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Nathan Goodyear

Low Free Testosterone Is Associated with Hypogonadal Signs and Symptoms in Men with Nor... - 0 views

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    hormones are best evaluated in toto.  For men, the story doesn't begin/end with total Testosterone.  New study finds that low free Testosterone (calculated) is associated with symptoms of low Testosterone despite normal total testosterone levels.
Nathan Goodyear

http://press.endocrine.org/doi/pdf/10.1210/jc.2014-1872 - 0 views

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    New study finds Testosterone therapy provides less than statistical significant improvement in constitutional/sexual symptoms, in obese men with type II diabetes with symptoms classified as mild-moderate with modest reductions in Total Testosterone.  This study highlights that low Testosterone is a biomarker of poor health and multiple comorbidities and that simply adding in Testosterone therapy will not cure all male woes.  The authors did state that ED and low T are separate issues and I will differ with them on this--they are in fact link.  This association may vary between individuals, but to flatly state they are completely separate issues is devoid of the fact that testosterone has been shown to reduce inflammatory cytokines and improve PDE5 therapy.  
Nathan Goodyear

Endocrinology of the Aging Male - 0 views

  • All steps beyond the formation of pregnenolone take place in the smooth endoplasmic reticulum
  • Cytochrome P450 enzyme, CYP11A is located on the inner mitochondrial membrane and catalyses the rate limiting step of pregnenolone synthesis
  • Estrogen and related steroids, thyroid hormone and insulin increase SHBG levels.
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  • SHBG decreases in response to androgens, and in the presence of hypothyroidism, and insulin resistance.
  • Plasma SHBG levels tend to increase with increasing age
  • The apparent metabolic clearance rate of testosterone is decreased in elderly as compared to younger men
  • Testosterone circulates predominantly bound to the plasma proteins SHBG and albumin, with high and low affinity respectively
  • Testosterone is secreted in a pulsatile fashion
  • Current clinical guidelines suggest at least two measurements
  • In adult men, there is a well-documented diurnal variation (particularly in younger subjects) in testosterone levels, which are highest in the early morning and progressively decline throughout the day to a nadir in the evening
  • In older men, the diurnal variation is blunted
  • it is standard practice for samples to be obtained between 0800 and 1100 h.
  • Testosterone and DHEA decline, whereas LH, FSH, and SHBG rise
  • DHT remains constant despite the decline of its precursor testosterone
  • Longitudinal studies show an average annual decline of 1–2% total testosterone levels, with decline in free testosterone more rapid because of increases in SHBG with aging
  • Massachusetts Male Aging Study (MMAS) data show DHEA, DHEAS, and Ae declining at 2–3% per year
  • DHT showed no cross-sectional age trend
  • Androstanediol glucuronide (AAG) declined cross-sectionally with age in the MMAS sample, at 0.6% per year
  • The EMAS data show that, consistent with the longitudinal findings of MMAS (Figure 1), the core hormonal pattern with increasing age is suggestive of incipient primary testicular dysfunction with maintained total testosterone and progressively blunted free testosterone associated with higher LH
    • Nathan Goodyear
       
      This author proves the point in the review of these two studies, that TT may remain constant in aging men, however, FT drops.
  • obesity impairs hypothalamic/pituitary function
  • Androgen deprivation in men with prostate cancer has been associated with increased insulin resistance, worse glycemic control, and a significant increase in risk of incident diabetes
  • Low serum testosterone is associated with the development of metabolic syndrome 116, 117 and type 2 diabetes. 118 SHBG has been inversely correlated with type 2 diabetes
  • Improvement in insulin sensitivity with testosterone treatment has been reported in healthy 121 and diabetic 122 adult men
  • In studies conducted in men with central adiposity, testosterone has been shown to inhibit lipoprotein lipase activity in abdominal adipose tissue leading to decreased triglyceride uptake in central fat depots. 123
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    great review of hormone changes associated with aging in men.
Nathan Goodyear

Comparison of salivary versus serum testos... [Menopause. 2009 Jul-Aug] - PubMed - NCBI - 0 views

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    this study looked at salivary testosterone to serum testosterone and found poor correlation.  One major problem with this study is the significantly smaller amount (10 fold) of testosterone in women than men in healthy individuals.  This study took place in postmenopausal women, which would have significantly lower levels than healthy women.  They also don't discuss the pitfalls of equilibrium dialysis of serum free testosterone.  Another major flaw is the mere logic of looking at serum for tissue activity.   What is the correlation between serum levels and tissue activity.  There is tremendous assumptions being undertaken that serum levels of testosterone whether total or free translate to genomic or non-genomic signaling.  I also wonder if newer techniques using Mass Spec can better detect the typically pico levels of testosterone in women's saliva?  This study does nothing to dissuade the use of salivary testing.
Nathan Goodyear

