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Nathan Goodyear

Testosterone level and mortality in elderly men with systolic chronic heart failure - 0 views

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    Good article.  Heart failure in men associated with lower Total Testosterone and estimated Free Testosterone. The severity of disease was associated with lower Testosterone levels.   I wish they would have measured free levels not estimated them.   Increased SHBG concentrations was associated increased CHF as well. This study found no association with mortality.
Nathan Goodyear

The association between hyperandrogenemia and the metabolic syndrome in morbidly obese ... - 0 views

  • a significant inverse relationship between HA and HDL-cholesterol levels which is in accordance with previous studies of women with PCOS
  • HA was associated with 61 % increased adjusted odds of MetS, and that this association was mainly driven by increased odds of dysglycemia and dyslipidemia
  • the prevalences of MetS, PCOS and HA were high among morbidly obese women <50 years of age
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  • Compared to women without HA, those with HA had significantly higher odds of having the MetS, which was mainly explained by the associations between HA and the lipid- and glucose components of the MetS
  • FTI-blood test might add value to the cardiovascular risk assessment of premenopausal women with morbid obesity
  • We calculated the free testosterone index (FTI) using the formula: FTI = 100 x serum testosterone (nmol/L) / sex hormone binding globulin (SHBG, nmol/L)
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    Another study that finds hyperandrogenism in women is associated with increased Metabolic Syndrome.  This study found obesity was associated with increased hyperandrogegism and Metabolic Syndrome irregardless of PCOS diagnosis or not.
Nathan Goodyear

Estrogen Metabolism and Risk of Breast Cancer in Postmenopausal Women - 0 views

  • The ratio of the 2-hydroxylation pathway to parent estrogens was associated with a statistically significantly decreased risk of breast cancer
  • In this study, this ratio was more strongly associated with the risk of breast cancer compared with the ratio of 2-hydroxylation pathway to 16-hydroxylation pathway or unconjugated estradiol alone
  • 2-hydroxylation pathway catechols have relatively low affinities for estrogen receptors (4) and are rapidly cleared from circulation
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  • In this study, the ratio of the 2-hydroxylation pathway to the 16-hydroxylation pathway was associated with a non-statistically significantly decreased risk of breast cancer
  • In this study, the ratio of catechols to methylated catechols in the 4-hydroxylation pathway was associated with statistically significantly increased risk of breast cancer.
  • This result is consistent with the hypothesis that mutagenic quinones derived from 4-hydroxylation pathway catechols contribute to pathogenesis of postmenopausal breast cancer.
  • Catechols in both the 2- and 4-hydroxylation pathways can be oxidized to form quinones; these reactive electrophiles can then react with DNA to form a variety of adducts
  • Methylation of the catechols prevents their conversion to reactive quinones
  • the most common DNA adducts derived from 4-hydroxylation pathway catechols are depurinating and highly mutagenic (7,40), most of those derived from 2-hydroxylation pathway catechols are stable and can be repaired with little error
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    Lower 2-OH estrone metabolism associated with lower risk of breast cancer, but 4-OH estrone associated with increased risk of breast cancer.
Nathan Goodyear

Salivary Testosterone and a Trinucleotide (CAG) Length Polymorphism in the Androgen Rec... - 0 views

  • Testosterone correlated inversely with participant age (r = −0.39, p = 0.012) and positively with number of CAG repeats
  • transactivation potential of the AR appears to decline in graded relation to an increasing number of CAG repeats, which are distributed over a normative range of 11–37 and, in Caucasian populations, commonly average 21–22 repeats
  • When activated by androgens, ARs translocate to the cell nucleus, where they exert transcriptional control of androgen-dependent genes by binding to androgen response elements within gene regulatory sequences
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  • androgens (like other steroid hormones) promote or repress the expression of genes specifying an array of cellular proteins
  • some evidence suggests a high number of CAG repeats may be associated with cognitive aging
  • diurnal variation in testosterone levels
  • salivary testosterone correlated negatively with participant age and positively with CAG length variation in the AR gene
  • CAG repeat number varied inversely with reactivity of the ventral amygdala to facial expressions of negative affect
  • higher salivary testosterone was likewise associated with a greater number of AR CAG repeats
  • relative androgen insensitivity in ARs with a larger number of CAG repeats
  • Because circulating testosterone is regulated via negative feedback through the hypothalamic-pituitary-gonadal axis, diminished androgen sensitivity at higher CAG repeat lengths may reduce feedback suppression of luteinizing hormone (LH). LH would then be maintained at higher levels, in turn promoting higher testosterone production
  • Testosterone up-regulates AVP expression in the amygdala
  • Oxytocin exerts an inhibitory influence on AVP expression in the central amygdala, and the synthesis of oxytocin is mediated by estrogen and estrogen receptors
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    Study used saliva to measure Testosterone levels in men.  Testosterone levels were inversely associated with age, but positively associated with CAG repeat sequences in the AR.
Nathan Goodyear

