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Nathan Goodyear

Circulating 2-hydroxy and 16-α hydroxy estrone levels and risk of breast canc... - 1 views

www.ncbi.nlm.nih.gov/...PMC2562592

estrogen metabolism menopause post-menopause post menopause estrogen metabolite 2-OH-estrone 16-alpha-OH-estrone 2:16alpha-OH estrone breast cancer risk hormone hormones

shared by Nathan Goodyear on 21 Aug 14 - No Cached
  • 2-OH estrogens bind to the estrogen receptor (ER) with affinity equivalent to or greater than estradiol
  • previous prospective studies have not observed any significant associations with either 2-OH or 16α-OH estrone or the ratio of the two metabolites and breast cancer risk overall.
    • Nathan Goodyear
      Nathan Goodyear on 08 Oct 15
       
      whether that risk is increased or decreased
  • it has been hypothesized that metabolism favoring the 2-OH over the 16α-OH pathway may be inversely associated with breast cancer risk (28).
  • ...24 more annotations...
  • they may act as only weak mitogens (14, 15), or as inhibitors of proliferation
  • No significant associations have been observed between 2-OH estrone and breast cancer risk
  • While 16α-OH estrone binds to the ER with lower affinity than estradiol, it binds covalently (18-20) and once bound, fails to down-regulate the receptor (21). Thus, 16α-OH estrone stimulates cell proliferation in a manner comparable to estradiol in ER+ breast cancer cell lines
  • In this large prospective study of 2-OH and 16α-OH estrone metabolites and breast cancer risk, we did not observe any significant associations overall with either individual metabolite or with the ratio of the two metabolites
  • we observed positive associations with 2-OH estrone and the 2:16α-OH estrone ratio among women with lower BMI and women with ER-/PR-tumors,
  • To date, several epidemiologic studies have examined the association between the 2-OH and 16α-OH estrogen metabolites and breast cancer risk with inconclusive results.
  • circulating estrogen levels have been associated more strongly with ER+/PR+ tumors than with ER-/PR- tumors
  • our results do not support the hypothesis that metabolism favoring the 2-OH estrone pathway is more beneficial to breast cancer risk than that favoring the 16α-OH estrone pathway
  • we observed significant positive associations of both 2-OH estrone and the 2:16α-OH estrone ratio with ER-/PR-tumors
  • Three (30, 32, 33) of four (30-33) studies observed RRs above 1 for the association between 16α-OH estrone and breast cancer risk (range of RRs=1.23-2.47); none of the point estimates was statistically significant though one trend was suggestive
  • based on animal studies, 2-OH estrone and the 2:16α-OH estrone ratio have been hypothesized to be inversely associated with breast cancer risk
  • No significant associations have been observed between 2-OH estrone, 16α-OH estrone, or the 2:16α-OH estrone ratio and breast cancer risk and the direction of the estimates is not consistent across studies.
    • Nathan Goodyear
      Nathan Goodyear on 08 Oct 15
       
      better worded is no consistent, significant associations.   There are some studies that point to the 16 catecholestrogen and increased cancer risk; limited studies show negative effects of 2 catecholestrogens on cancer risk and prospective studies available pretty much dispel the idea that the 2:16 ratio has an risk predictability.
  • we observed a suggestive inverse association with 16α-OH estrone and a significant positive association with the 2:16α-OH estrone ratio among lean women, suggesting possible associations in a low estrogen environment.
  • 16α-OH estrone increases unscheduled DNA synthesis in mouse mammary cells (27) and hence also may be genotoxic
  • Although 2-OH estrogens are capable of redox cycling, the semiquinones and quinones (i.e., the oxidized forms) form stable DNA adducts that are reversible without DNA destruction
  • In our population of PMH nonusers, we observed no associations with ER+/PR+ tumors, but significant positive associations with 2-OH estrone and the 2:16α-OH estrone ratio among women with ER-/PR- tumors
    • Nathan Goodyear
      Nathan Goodyear on 08 Oct 15
       
      one of the few studies to find this association between 2 catecholestrogens and the 2:16 ratio and ER-/PR-tumors
  • Animal and in vitro studies have shown that hydroxy estrogens can induce DNA damage either directly, through the formation of quinones and DNA adducts, or indirectly, through redox cycling and the generation of reactive oxygen species
    • Nathan Goodyear
      Nathan Goodyear on 08 Oct 15
       
