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Nathan Goodyear

Chemistry and Structural Biology of Androgen Receptor - 0 views

www.ncbi.nlm.nih.gov/...PMC2096617

androgens Testosterone DHT dihydrotestosterone AR androgen receptors male hormones hormones

shared by Nathan Goodyear on 28 Sep 16 - No Cached
  • Healthy adult men typically produce approximately 3–10 mg of testosterone per day
  • circulating levels ranging from 300 to 700 ng/dL in eugonadal men
  • endogenous testosterone secretion is pulsatile and diurnal
  • ...15 more annotations...
  • highest concentration occurring at about 8:00 a.m. and the lowest at about 8:00 p.m.
  • Average serum concentrations and diurnal variation in testosterone diminish as men age
  • 40% is sequestered with high affinity to sex hormone-binding globulin (SHBG)
  • almost 60% is bound with low affinity to albumin
  • 2% as free, unbound hormone
  • 5α-DHT has even greater binding affinity to sex hormone-binding globulin than does testosterone
  • 5α-DHT is only about 5% as abundant in the blood as testosterone and is largely derived from peripheral metabolism of testosterone
  • Both 5α-reduction and aromatization are irreversible processes
  • Approximately 90% of an oral dose of testosterone is metabolized before it reaches the systemic circulation
  • there are three modes of action of testosterone. It may directly act through AR in target tissues where 5α-reductase is not expressed, be converted to 5α-DHT (5–10%) by 5α-reductase before binding to AR, or be aromatized to estrogen (0.2%) and act through the estrogen receptor
  • 5α-DHT is a more potent AR ligand than testosterone
  • has 2–10-fold higher potency than testosterone in androgen-responsive tissues
  • estrogen plays a major role in regulating metabolic process,74,75 mood and cognition,76 cardiovascular disease,77,78 sexual function including libido,79 and bone turnover in men
  • Free testosterone is considered the most “biologically active” form
  • testosterone is the major androgen that acts in the “DHT-independent” tissues, such as skeletal muscle, where 5α-reductase is not expressed or is expressed at a very low level
  • Nathan Goodyear on 28 Sep 16
     
    good review of androgens and AR.
Nathan Goodyear

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

www.townsendletter.com/...metsyndrome0712.html

testosterone male men hormone hormones saliva salivary low T low metabolic syndrome MetS

shared by Nathan Goodyear on 28 Aug 12 - No Cached
  • 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
  • ...11 more annotations...
  • 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
  • Nathan Goodyear on 28 Aug 12
     
    nice and short review on testosterone and men's  health.
Nathan Goodyear

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

press.endocrine.org/...jc.2014-1872

low T Testosterone treatment therapy diabetes obesity men male hormone hormones

shared by Nathan Goodyear on 29 Jul 14 - No Cached
  • Nathan Goodyear on 29 Jul 14
     
    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

Low Free Testosterone Is Associated with Hypogonadal Signs and Symptoms in Men with Normal Total Testosterone: The Journal of Clinical Endocrinology & Metabolism: Vol 101, No 7 - 0 views

press.endocrine.org/...jc.2015-4106

low T low testosterone Testosterone free Testosterone male hormones hormones men

shared by Nathan Goodyear on 19 Sep 16 - No Cached
  • Nathan Goodyear on 19 Sep 16
     
    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

[Bone and Men's Health. Measurement of salivary te... [Clin Calcium. 2010] - PubMed result - 0 views

www.ncbi.nlm.nih.gov/...20118513

saliva salivary testosterone biodentical testng

shared by Nathan Goodyear on 22 Nov 10 - No Cached
  • Testosterone is secreted into saliva. In saliva, testosterone is not bound to proteins. Thus concentration of testosterone in saliva is quite close to the serum free testosterone level. Currently serum free testosterone is measured by a convenient method in Japan, that reflects only 10% of the correct values. However, the correct measurement of serum free testosterone is quite costly. Collection of saliva is not invasive to subjects, and it can be done without paramedicals. Besides it is relatively cheaper. Acquisition of samples in multiple occasions is possible. These advantages of utilizing saliva will introduce the measurements of salivary testosterone in cohort studies or screening of low testosterone levels in the community.
  • Nathan Goodyear on 22 Nov 10
     