The relationship between testosterone, metabolic syndrome, and mean carotid intima-medi... - 0 views

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    Low Testosterone is associated with increased IMT.  Low T is associated with Mets.  MetS is associated with low T.  MetS is associated with increased IMT.
Nathan Goodyear

High Progesterone Receptor Expression in Prostate Cancer Is Associated with Clinical Fa... - 0 views

  • Currently, there is a general agreement of PGR presence in the stromal cells of PCa
  • expressed in both stromal and tumor cells of the PCa tissue
  • In univariate analysis, a high density level of PGR in both TE and TS was associated with CF
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  • High density level of PGR in the TE was an independent prognostic factor for CF.
  • Our large-sized study demonstrates a wide distribution of PGR in stromal and epithelial cells of both benign and malignant prostate tissue
  • there seems to be a general agreement of PGR presence in the stromal cells of PCa
  • In line with our findings, several have also reported a high PGR expression in TE of PCa [9,10,23,25]. In contrast, others have demonstrated a total lack of PGR expression in TE
  • the actions of progesterone are tissue specific
  • In our work univariate analysis demonstrated a high PGR expression in TS to be associated with clinical failure in PCa patients. So far we have not yet demonstrated the mechanism underlying this association
  • Several non-genomic proliferative actions of progesterone have been proposed in tumor cells of other organs, including breast [35–37], astrocytoma [38] and osteosarcoma [39] cell lines. However, such results are contradicted by suggestions of anti-proliferative actions of progesterone in endometrial cancer
  • Yu et al. found PGR to be negatively regulating stromal cell proliferation in vitro
  • high PGR density level in TE was associated with CF in patients with Gleason score ≥ 7
  • Bonkhoff et al. have suggested progressive emergence of PGR during PCa progression and metastasis
  • Latil and co-workers found a decreased PGR expression in clinically localized tumors and increased PGR expression in hormone-refractory tumors, when compared with normal prostate tissue
  • Our findings provide further support to these findings, indicating that PGR plays a role in the pathogenesis of PCa
  • Ki67 and PGR in TE were correlated with CF (S3 Text), indicating an association between PGR and proliferative activity
  • The mechanism behind the PGR up-regulation in PCa has not yet been elucidated
  • The PGR is, like the glucocorticoid receptor, similar to androgen receptor with 88% sequence homology in the ligand-binding domain
  • progesterone induced expression of androgen receptor-regulated genes could be a potential mechanism contributing to the development of castrate resistant PCa
  • A possibility of different roles by the two PGR isoforms in normal prostate tissue and PCa, as is suggested for the estrogen receptors [13], must also be taken into account
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    STudy finds that increased Progesterone receptor expression on epithelial and stromal cells is associated with increased clinical failure of therapy.  Several proposed mechanisms: 88% homologous with androgen receptor suggesting cross-stimulation and via progesterone induced increased androgen receptor gene stimulation i.e. epigenetics.
Nathan Goodyear

PLOS ONE: Increased Risk of Non-Fatal Myocardial Infarction Following Testosterone Ther... - 0 views

  • For all TT prescription subjects combined, the post/pre prescription rate ratio for MI (RR)was 1.36
  • In men aged 65 years and older the RR was 2.19 (1.27, 3.77), while in men under age 65 years the RR was 1.17
  • increasing RR with increasing age.
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  • The RRs were 0.95 (0.54, 1.67) under 55 years
  • 1.35 (0.77, 2.38) at 55–59
  • 1.29 (0.71, 2.35) at 60–64,
  • 1.35 (0.44, 4.18) at 65–69, 1.62
  • 3.43 (1.54, 7.66) at 75 years and older
  • The adjusted post/pre RR for PDE5I across all ages was 1.08
  • For TT prescription, in men under age 65 years, the RR was 2.90 (1.49, 5.62) for those with a history of heart disease and 0.90 (0.61, 1.34) for those without
  • In men aged 65 year and older, the RR was 2.16 (0.92, 5.10) for those with a history of heart disease and 2.21 (1.09, 4.45) for those without.
  • Among men aged 65 years and older, we observed a two-fold increase in the risk of MI in the 90 days after filling an initial TT prescription
  • Among younger men with a history of heart disease, we observed a two to three-fold increased risk of MI in the 90 days following an initial TT prescription and no excess risk in younger men without such a history
  • Among older men, the two-fold increased risk was associated with TT prescription regardless of cardiovascular disease history
  • our own findings appear consistent with a higher frequency of thrombotic events following TT prescription among men with more extensive coronary vascular disease.
  • Our findings are consistent with a recent meta-analysis of placebo-controlled randomized trials of testosterone therapy lasting 12 or more weeks among mainly older men, which reported that testosterone therapy increased the risk of adverse cardiovascular-related events (OR = 1.54, 95%CI:1.09, 2.18), as well as serious adverse cardiovascular-related events (OR = 1.61, 95%CI:1.01, 2.56) which included myocardial infarction along with other conditions
  • This association appeared unrelated to average baseline testosterone level (p = 0.70) but varied by source of funding (p = 0.03), with a stronger summary effect in a meta-analysis of studies not funded by the pharmaceutical industry (OR = 2.06, 95%CI:1.34, 3.17) compared with studies funded by the pharmaceutical industry
    • Nathan Goodyear
       