      genotoxic via directe DNA adducts and indirectly via ROS; this is in addition to the proliferative effect
  • we observed a significant positive association between the 2:16α-OH estrone ratio and breast cancer risk among lean women
  • No significant associations have been observed with the 2:16α-OH estrone ratio
  • In the Danish study, no associations were observed with either ER+ or ER- tumors among PMH nonusers
  • significant positive associations with 2-OH estrone and the 2:16α-OH estrone ratio were observed among PMH users with ER+, but not ER-, tumors
  • it is possible that the genotoxicity of 2-OH estrone plays a role in hormone receptor negative tumors
  • 4-OH estrogens have a greater estrogenic potential than 2-OH estrogens, given the lower dissociation rate from estrogen receptors compared with estradiol (61), and are potentially more genotoxic since the quinones form unstable adducts, leading to depurination and mutation in vitro and in vivo
  • the balance between the catechol (i.e., 2-OH and 4-OH) and methoxy (i.e., 2-Me and 4-Me) estrogens may impact risk
  • Nathan Goodyear on 21 Aug 14
     
    The risks of estrogen metabolism are not clear cut.  Likely never will be due to the complexity of individual metabolism.  This study found no correlation between 2OH-Estrone and 2OH:16alpha-Estrone and breast cancer risk in ER+/PR+ breast cancer.  Translated: no benefit in breast cancer risk in 2OH-Estrone metabolism or increased 2OH:16alpha estrone metabolism.  There was a positive association between 2OH-Estrone and 2:16alpha-Estrone in women with ER-/PR- tumors and low BMI.
  • anonymous on 28 Oct 15
     
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Nathan Goodyear

Circulating Estrogen Metabolites and Risk for Breast Cancer in Premenopausal Women - 0 views

cebp.aacrjournals.org/...2273.short

estrogen metabolism estrogen metabolite estrogen metabolism breast cancer 2-OH-estrone 16alpha-OH-estrone estrone metabolite metabolites

shared by Nathan Goodyear on 21 Aug 14 - No Cached
  • Nathan Goodyear on 21 Aug 14
     
    Epidemiologic study finds no association between increased 2OH-estrone metabolism and increased 2OH:16alphaOH-estrone metabolism and a reduction in breast cancer risk.
Nathan Goodyear

Circulating Estrone Levels Are Associated Prospectively With Diabetes Risk in Men of th... - 0 views

care.diabetesjournals.org/...2591.full

low T Testosterone Estrone Estradiol type II diabetes Framingham heart study men male hormone hormones diabetes estrogen heart

shared by Nathan Goodyear on 13 May 14 - No Cached
  • Nathan Goodyear on 13 May 14
     
    A cross-sectional study of 1,458 men over a 13 years found an increase risk of diabetes incidence with elevated Estradiol and Estrone levels.  The greatest association was found with Estrone.  This should come as no surprise to anybody as type II diabetes is clearly associated with increasing weight and this is the source of 80% of estrogen production in men.
Nathan Goodyear

Circulating Estrogen Metabolites and Risk for Breast Cancer in Premenopausal Women - 0 views

www.ncbi.nlm.nih.gov/...PMC3000741

estrogen metabolites estrogen metabolism estrogen 2-OH-estrone 16-alpha-OH-estrone cancer breast cancer women

shared by Nathan Goodyear on 18 Sep 15 - No Cached
  • Nathan Goodyear on 18 Sep 15
     
    no statistical significant association between 2OH-estrone, 16-alpha-OH-estrone, and their ratio found to be associated with increased breast cancer risk in pre menopause women.
Nathan Goodyear

Estrogen metabolite ratio: is the 2-OH estrone to 16alph-OH estrone ratio predictive of... - 0 views

www.ncbi.nlm.nih.gov/...ijwh-3-037.pdf

estrogen metabolism cancer breast prostate metabolites 2-OH estrone 16alpha-OH

shared by Nathan Goodyear on 17 Feb 12 - No Cached
  • Nathan Goodyear on 17 Feb 12
     
    This is a recent review of the literature regarding estrogen metabolism. It has been proposed that 2:16 OH estrone ratio is predictive of breast, prostate cancer. This study does not find that association
Nathan Goodyear

Effect of aging on endogenous level of 5 alpha-dihydrotestosterone, testosterone, estra... - 0 views

jcem.endojournals.org/...375.short

BPH testosterone DHT Estradiol Estrone E2 E1 men prostate aging

shared by Nathan Goodyear on 18 Sep 12 - No Cached
  • Nathan Goodyear on 18 Sep 12
     
    Men with BPH found to have higher levels of stromal Estradiol and Estrone.  This is associated with aging.  This elevation was not found in the prostate epithelium.  No correlation with Testosterone and the stroma and epithelium were found.  So, the point is that what is happening in the prostate appears to be related to increased aromatase activity in the prostate.  Which this has been shown to be evident in the lateral lobes of the prostate in other studies.  But DHT?  The numbers here are slightly elevated.  BUt the balance of DHT to Estradiol may be more important than the individual levels.  This study was done in humans.
Nathan Goodyear