Effect of Testosterone Replacement Therapy on Cognitive Performance and Depression in M... - 0 views

  • Azad et al [15] used single photon emission computed tomography and showed that, after 3~5 weeks of TRT, cerebral perfusion was increased in the midbrain and the superior frontal gyrus in seven men with hypogonadism
  • After 12~14 weeks, increased perfusion was still observed in the midbrain as well as in the midcingulate gyrus
  • TDS patients who received TRT showed significant improvement in cognitive function only if mild cognitive impairment was present at baseline
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  • Cherrier et al [17] evaluated a sample of 32 subjects, which included 17 men with mild cognitive impairment and 15 with Alzheimer's disease. At the 6-week follow-up, patients who received TRT showed significantly better scores regarding spatial memory, constructional abilities, and verbal memory compared to those noted in the placebo group. Taken together, these results suggest that TRT has a beneficial effect on cognitive function
  • TRT improved mood and well-being, and reduced fatigue and irritability in hypogonadal men
  • The study by Pope et al [20] involved men with depression refractory to standard anti-depressants, and found that TRT lowered the Hamilton Depression score,
  • depression tends to increase as testosterone levels decrease [21], it is highly likely that TRT improved symptoms of depression by increasing testosterone levels.
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    men with Testosterone <300 ng/dl with levels after 8 months of therapy achieving +680 ng/dl.
Nathan Goodyear

Redefining Metabolic Syndrome in Men (July 2012) Townsend Letter for Doctors & Patients - 0 views

  • Approximately 95% to 98% of testosterone is bound to a carrier protein at any given time, leaving just the remaining 2% to 5% as completely unbound and available for tissues to use
  • most serum laboratories offer a free testosterone level, which is a calculated value based on SHBG levels or determined with equilibrium dialysis
  • the hormone enters the salivary gland by passive diffusion
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  • Testosterone has a known age-related decline, and total levels typically drop by approximately 1.6% per year beginning for most men in their 30s
  • As estrogen levels rise, they prompt the body to produce more SHBG, which in turn has a higher binding affinity for testosterone, and drives the unbound fraction of the testosterone pool down even further
  • When the increase in SHBG is taken into account, the age-related decline in the level of hormone that can be used by the body is closer to 2% to 3% per year.
  • Stinging nettle (Urtica dioica), an herb commonly used for allergies, can also be employed to bind to SHBG, which leaves more testosterone available to tissues
  • Leptin, an adipose-derived peptide hormone that regulates appetite and metabolism, has been shown to directly inhibit testosterone production in animal models
  • tumor necrosis factor alpha (TNF-alpha) and interleukin-1 (IL-1) further inhibit Leydig cell testosterone production
  • Natural aromatase inhibitors include the bioflavonoids chrysin and luteolin
  • Zinc deficiency causes an upregulation of the aromatase enzyme
  • Testosterone reduces lipoprotein lipase (LPL) activity
  • there are several herbs that can work to boost testosterone levels, including longjack (Eurycoma longifolia), horny goat weed (Epimedium grandiflorum), and tribulus (Tribulus terrestris).
  • the majority of the hormone is bound to carrier proteins including sex hormone binding globulin (SHBG) and albumin
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    nice and short review on testosterone and men's  health.
Nathan Goodyear

Longitudinal Effects of Aging on Serum Total and Free Testosterone Levels in Healthy Me... - 0 views

  • NUMEROUS CROSS-SECTIONAL INVESTIGATIONS have demonstrated lower concentrations of circulating testosterone (T) and/or free T in older men
  • Two small-scale longitudinal investigations have observed decreases, with aging, in total T
  • T levels decline at a more or less constant rate, with age, in men, with no period of accelerated decline
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  • aging in men is associated with decreases in bone mineral density (BMD) (18, 19), lean body and muscle mass
  • strength (22, 23) and aerobic capacity (24), as well as with increases in total and abdominal body fat, low-density lipoprotein cholesterol, and/or low-density lipoprotein/high-density lipoprotein cholesterol ratios (25, 26, 27, 28), all of which also occur in nonelderly hypogonadal men
  • Most (1, 5, 6, 7, 8, 9), but not all (10, 11, 12), cross-sectional studies have demonstrated a decrease, with age, in total T in men
    • Nathan Goodyear
       