      This supports prior analysis that studies done by pharmaceutical corps will be more favorable to their product(s) than those independently funded.  This is called bias.
  • the evidence supports an association between testosterone therapy and risk of serious, adverse cardiovascular-related events–including non-fatal myocardial infarction–in men
  • there is some evidence that low endogenous testosterone levels may also be positively associated with cardiovascular events
  • effects of endogenous and exogenous testosterone may differ. Exogenous testosterone (TT) is associated with physiologic changes that predispose to clotting and thrombotic disorders including increased blood pressure [18], polycythemia [19], reductions in HDL cholesterol [18], [20], and hyperviscosity of the blood and platelet aggregation. [20]–[23]; TT also increases circulating estrogens [24], [25] which may play a role in the observed excess of adverse cardiovascular-related events, given that estrogen therapy has been associated with this excess in both men and women
  • did not include information on the serologic or diagnostic indications for treatment.
  • no association between PDE5I prescriptions and the risk of MI
  • Recently TT has been increasing extraordinarily rapidly, including among younger men and among those without hormone measurement
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    New cohort study finds increased risk of Testosterone in men > 65 and those : these are based in marketing-based medicine not evidence based medicine.
Nathan Goodyear

Lower-But-Normal Serum TSH level Is Associated With the Development or Progression of C... - 0 views

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    This study points to an association between a low-normal TSH and cognitive decline in the elderly.  An association is not causative, but functional hypothyroidism does result in cognitive impairment, so the association would logically fit.  The results of this study do as well.
Nathan Goodyear

Association between serum testosterone... [Neuro Endocrinol Lett. 2014] - PubMed - NCBI - 0 views

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    Study finds that higher BMI and insulin levels associated with decline Testosterone levels.  But, so were risperidone and olanzapine in schizophrenic patients.  The association between the medications and the BMI and insulin was less in the meds, but still present.  The risperidone had a greater association with a lower Testosterone.  Increasing estradiol levels correlated with the low Testosterone levels.
Nathan Goodyear

Low testosterone levels are associated with metabolic syndrome, in elderly men: the rol... - 0 views

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    Low Serum Testosterone inversely associated metabolic syndrome in men.  This study was conducted in the Ikaria islands.  No association was found with women and Testosterone.  In men, Testosterone was inversely associated with waist circumference, hs-CRP, insulin, and HDL.
Nathan Goodyear

Association of metabolic syndrome ... [Indian J Endocrinol Metab. 2014] - PubMed - NCBI - 0 views

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    Metabolic Syndrome is associated with CAD.  No surprise here, but increase in # of metabolic syndrome parameters was associated with increasing % of Triple vessel disease.   No surprise that MetS was associated with TNF-alpha, IL-6, IR, and hsCRP.
Nathan Goodyear

Urinary Estrogens and Estrogen Metabolites and Subsequent Risk of Breast Cancer among P... - 0 views

