous testosterone are inversely associated with IMT of the carotid artery,126–128,32,129–130 as well as both the thoracic134 and the abdominal aorta
  • 1 study has demonstrated that lower levels of free testosterone are associated with accelerated progression of carotid artery IMT
  • another study has reported that decreased levels of total and bioavailable testosterone are associated with progression of atherosclerosis in the abdominal aorta
  • These findings suggest that normal physiologic testosterone levels may help to protect men from the development of atherosclerosis
  • Czesla et al successfully demonstrated that the muscle specimens that were exposed to metenolone had a significant shift in their composition toward type I muscle fibers
  • Type I muscle fibers, also known as slow‐twitch or oxidative fibers, are associated with enhanced strength and physical capability
  • It has been shown that those with advanced CHF have a higher percentage of type II muscle fibers, based on muscle biopsy
  • Studies have shown that men with CHF suffer from reduced levels of total and free testosterone.137 It has also been shown that reduced testosterone levels in men with CHF portends a poor prognosis and is associated with increased CHF mortality.138 Reduced testosterone has also been shown to correlate negatively with exercise capacity in CHF patients.
  • Testosterone replacement therapy has been shown to significantly improve exercise capacity, without affecting LVEF
  • the results of the 3 meta‐analyses seem to indicate that testosterone replacement therapy does not cause an increase in the rate of adverse cardiovascular events
  • Data from 3 meta‐analyses seem to contradict the commonly held belief that testosterone administration may increase the risk of developing prostate cancer
  • One meta‐analysis reported an increase in all prostate‐related adverse events with testosterone administration.146 However, when each prostate‐related event, including prostate cancer and a rise in PSA, was analyzed separately, no differences were observed between the testosterone group and the placebo group
  • the existing data from the 3 meta‐analyses seem to indicate that testosterone replacement therapy does not increase the risk of adverse cardiovascular events
  • the authors correctly point out the weaknesses of their study which include retrospective study design and lack of randomization, small sample size at extremes of follow‐up, lack of outcome validation by chart review and poor generalizability of the results given that only male veterans with CAD were included in this study
    • Nathan Goodyear
       
      The authors here present Total Testosterone as a "confounding" value
    • Nathan Goodyear
       
      This would be HSD-II
  • the studies that failed to find an association between testosterone and CRP used an older population group
  • low testosterone may influence the severity of CAD by adversely affecting the mediators of the inflammatory response such as high‐sensitivity C‐reactive protein, interleukin‐6, and tumor necrosis factor–α
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    Good review of Testosterone and CHD.  Low T is associated with increased all cause mortality and cardiovascular mortality, CAD, CHF, type II diabetes, obesity, increased IMT,  increased severity of CAD and CHF.  Testosterone replacement in men with low T has been shown to improve exercise tolerance in CHF, improve insulin resistance, improve HgbA1c and lower BMI in the obese.
Nathan Goodyear

Thyroid Function Within the Normal Range and the Risk of Depression: A Population-Based... - 0 views

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    Elderly individuals with the lowest normal TSH values were found to be associated with increased depressive symptoms.  These patients were clearly not hyperthyroid.  This fits with other data that points to increased inflammation and reduced TSH levels.  Increased inflammation is associated with increased depression.
Nathan Goodyear

High Estrogen in Men After Injectable Testo... [Am J Mens Health. 2014] - PubMed - NCBI - 0 views

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    Again, Testosterone and here Estradiol are merely there for libido and sex.  What tunnel vision?!  What about hsCRP?  What about fibrinogen?  What about IL-1beta?  What about TNF-alpha?  These inflammatory cytokines have all been reported to elevate as a result of estrogen production in men.   And PSA?  No mention of it here.   This linear, tunnel vision thinking on hormones has got to stop! The study points out that all clients were using AIs and SERMs irregardless of whether they had elevated estrogens or not.  That is not a well designed study.  One group should have had AI's if elevated estrogens were present and another group should not--this would compare the effects of aromatase activity.  Second, this was simply a retrospective chart review.  Third, a 50% conversion of 34,000 + men is very high when you look at the literature.  Fourth, they point to gynecomastia as a means of negative?  The cardiovascular implications are more significant.  These studies just seem to focus on superficial things.  Fifth, did libido problems exist before?  What were the free levels?   This falls in the paucity of data (2 studies) that point to excessive lowering of estradiol effecting libido and sexual performance.
Nathan Goodyear

Huperzine A in the Treatment of Alzheimer's Disease and Vascular Dementia: A Meta-Analysis - 0 views

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    Good review of the data on Huperzine A and Alzheimer's dementia.
Nathan Goodyear

The Benefits and Harms of Systemic Dehydroepiandrosterone (DHEA) in Postmenopausal Wome... - 0 views