Abnormal levels of serum dehydroepiandrosterone, estrone, and estradiol in men with rhe... - 0 views

www.jrheum.org/...2338.short

estradiol inflammation estrone aromatase activity aromatization rheumatoid arthritis RA men

shared by Nathan Goodyear on 07 Mar 12 - No Cached
  • Nathan Goodyear on 07 Mar 12
     
    elevated estradiol associated with increased inflammation symptoms in men with RA. Not found with estrone.
Nathan Goodyear

Estrone sulfate (E1S), a prognosis marker for tumor aggressiveness in prostate cancer (... - 0 views

www.sciencedirect.com/...S0960076008000289

Estrogen Estrone aromatase aromatase activity prostate cancer disease men male health

shared by Nathan Goodyear on 21 Aug 13 - No Cached
  • Nathan Goodyear on 21 Aug 13
     
    High Estrone (E1) associated with increased prostate cancer risk.  This occurs through high aromatase activity.
Nathan Goodyear

Role of Polymorphic Human Cytochrome P450 Enzymes in Estrone Oxidation - 0 views

cebp.aacrjournals.org/...551.long

estrogen metabolism estrogen metabolites cytochrome P450 estrogen estrone hormones detoxification metabolites

shared by Nathan Goodyear on 11 Sep 15 - No Cached
  • CYP1A1 and CYP1B1 are not expressed in any significant quantity in the liver. Therefore, they would not be expected to contribute to the overall systemic metabolism of estrone. However, both enzymes have been identified in breast tissue
  • CYP1A1 displayed relatively high activity for all three hydroxylations, suggesting that it may play an important role in extrahepatic tissues where it is expressed
  • CYP1A1 was more active with regard to 2-hydroxylation and 4-hydroxylation, it also displayed one of the greatest 16α-hydroxylating activities of the CYP enzymes tested.
  • ...4 more annotations...
  • CYP1B1 displayed a high affinity for estrone and preferentially catalyzed 4-hydroxylation over 2-hydroxylation
  • CYP1B1 did not seem to contribute to 16α-hydroxylation.
  • CYP1B1 was shown to preferentially catalyze 4-hydroxylation, whereas CYP1A1 was shown to preferentially catalyze 2-hydroxylation
  • Among the CYP enzymes expressed in the liver, CYP1A2 was the most active with regard to 2-hydroxylation
  • Nathan Goodyear on 11 Sep 15
     
    good discussion of estrogen metabolism and the P450 enzymes.
Nathan Goodyear

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

www.ncbi.nlm.nih.gov/...PMC3283536

estrogen metabolism estrogen metabolism breast cancer breast cancer

shared by Nathan Goodyear on 14 Oct 13 - No Cached
  • 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
  • ...6 more annotations...
  • 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
  • Nathan Goodyear on 14 Oct 13
     
    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

Nongenomic actions of estradiol compared with estrone and estriol in pituitary tumor ce... - 0 views

www.ncbi.nlm.nih.gov/...PMC2518256

Estradiol Estrone Estriol Estrogens Estrogen hormone hormones

shared by Nathan Goodyear on 09 Aug 14 - No Cached
  • Nathan Goodyear on 09 Aug 14
     
    good discussion of the nongenomic signaling that occurs from Estradiol, Estrone, and Estriol.
Nathan Goodyear

Estrogen Metabolism and Breast Cancer : Epidemiology - 0 views

journals.lww.com/...lism_and_Breast_Cancer.15.aspx

estrogen metabolism estrogen metabolism estrogen metabolite metabolite metabolites breast cancer 2-OH-estrone 16alpha-OH-estrone 2:16alpha-OHE1

shared by Nathan Goodyear on 21 Aug 14 - No Cached
  • Nathan Goodyear on 21 Aug 14
     
    Maybe the risks of estrogen metabolism is age dependent?  This Long Island Breast Cancer Study Project found that an increased 2:16alphOH-estrone ratio was associated with a reduced premenopausal, invasive breast cancer risk.  This association declined when looked at in postmenopausal women.
Nathan Goodyear

Urinary Hydroxyestrogens and Breast Cancer Risk among Postmenopausal Women: A Prospecti... - 0 views

cebp.aacrjournals.org/...2137.short

estrogen metabolism estrogen metabolism estrone breast cancer risk post-menopause post menopause HRT hormone therapy 2-OH-estrone

shared by Nathan Goodyear on 21 Aug 14 - No Cached
  • Nathan Goodyear on 21 Aug 14
     
    study finds increases risk of breast cancer in postmenopausal women on HRT with increased 2OH-estrone metabolism.  Confusing?
Nathan Goodyear