  • both 2- and 4-catechol estrogen metabolites bind to the ER with affinities comparable with estradiol, 4-catechol estrogen metabolites have lower dissociation rates than estradiol and an enhanced ability to upregulate ER-dependent processes
  • 2-catechol estrogen metabolites act as either weak mitogens (39) or weak inhibitors of cell proliferation
  • While 16α-hydroxyestrone binds to the ER with lower affinity than estradiol, it binds covalently (41) and leads to a constitutively activated ER
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  • 4-hydroxyestradiol and 16α-hydroxyestrone increasing proliferation and decreasing apoptosis in a manner similar to estradiol; however, these effects were achieved only at concentrations 10-fold higher than estradiol (39). In contrast, 2-hydroxyestradiol did not have substantial proliferative or antiapoptotic effects
  • In our study, the associations with both 2-hydroxyestrone and 16α-hydroxyestrone were nonsignificantly inverse and we did not observe a consistent trend or significant associations between the 2-hydroxyestrone:16α-hydroxyestrone ratio and breast cancer risk
  • Ratios of the 3 hydroxylation pathways were not significantly associated with risk although the 2:16-pathway and 4:16-pathway ratios were suggestively inversely associated
  • a significant inverse association with the ratio of parent estrogens to estrogen metabolites
  • several potentially estrogenic and genotoxic mechanisms
  • Estrogen metabolites also can be genotoxic
  • Catechol estrogens can be oxidized into quinones and induce DNA damage directly through the formation of DNA adducts, or indirectly via redox cycling and generation of reactive oxygen species
  • the oxidized forms of the catechol estrogens differ in their ability to damage DNA through adducts, with oxidized 2-catechols forming stable and reversible DNA adducts and oxidized 4-catechols forming unstable adducts, which lead to depurination and mutations
  • 2- and 4-catechols have been shown to produce reactive oxygen species and induce oxidative DNA damage
  • act independently from the ER
  • 16α-Hydroxyestrone also may be genotoxic
  • While the catechol estrogens have estrogenic and genotoxic potential, the methylated catechol estrogens, which are catechol estrogens with one hydroxyl group methylated, have been hypothesized to lower the risk of breast cancer
  • The suggested mechanisms are indirect, by decreasing circulating levels of catechol estrogens and thereby the opportunity for catechols to exert genotoxic or proliferative effects, or direct, by inhibiting tumor growth and inducing apoptosis
  • the balance between phase I (oxidation) and phase II (methylation) metabolism of estrogen may be important in hormonally related cancer development.
  • Despite the estrogenic and genotoxic potential of many of the estrogen metabolites, we only observed a significantly increased breast cancer risk with one estrogen metabolite, 17-epiestriol, which has particularly strong estrogenic activity and binds to both ERα and ERβ with an affinity comparable with estradiol
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    review of estrogen metabolites and breast cancer risk in premenopausal women.
Nathan Goodyear

The Association between Premature Coronary Art... [Arch Iran Med. 2014] - PubMed - NCBI - 0 views

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    Low free and Total Testosterone levels found to be associated with premature CAD in men.  Some confounders were present, which they tried to account for--this should leave some healthy questioning of this study results.  That being said, this is not the first time low T has been found to be associated with CAD in men.  This study found a statistical significant association with Free and Total Testosterone levels in young men.  Another point to consider is the Low T a cause or a biomarker and an effect of poor/declining health?  I would so more to the biomarker point.
Nathan Goodyear

Associations between sex hormone binding globulin and metabolic syndrome parameters in ... - 0 views

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    Low SHGB associated with increased association with metabolic syndrome components.  Low SHBG particuraliy associated with increased obesity (visceral) and glucose dysmetabolism. This study looked at premenopausal women.
Nathan Goodyear

Inverse association between serum insulin and sex hormone-binding globulin in a populat... - 0 views

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    Low SHBG associated with elevated insulin levels. This was found in both sexes.  Low SHBG associated with type II Diabetes, but Increased SHBG found to be associated with Type I Diabetes.
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

Associations between cadmium exposure and circulating levels of sex... - PubMed - NCBI - 0 views

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    Cadmium levels found to be positively associated with serum Testosterone levels in women.  Cadmium inversely associated with E2 levels.  Cadmium has been associated with increased breast cancer risk in women.
Nathan Goodyear

Association Between Endogenous Sex Hormones and Liver Fat in a Mult... - PubMed - NCBI - 0 views

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    Time that physicians start following the science.  Study using data from the Multi-ethnic Study of Atherosclerosis was used to assess hormones and fatty liver in men and women.  Increasing bioavailable Testosterone levels in women was found to be associated with increasing fatty liver in post-menopausal women.  The opposite was found to be true in men.  Higher Estradiol levels were found to be associated with increased fatty liver in both sexes.  However, the statistical significance was higher with men.  Higher SHBG was associated with lower fatty liver incidence in men.  
Nathan Goodyear

Association of Mean Platelet Volume With Androgens and Insulin Resistance in Nonobese P... - 0 views

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    Mean Platelet Volume (MPV) is associated with increased cardiovascular disease in some studies.  Hyperandrogenism is associated with increased CVD in women with PCOS. This study found that elevated androgen levels in non obese women with/without PCOS was associated with lower MPV values.  This stands in contrast to other studies. 
Nathan Goodyear

Association of serum lead and mercury level with cardiometabolic ri... - PubMed - NCBI - 0 views

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    study finds Pb and Hg associated with increased cardiometabolic risk factors.  Elevated liver enzymes found to be positively associated with serum Pb levels.  Metabolic Syndrome was found to be associated with higher Pb and Hg levels.
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