      FAI: 100 x total Testosterone nmol/L/SHBG nmol/L
    • Nathan Goodyear
       
      These numbers do point to an increase in ng/dl decline in Total Testosterone with increasing age (decade group)
  • total T, but not free T index, tended to decrease with greater BMI is consistent with prior studies showing that obesity is associated with decreases in both SHBG and total T, with an unchanged T-to-SHBG ratio
  • The conventional definition for T levels is statistical (values more than 2 sd below the mean), rather than functional. Such a definition does not reflect clinical realities, such as the existence of characteristic individual set points for circulating hormone levels, below which one, but not another, individual may develop metabolic changes of hormone deficiency; nor does it address the concept of reserve capacity, the possibility that persons with hormone levels 2 sd below the population mean still may have adequate hormone concentrations to meet their metabolic needs.
    • Nathan Goodyear
       
      good explanation of problems with just using a number to define low T
  • both T and free T index (a calculated value related to free or bioavailable T) decreased progressively at a rate that did not vary significantly with age, from the third to the ninth decades.
  • contrasts with other studies showing diminished free, as well as total, T in with increasing total (48) or abdominal (49) obesity in men.
  • Our analysis of date-adjusted T and free T index levels, by decade, showed that relatively high numbers of older men in this generally healthy population had at least one hypogonadal value (defined as below the 2.5th percentile for young men)
  • The issue of how properly to define hypogonadism, or indeed any hormone deficiency, remains problematic
  • The decrease in free T index was somewhat steeper than that of total T, owing to a trend for an increase in SHBG with age
  • LH for gonadal function
  • It would clearly be better to define the lower limit of normal for a hormone as: the blood level at which metabolic and/or clinical sequelae of hormone deficiency begin to appear, or the level below which definite benefits can be demonstrated for hormone supplementation for a significant proportion of the population
  • an effect of aging to lower both total and bioavailable circulating T levels at a relatively constant rate, independent of obesity, illness, medications, cigarette smoking, or alcohol intake
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    Article highlights the problems with the definition of low T.  This article finds consistent decline in Total Testosterone and FAI with increasing age groups, with a significant portion of men > 60 meeting the required levels for "low T".  This study found a decrease in total T and FAI at a consistent rate independent of variables, such as BMI.    This study did find a decrease in SHBG and total T with obesity; in contrast to other studies.
Nathan Goodyear

Low Free Testosterone Is Associated with Hypogonadal Signs and Symptoms in Men with Nor... - 0 views

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    low free Testosterone, though calculated in this study, found to be associated with low T symptoms despite normal total Testosterone.  Though the "normal" total Testosterone in this study is abnormal low in other studies.  Only abstract available.
Nathan Goodyear

Testosterone deficiency is associated with increased risk of mortality and testosterone... - 0 views

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    Men with type II diabetes have lower Testosterone levels when compared to none diabetics.  This study found an increased mortality with low T in those with type II Diabetes.  The main association was found with bioavailable Testosterone.  Total Testosterone is proving useless as a functional tool.  Additionally, Testosterone therapy reduced mortality in those with Diabetes.
Nathan Goodyear

The prevalence of hypogonadism in diabetic men in Isfahan Endocrine and Metabolism Rese... - 0 views

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    Incidence of Low Testosterone very high in men with Diabetes in Iran.  This was the case whether Total Testosterone, calculated free Testosterone, calculated Biologic Testosterone, or SHBG was used.
Nathan Goodyear

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

  • 2.1 standard deviations in total testosterone was associated with a 25% increase in mortality
  • Erectile dysfunction is an established marker for future cardiovascular risk and the major presenting symptom leading to a diagnosis of low testosterone
  • There is a considerable body of evidence that low testosterone is associated with increased cardiovascular and cancer mortality
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  • There is considerable evidence of modest cardiac and metabolic benefits that are shown to reduce cardiovascular risk plus sexual, mood, and quality of life changes associated with restoring testosterone levels
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    low Testosterone is associated with increased mortality in men and Testosterone therapy in men with low T is associated with a reduction in mortality in men.
Nathan Goodyear

Differential Effects of Dehydroepiandrosterone and Testosterone in Prostate and Colon C... - 0 views