    Saliva Testing of Testosterone is standard
Nathan Goodyear

Secular Decline in Male Testosterone and Sex Hormone Binding Globulin Serum Levels in Danish Population Surveys - 0 views

jcem.endojournals.org/...4696.long

decline male testosterone hormone danish low t low Testosterone men SHBG serum levels

shared by Nathan Goodyear on 10 Dec 12 - No Cached
  • Serum SHBG levels are negatively associated with obesity and various measures of insulin resistance
  • SHBG levels increase during pharmacological oral estrogen treatment
  • insulin decreases SHBG productio
  • ...5 more annotations...
  • The secular decline in SHBG and testosterone serum levels did not lead to a change in the level of free testosterone
  • existence of specific binding sites for SHBG at the cell membrane of steroid-responsive tissues has been shown
  • it is alarming that changes of this magnitude can be detected over such a relatively short time
  • Sex steroids stimulate SHBG production and secretion in vitro
  • Serum testosterone levels decreased and SHBG levels increased with increasing age
  • Nathan Goodyear on 10 Dec 12
     
    lower levels of SHBG and serum testosterone were found in more recently born men.  Preceding generations of men produced higher testosterone levels than men born in more recent generations.
Nathan Goodyear

The prevalence of hypogonadism in diabetic men in Isfahan Endocrine and Metabolism Research Center, Isfahan, Iran - 0 views

www.ncbi.nlm.nih.gov/...PMC3685773

low T low Testosterone Diabetes men Iran low testosterone T hormone hormones

shared by Nathan Goodyear on 02 Jul 13 - No Cached
  • Nathan Goodyear on 02 Jul 13
     
    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

Effect of Tongkat Ali on stress hormones and psychological mood state in moderately stressed subjects - 0 views

www.ncbi.nlm.nih.gov/...PMC3669033

Tongkat Ali long jack cortisol stress testosterone hormone hormones

shared by Nathan Goodyear on 09 Mar 15 - No Cached
  • At the age of 60, testosterone levels are typically only 40-50% of youthful levels and may be lower
  • Eurycoma contains a group of small peptides referred to as “eurypeptides” that are known to have effects in improving energy status and sex drive in studies of rodents
  • The effects of tongkat ali in restoring normal testosterone levels appears to be less due to actually “stimulating” testosterone synthesis, but rather by increasing the release rate of “free” testosterone from its binding hormone, sex-hormone-binding-globulin (SHBG)
  • ...6 more annotations...
  • The current study found that daily supplementation with tongkat ali root extract (200 mg/day) improves stress hormone profile (lower cortisol; higher testosterone) and certain mood state parameters (lower tension, anger, and confusion)
  • tongkat ali supplementation (100 mg/day) improved lean body mass, 1-RM strength, and arm circumference to a significantly greater degree compared to a placebo group.
  • In a recent 12-week trial [46] of Eurycoma longifolia supplementation (300 mg/day), men (30–55 years of age) showed significant improved compared to placebo in the Physical Functioning domain of the SF-36 quality of life survey
  • sexual libido was increased by 11%
  • In men with low testosterone levels (average age 51 years), one month of daily supplementation with tongkat ali extract (200 mg/day) resulted in a significant improvement in serum testosterone levels and quality-of-life parameters
  • rise in cortisol and drop in testosterone is an early signal of “overtraining”
  • Nathan Goodyear on 09 Mar 15
     
    Tongkat Ali, commonly known as long jack, is found to reduce stress and increase Testosterone.  Stress is one of the common causes of low T in men.  It appears that long Jack functions as an adaptogen.
Nathan Goodyear