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    Review of the data points to poor quality of evidence dealing with DHEA in post-menopausal women with normal adrenal function.  Yet if DHEA is low, which is >95% produced by adrenals in women, then how can the adrenal function be "normal".   The meta-analysis found no improvement in libido and/or sexual function, and no improvement in lipids, glucose, weight... was noted.  Essentially not positive or negative effects were noted.  Abstract only available here, so dosage is a question.
Nathan Goodyear

Testicular Synthesis and Vitamin D Action: The Journal of Clinical Endocrinology & Meta... - 0 views

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    Cholecalciferol (vitamin D3) was found to increase male Testosterone production in cell culture model.  This fits with other data that low vitamin D and low T often go hand in hand.  This study actually shows improved D levels increase Testicular Testosterone production, though in cell culture.
Nathan Goodyear

Androgen Therapy in Women: A Reappraisal: An Endocrine Society Clinical Practice Guidel... - 0 views

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    data on androgen therapy in women is sparse at best.  The conclusion here is suspect: "evidence supports the short-term efficacy and safety of high physiological doses of T" for women with with hypoactive sexual desire, yet the same authors recommend against long-term therapy.  How do those 2 go together???  They don't.  Support with physiologic Testosterone when appropriate testing reveals low T and symptoms support the same.  This is a practice guideline that lacks evidence to strongly back it up because so little evidence exists.  Practice guidelines are for lazy physicians.
Nathan Goodyear

Diet-induced obesity and low testosterone increase neuroinflammation and impair neural ... - 0 views

  • both obesity and low testosterone are also risk factors for neural dysfunction, including cognitive impairment [58–61] and development of AD
  • Levels of obesity and testosterone are often inversely correlated
  • diet-induced obesity causes significant metabolic disturbances and impairs central and peripheral nervous systems.
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  • both obesity and low testosterone are linked with promotion of inflammatory pathways [70–72] and exert harmful actions on the central [73–75] and peripheral [29,76] nervous systems
  • In general, obesity-related changes were worsened by low testosterone and improved by testosterone treatment; however, this relationship was not statistically significant in several instances. Further, our data suggest that a common pathway that may contribute to obesity and testosterone effects is regulation of inflammation
  • fasting blood glucose levels were independently and additively increased by GDX-induced testosterone depletion and high-fat diet
  • testosterone treatment significantly reduced fasting glucose under both the normal and high-fat diets, demonstrating potential therapeutic efficacy of testosterone supplementation
  • fasting insulin, insulin resistance (HOMA index), and glucose tolerance, low testosterone tended to exacerbate and or testosterone treatment improved outcomes.
  • testosterone status did not significantly affect body weight
  • testosterone’s effects likely do not indicate an indirect result on adiposity but rather regulatory action(s) on other aspects of metabolic homeostasis
  • Prior work in rodents has shown diet-induced obesity induces insulin resistance in rat brain [63] and that testosterone replacement improves insulin sensitivity in obese rats [64]. Our findings are consistent with the human literature, which indicates that (i) testosterone levels are inversely correlated to insulin resistance and T2D in healthy [30,65] as well as obese men [66], and (ii) androgen therapy can improve some metabolic measures in overweight men with low testosterone
  • it has been shown that TNFα has inhibitory effects on neuron survival, differentiation, and neurite outgrowth
  • Our data demonstrate that low testosterone and obesity independently increased cerebrocortical mRNA levels of both TNFα and IL-1β
  • Testosterone status also affected metabolic and neural measures
  • many beneficial effects of testosterone, including inhibition of proinflammatory cytokine expression
  • neuroprotection [80,81], are dependent upon androgen receptors, the observed effects of testosterone in this study may involve androgen receptor activation
  • testosterone can be converted by the enzyme aromatase into estradiol, which is also known to exert anti-inflammatory [82] and neuroprotective [83] actions
  • glia are the primary sources of proinflammatory molecules in the CNS
  • poorer survival of neurons grown on glia from mice maintained on high-fat diet
  • Since testosterone can affect glial function [86] and improve neuronal growth and survival [87–89], it was unexpected that testosterone status exhibited rather modest effects on neural health indices with the only significant response being an increase in survival in the testosterone-treated, high-fat diet group
  • significantly increased expression of TNFα and IL-1β in glia cultures derived from obese mice
  • testosterone treatment significantly lowered TNFα and IL-1β expression to near basal levels even in obese mice, indicating a protective benefit of testosterone across diet conditions
  • IL-1β treatment has been shown to induce synapse loss and inhibit differentiation of neurons
  • Testosterone status and diet-induced obesity were associated with significant regulation of macrophage infiltration
  • testosterone prevented and/or restored thermal nociception in both diet groups
  • a possible mechanism by which obesity and testosterone levels may affect the health of both CNS and PNS
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    Study points to obesity and low Testosterone contribution of neuroinflammation.  No effect of body weight was seen with TRT.  This animal model found similar positive effects of TRT in insulin sensitivity.  Obesity and low T increase inflammatory cytokine production: this study found an increase in TNF-alpha and IL-1beta and TRT reduced TNF-alpha and IL-1beta to near base-line.  Testosterone is neuroprotective and this study reviewed the small volume of evaded that pointed to benefit from estradiol.  Testosterone's effect on glial survival was positive but not significant.  Obesity and low T were found to be associated with increased macrophage infiltration in the PNS with increased TNF-alpha and IL-1beta.   Testosterone therapy improved peripheral neuropathy via its positive effects on nocicieption.
Nathan Goodyear