  • Several studies indicate that DHEA may enhance cancer-promoting activities in several prostate cancer cell lines acting as agonist or antagonist for the intracellular AR
  • the estrogenic metabolites of DHEA, 5a-androstane-3b, 17b-diol (3b-Adiol) and E2 bind to estrogen receptors but not to AR
  • no specific receptor has been identified for DHEA
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  • Different members of neurotrophins are expressed during cancer progression, suggesting their involvement in cell proliferation, anoikis protection, and malignancy
  • Regulation of the apoptotic machinery in prostate and colon cancer cells by testosterone occurs rapidly and is initiated at the plasma membrane level through specific membrane-binding sites not involving the classical cytoplasmic AR
  • testosterone exerts potent regulatory effects on prostate and colon cancer cell apoptosis
  • Testosterone increased cell death in a dose-dependent manner
  • testosterone antagonizes the prosurvival effects of DHEA in neuronal cells, blocking its binding to NGF receptors
  • treatment of cells with DHEA exerted a strong antiapoptotic effect,
  • Androgens hold a central role in prostate and colon cancer biology
  • elevated levels of DHEA or its sulfate ester DHEA-sulfate in young adults are associated to low incidence of androgen-dependent tumors
  • DHEA may play a protective role in young prostate
  • The decline of DHEA with aging may contribute to prostate cancer progression associated with advanced age
  • DHEA is an effective antiapoptotic factor, reversing the serum deprivation-induced apoptosis in prostate cancer cells (DU145 and LNCaP cell lines) as well as in colon cancer cells
  • NGF appears to exert similar antiapoptotic actions in both prostate and color cancer cells
  • exposure of prostate DU145 and colon Caco2 cancer cells to testosterone totally blocked the protective effects of both DHEA and NGF. These findings suggest that testosterone acts as an antagonist of DHEA and NGF
  • These findings support the hypothesis that testosterone may inhibit cancer cell growth by antagonizing the proliferative, antiapoptotic effects of endogenous factors, such as DHEA or NGF, in the case of prostate and colon cancer cells
  • intratumor hormonal microenvironment may play a critical role in tumor progression.
  • The paracrine interactions of androgens with locally produced NGF may define tumor cell fate
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    Full article of previously posted abstract.  Cancers are unique.  Not all cancers are alike.  Whether they are tissue specific or not, cancers are unique.  This article describes the uniqueness of DHEA and Testosterone cancer, with particular attention to colon.
Nathan Goodyear

Total and free testosterone concentrat... [Clin Endocrinol (Oxf). 2012] - PubMed - NCBI - 0 views

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    Testosterone levels appear to be more of a biomarker of poor health in older men that are obese with diabetes.  More of these men had low free Testosterone (calc) versus Total Testosterone.  Using QOL questionnaires, weak correlation (not statistically significant) with androgen deficiency symptoms and ED were found.
Nathan Goodyear

Morning free and total testosterone in HIV-infected men: implications for the assessmen... - 0 views

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    low T is found in 20-70% of men with HIV.  What is interesting about this article is that Total Testosterone was found to be a poor assessment of biological active Testosterone.  Free Testosterone assessed in the am was shown to be a better functional assessment in these men.  Serum is a poor choice though.  The process of equilibrium dialysis to calculate free Testosterone is filled with variables that will effect reliability.  Increases SHBG was found associated.
Nathan Goodyear

Low Levels of Free Testosterone Correlated wi... [Horm Metab Res. 2014] - PubMed - NCBI - 0 views

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    Interesting study looked at Total Testosterone (TT) and free Testosterone (FT) in older men in BMD assessment.  The authors found no change in TT, but a significant decline in free Testosterone.  This fits with other research pointing to free Testosterone as a better functional assessment tool.
Nathan Goodyear

Testosterone deficiency: A determinant of ao... [Atherosclerosis. 2014] - PubMed - NCBI - 0 views

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    low Total Testosterone associated with CAD, particularly aortic.  Obviously, Testosterone, when low, is a marker of poor health in men.  However, low Testosterone can likely play a role in disease development, especially when age is factored in--low Testosterone in younger men likely plays an etiology versus a lesser impact in the elder.
Nathan Goodyear

Testosterone Levels and Sexual Function Disorders ... [J Sex Med. 2013] - PubMed - NCBI - 0 views

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    Interesting finding in this study. They looked at Total Testosterone and bioavailable Testosterone and found that antidepressant therapy increased both values post treatment.  This is counter to what has been readably seen in men--with a decline.  The abstract here does not point disclose the actual Testosterone numbers.  I wonder if the well known disruption of the CYP enzymes by antidepressants slowed clearance and increased Testosterone levels.  This study did not look at other hormones or inflammatory cytokines.  Very tunneled vision study.  Nothing can be drawn from this study.
Nathan Goodyear

Relationship between Low Free Testosterone Levels and Loss of Muscle Mass : Scientific ... - 0 views

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    Study finds low free Testosterone and low calculated free Testosterone was associated with sarcopenia in Japanese men.  This association was not found with Total Testosterone.
Nathan Goodyear

Interrelationships of serum testosterone and free testosterone index with FFM and stren... - 0 views

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    Free Testosterone is better indicator of muscle strength than total Testosterone--in this case, free Testosterone index.
Nathan Goodyear

Evidence of male hypogonadism at an early age as a familial risk of type 2 diabetes. - ... - 0 views

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    male children of parents with diabetes found to have significantly lower serum total Testosterone, free Testosterone, and bioavailable Testosterone compared to male children of parents without diabetes.
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