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

www.ncbi.nlm.nih.gov/...24867133

men male hormone hormones BMD free Testosterone Total low T

shared by Nathan Goodyear on 03 Jun 14 - No Cached
  • Nathan Goodyear on 03 Jun 14
     
    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

Morning free and total testosterone in HIV-infected men: implications for the assessment of hypogonadism - 0 views

www.ncbi.nlm.nih.gov/...PMC3900935

free Testosterone HIV men hormone hormones male SHBG

shared by Nathan Goodyear on 03 Feb 14 - No Cached
  • Nathan Goodyear on 03 Feb 14
     
    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

Relationship between Low Free Testosterone Levels and Loss of Muscle Mass : Scientific Reports : Nature Publishing Group - 0 views

www.nature.com/...srep01818.html

low T Testosterone low T low Testosterone free Testosterone sarcopenia muscle mass men male hormone hormones

shared by Nathan Goodyear on 13 Aug 14 - No Cached
  • Nathan Goodyear on 13 Aug 14
     
    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 strength in aging men | Endocrinology and Metabolism - 0 views

ajpendo.physiology.org/...E284.long

free Testosterone Testosterone muscle hormone hormones strength aging

shared by Nathan Goodyear on 05 Apr 15 - No Cached
  • Nathan Goodyear on 05 Apr 15
     
    Free Testosterone is better indicator of muscle strength than total Testosterone--in this case, free Testosterone index.
Nathan Goodyear

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

www.ncbi.nlm.nih.gov/...21854402

low T Testosterone diabetes obesity age men male hormone hormones free Testosterone total Testosterone ED QOl

shared by Nathan Goodyear on 29 Jul 14 - No Cached
  • Nathan Goodyear on 29 Jul 14
     
    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

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

www.ncbi.nlm.nih.gov/...26639184

Diabetes low Testosterone hormones male hormones low T Testosterone free Testosterone bioavailable Testosterone

shared by Nathan Goodyear on 21 Dec 15 - No Cached
  • Nathan Goodyear on 21 Dec 15
     
    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.
Nathan Goodyear

Testosterone Treatment and Sexual Function in Older Men with Low Testosterone Levels: The Journal of Clinical Endocrinology & Metabolism: Vol 0, No 0 - 0 views

press.endocrine.org/...jc.2016-1645

low T low Testosterone Testosterone male hormones libido ED estradiol hormones

shared by Nathan Goodyear on 13 Jul 16 - No Cached
  • Nathan Goodyear on 13 Jul 16
     
    new study finds that men >65 with low libido and Testosterone levels < 275 increase sexual function with Testosterone therapy.  Only libido was improved; no benefit to erectile function was noted--note that is likely due to depleted NO.  Given time that should improve with he increase in NO synthase and thus NO.  I have a fault with on elf the comments on this study: they point out that increased free Testosterone and estradiol levels were associated with improved sexual activity.  This lacks an understanding of the physiology.  In men with low T > 65, the majority are dealing with inflammation and excess weight; all of which increase aromatase activity and thus estradiol activity.  This does not indicate that an increase in estradiol activity is associated with improved libido in men.  How can elevated estrogen levels lead to low T and then increase levels are associated with improved libido?  This is merely a reflection of the body's dysfunctional physiology.  This observation of increased estradiol by no means shows cause and effect.  Scientists need to due a better job in vetting what they write!
Nathan Goodyear