Postmenopausal breast cancer risk in r... [Cancer Causes Control. 2003] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...14575357

breast cancer cancer estrone estradiol testosterone hormone hormones

shared by Nathan Goodyear on 12 Jun 13 - No Cached
  • Nathan Goodyear on 12 Jun 13
     
    Breast cancer associated with high levels of estrone, estradiol, testosterone, and less with androstenedione and DHEAS.  Those individuals being doped by physicians (a whole lot) are increasing their risk of many health diseases, including breast cancer.
Nathan Goodyear

Evidence for hyperoestrogenaemia as a risk factor for... [Lancet. 1976] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/59076

aromatase aromatase activity testosterone estrogen estradiol estrone MI myocardial infarction low libido gynecomastia low T

shared by Nathan Goodyear on 08 Jun 13 - No Cached
  • Nathan Goodyear on 08 Jun 13
     
    This is just an abstract due to the publication date.  However, this study, though small, found that elevated estradiol and estrone levels preceded myocardial infarctions in small study group (15).  The surprise was that physical symptoms of slow beard growth, loss of libido, and gynecomastia preceded the events.  Also, the testosterone levels were normal.  Got that: elevated estrogen levels with normal testosterone levels result in significant symptoms.
Nathan Goodyear

Sex hormones and cognitive decline ... [Psychoneuroendocrinology. 2009] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...18845400

men estrogen estradiol estrone dementia cognitive decline low T low testosterone hormones hormone

shared by Nathan Goodyear on 30 Apr 13 - No Cached
  • Nathan Goodyear on 30 Apr 13
     
    increased estradiol and estrone levels in men associated with cognitive decline.  This was distinct from age, CVD, and APOE genotype.  This points to a clear association between increased aromatase activity and inflammation that contributes to cognitive decline in men.
Nathan Goodyear

Increased Endogenous Estrogen Synthesis Leads to the Sequential Induction of Prostatic ... - 0 views

www.ncbi.nlm.nih.gov/...PMC2731137

aromatase activity estrogen estradiol estrone testosterone prostate cancer prostatitis inflammation

shared by Nathan Goodyear on 26 Apr 12 - No Cached
  • Nathan Goodyear on 26 Apr 12
     
    study shows that over expression of aromatase activity and resultant increased estradiol/estrone production increases prostatitis and plays a role in prostate cancer.  
Nathan Goodyear

Stimulation of aromatase activity in bre... [Mol Cell Endocrinol. 1994] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...7895904

inflammatory cytokines inflammation TNF-alpha aromatase activity estrone testosterone adipose fat tissue breast men women hormones androstenedione

shared by Nathan Goodyear on 29 Apr 12 - No Cached
  • Nathan Goodyear on 29 Apr 12
     
    inflammatory cytokine, TNF-alpha, increases aromatase activity.  This article discusses the increased production of estrone from androstenedione from aromatase activity in fat tissue in the breast.
Nathan Goodyear

Anterior prostate epithelial AR inactivation modifies estrogen receptor expression and ... - 0 views

ajpendo.physiology.org/...E727.abstract

prostate men male ER-alpha ER-beta estrogen receptors inflammation Testosterone Estradiol Estrone aromatase BPH

shared by Nathan Goodyear on 18 Sep 12 - No Cached
  • Nathan Goodyear on 18 Sep 12
     
    Study shows that decreased androgens up regulates estrogen receptor alpha.  ER alpha promotes growth preferentially over ER beta, and is inflammatory.  Thus in the picture of low T, increased aromatase activity and thus increase Estradiol/Estrone production, we should not be surprised to find increased stimulus for prostate growth.
Nathan Goodyear

Longitudinal and cross-sectional rel... [J Clin Endocrinol Metab. 2014] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...24552220

low T Testosterone elderly men E1 Estrone health male hormone hormones men's health

shared by Nathan Goodyear on 24 Feb 14 - No Cached
  • Nathan Goodyear on 24 Feb 14
     
    This study found that lower TT and E1 associated with more "poor health" as defined by questionnaire.  The conclusion might lead one to think that Estrogen therapy is need in men.  Eightly percent of estrogen production in men occurs from Testosterone.  If Testosterone declines, then estrogen production will likewise decline.  A simple fact that the authors did not comment on.  Also, E1 binds with high affinity to ER alpha, which is pro-inflammatory and pro-proliferative: neither of which is a positive health benefit.   This appears to point more to a broad HPA suppression as an association to the "poor health".
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