Arginine and Citrulline A Review of Their Safety and Efficacy for Erectile Dysfunction ... - 0 views

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    nice review on Arginine + citrulline in ED.  Data is limited, but studies suggest improvement with individual therapy.  
Nathan Goodyear

Hormone Therapy, Estrogen Metabolism, and Risk of Breast Cancer in the Women's Health I... - 0 views

  • These results demonstrate that although 16α-OHE1 was increased more by E+P than by E-alone, the increase in the 2:16 ratio was similar for both HT regimens, due to ~4-fold greater increase in 2OHE-1 than 16α-OHE1 for both HT regimens
  • baseline and 1 year change in 16α-OHE1 showed little relationship to incident breast cancer
  • higher baseline 2-OHE1 and the 2:16 ratio were modestly associated with higher odds of incident breast cancer, but larger 1 year increase in 2-OHE-1 and the 2:16 ratio were also weakly associated with lower odds of breast cancer
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    Good review of the data from the WHI-HT on estrogen metabolites and breast cancer risk.  Increased 2-OHestrone and 2:16 ratio without statistical significance reached.
Nathan Goodyear

JAMA Network | JAMA Surgery | Long-term Metabolic Effects of Laparoscopic Sleeve Gastre... - 0 views

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    This study reveals what is wrong with a lot of the "standard practice" and literature in medicine today.  At 5 years, almost 50% of weight loss with gastric sleeve is regained--defined as excess weight loss (only 50% weight loss of excess weight).  That is a terrible 5 year outcome; not to mention the definition of success.  Even at 3 years, 31% had regained their "excess weight".  Add to that, the numbers of patients that followed up was terrible.  This poor follow up points to worse data outcomes than this study claims.
Nathan Goodyear

Oxytrex Minimizes Physical Dependence While Providing Effective Analgesia: A Randomized... - 0 views

  • Active treatment groups attained comparable analgesia despite significantly lower drug use
  • preclinical data also show a suppression of opioid tolerance and dependence
  • Previous clinical data have shown ultralow-dose naltrexone enhances and prolongs oxycodone analgesia,
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  • A cellular mechanism of action has been demonstrated to be the prevention of aberrant G protein signaling by mu opioid receptors caused by chronic opioid administration
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    low dose naltrexone improves pain control and reduced opioid addiction
Nathan Goodyear

Wiley Online Library: Book Abstract - 0 views

  • In the relatively uncommon circumstance of vaccine matching the viral circulating strain and high circulation, 4% of unvaccinated people versus 1% of vaccinated people developed influenza symptoms (risk difference (RD) 3%
  • The corresponding figures for poor vaccine matching were 2% and 1% (RD 1, 95% CI 0% to 3%).
  • Vaccination had a modest effect on time off work and had no effect on hospital admissions or complication rates
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  • Influenza vaccines have a modest effect in reducing influenza symptoms and working days lost. There is no evidence that they affect complications, such as pneumonia, or transmission.
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    exhaustive review of the flu vaccine data reveals VERY poor matching of vaccine, poor prevention of flu symptoms, and only modest effect on reduction in hospital admission or complication rates.   Final conclusion: "There is no evidence that they affect complications, such as pneumonia, or TRANSMISSION.
Nathan Goodyear

Evaluation, Treatment, and Prevention of Vitamin D Deficiency: an Endocrine Society Cli... - 0 views

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    the Endocrine Society clinical practice guideline to not screen for vitamin D deficiency, proves that this organization cannot be looked to for reliable analysis of scientific data
Nathan Goodyear

Nonalcoholic Fatty Liver Disease - 0 views

  • aracterized by clinical and laboratory data similar to those found in diabetes and obesity. NAF
  • We concluded that NAFLD, in the presence of normoglycemia and normal or moderately increased body weight, is ch
  • aracterized by clinical and laboratory data similar to those found in diabetes and obesity. NAF
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  • LD may be considered an additional feature of the metabolic syndrome, with specific hepatic insulin resistance
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    Fatty Liver is component of Metabolic Syndrome
Nathan Goodyear

Testosterone therapy for reduced libido in women - 0 views

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    Good review of the data on Testosterone, libido, Testosterone therapy in women, and safety of Testosterone therapy in women.
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