Ibuprofen alters human testicular physiology to produce a state of compensated hypogonadism - 0 views

www.pnas.org/...1715035115.full

ibuprofen Testosterone epigenetics hormones low Testosterone low T

shared by Nathan Goodyear on 09 Jan 18 - No Cached
  • The levels of LH in the ibuprofen group had increased by 23% after 14 d of administration
  • This increase was even more pronounced at 44 d, at 33%
  • We found an 18% decrease (P = 0.056) in the ibuprofen group compared with the placebo group after 14 d (Fig. 1A) and a 23% decrease (P = 0.02) after 44 d (Fig. 1C). Taken together, these in vivo data suggest that ibuprofen induced a state of compensated hypogonadism during the trial, which occurred as early as 14 d and was maintained until the end of the trial at 44 d
  • ...27 more annotations...
  • We first investigated testosterone production after 24 and 48 h of ibuprofen exposure to assess its effects on Leydig cell steroidogenesis. Inhibition of testosterone levels was significant and dose-dependent (β = −0.405, P = 0.01 at 24 h and β = −0.664, P &lt; 0.0001 at 48 h) (Fig. 2A) and was augmented over time
  • The AMH data show that the hypogonadism affected not only Leydig cells but also Sertoli cells and also occurred as early as 14 d of administration
  • Sertoli cell activity showed that AMH levels decreased significantly with ibuprofen administration, by 9% (P = 0.02) after 14 d (Fig. 1B) and by 7% (P = 0.05) after 44 d compared with the placebo group
  • Examination of the effect of ibuprofen exposure on both the ∆4 and ∆5 steroid pathways (Fig. 2B) showed that it generally inhibited all steroids from pregnenolone down to testosterone and 17β-estradiol; the production of each steroid measured decreased at doses of 10−5–10−4 M. Under control conditions, production of androstenediol and dehydroepiandrosterone (DHEA) was below the limit of detection except in one experiment with DHEA
  • Measuring the mRNA expression of genes involved in steroidogenesis in vitro showed that ibuprofen had a profound inhibitory effect on the expression of these genes (Fig. 3 B–D), consistent with that seen above in our ex vivo organ model. Taken together, these data examining effects on the endocrine cells confirm that ibuprofen-induced changes in the transcriptional machinery were the likely reason for the inhibition of steroidogenesis.
  • Suppression of gene expression concerned the initial conversion of cholesterol to the final testosterone synthesis. Hence, expression of genes involved in cholesterol transport to the Leydig cell mitochondria was impaired
  • A previous study reported androsterone levels decreased by 63% among men receiving 400 mg of ibuprofen every 6 h for 4 wk
  • We next examined the gene expression involved in testicular steroidogenesis ex vivo and found that levels of expression of every gene that we studied except CYP19A1 decreased after exposure for 48 h compared with controls
  • the changes in gene expression indicate that the transcriptional machinery behind the endocrine action of Leydig cells was most likely impaired by ibuprofen exposure.
  • Together, these data show that ibuprofen also directly impairs Sertoli cell function ex vivo by inhibiting transcription
  • ibuprofen use in men led to (i) elevation of LH; (ii) a decreased testosterone/LH ratio and, to a lesser degree, a decreased inhibin B/FSH ratio; and (iii) a reduction in the levels of the Sertoli cell hormone AMH
  • The decrease in the free testosterone/LH ratio resulted primarily from the increased LH levels, revealing that testicular responsiveness to gonadotropins likely declined during the ibuprofen exposure. Our data from the ex vivo experiments support this notion, indicating that the observed elevation in LH resulted from ibuprofen’s direct antiandrogenic action
  • AMH levels were consistently suppressed by ibuprofen both in vivo and ex vivo, indicating that this hormone is uncoupled from gonadotropins in adult men. The ibuprofen suppression of AMH further demonstrated that the analgesic targeted not only the Leydig cells but also the Sertoli cells, a feature encountered not only in the human adult testis but also in the fetal testis
  • ibuprofen displayed broad transcription-repression abilities involving steroidogenesis, peptide hormones, and prostaglandin synthesis
  • a chemical compound, through its effects on the signaling compounds, can result in changes in the testis at gene level, resulting in perturbations at higher physiological levels in the adult human
  • The analgesics acetaminophen/paracetamol and ibuprofen have previously been shown to inhibit the postexercise response in muscles by repressing transcription
  • Previous ex vivo studies on adult testis have indeed pointed to an antiandrogenicity, only on Leydig cells, of phthalates (41), aspirin, indomethacin (42), and bisphenol A (BPA) and its analogs
  • ibuprofen’s effects were not restricted to Leydig and Sertoli cells, as data showed that the expression of genes in peritubular cells was also affected
  • short-term exposure
  • In the clinical setting, compromised Leydig cell function resulting in increased insensitivity to LH is defined as compensated hypogonadism (4), an entity associated with all-cause mortality
  • compensated hypogonadic men present with an increased likelihood of reproductive, cognitive, and physical symptoms
  • an inverse relationship was recently reported between endurance exercise training and male sexual libido
  • AMH concentrations are lower in seminal plasma from patients with azoospermia than from men with normal sperm levels
  • inhibin B is a key clinical marker of reproductive health (32). The function of AMH, also secreted by Sertoli cells, and its regulation through FSH remain unclear in men
  • the striking dual effect of ibuprofen observed here on both Leydig and Sertoli cells makes this NSAID the chemical compound, of all the chemical classes considered, with the broadest endocrine-disturbing properties identified so far in men.
  • after administration of 600 mg of ibuprofen to healthy volunteers
  • 14 d or at the last day of administration at 44 d
  • Nathan Goodyear on 09 Jan 18
     
    ibuprofen alters genetic expression that results in decreased Testosterone production.
Nathan Goodyear

Calculated free testosterone and radioimmunoassay free testosterone as a predictor of subnormal levels of total testosterone. - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...21997201

low T low Testosterone Testosterone male hormones men hormones

shared by Nathan Goodyear on 19 Sep 16 - No Cached
  • Nathan Goodyear on 19 Sep 16
     
    In this study, calculated low free Testosterone correlated better with TT than radioimmunoassay free Testosterone.
Nathan Goodyear

Association of Free Testosterone With Hypogonadal Symptoms in Men With Near-normal Total Testosterone Levels. - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...26199166

low T low Testosterone Testosterone free Testosterone male hormones men

shared by Nathan Goodyear on 11 Aug 15 - No Cached
  • Nathan Goodyear on 11 Aug 15
     
    only abstract available here, but the authors conclude that free Testosterone is no associated with low T symptoms with near normal serum TT.  Not so fast, the study did find that free Testosterone did prove significant in younger men and this is exactly when the TT and fT appear to have significant discrepencies.
Nathan Goodyear

Endogenous Steroid Hormone Concentrations and Risk of Breast Cancer Among Premenopausal Women - 0 views

jnci.oxfordjournals.org/...1406.long

hormone hormones Testosterone free total estradiol breast cancer women female

shared by Nathan Goodyear on 21 Mar 14 - No Cached
  • Nathan Goodyear on 21 Mar 14
     
    Prospective study finds that elevated total and free Estradiol levels in the follicular phase and elevated total and free Testosterone levels in both the follicular and luteal phase are associated with increased breast cancer in women.  The risk is for pre menopause in this study.  This and several other studies point to serious questions about the massive dosing of Testosterone via pellets, injections, and topicals for libido.  We appear to be following the same patter as seen with premarin, provera, now Testosterone in men and this may be the next ball to drop.  Is the Testosterone therapy merely producing an environment that feeds breast cancer?
Nathan Goodyear

The rs5934505 single nucleotide polymorphism (SNP) is associated with low testosterone and late-onset hypogonadism, but the rs10822184 SNP is assoc... - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...26602056

epigenetics low T low Testosterone Testosterone SNPs

shared by Nathan Goodyear on 19 Sep 17 - No Cached
  • Nathan Goodyear on 19 Sep 17
     
    Four SNPs, rs12150660, rs727428, rs5934505, and rs10822184 associated with late-onset hypogonadism (low T) and obesity in men of European descent.  In Chinese populations, rs5934505 was associated with increased risk of low Total Testosterone and calculated free Testosterone.  OR was 2.01 for low TT and 2.14 for low calculated free Testosterone.
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