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Nathan Goodyear

Exercise-related Changes in Estrogen Metabolism May Lower Breast Cancer Risk - 0 views

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    Aerobic exercise improves estrogen metabolism and may reduce risk of breast cancer.
Nathan Goodyear

Iodine Alters Gene Expression in the MCF7 Breast Cancer Cell Line: Evidence for an Anti... - 0 views

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    Iodine shown to elicit anti-estrogenic effect through altering estrogen metabolization through cyp 1A1instead of the cyp 1B1 pathway.  Important implications in the breast health of women.
Nathan Goodyear

PLOS ONE: Estrogen Signalling and the Metabolic Syndrome: Targeting the Hepatic Estroge... - 0 views

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    Estrogen associated with improved MetS.  This study finds that it is not through the ER alpha receptor.
Nathan Goodyear

Hormonal Modulation in Aging Patients with Erectile Dysfunction and Metabolic Syndrome - 0 views

  • Hypogonadism and MetS are strongly associated [12, 13, 16], having even been demonstrated that with the increasing number of MetS parameters there is a proportional raise in the incidence of hypogonadism
  • increasing number of MetS components is inversely associated with T levels
  • the presence of MetS did not prove to be a significant determinant of hypogonadism, as it did not lead to a decline in T levels, in MetS patients with already established hypogonadism, the increasing number of MetS features was associated with further decline in T
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  • In the setting of MetS, hypertriglyceridemia and increased WC have been reported as the most important determinants of hypogonadism
  • recent literature consistently associates obesity not only with higher risk of hypogonadism [4, 6, 27] but also with lower T levels
  • Visceral adiposity has been particularly related with reduction of T and SHBG levels (independent of other metabolic disorders)
  • WC was one of the MetS parameters with the greatest influence in T levels decrease, presenting itself as a strong risk factor for hypogonadism development
  • MetS-related T decline was not accompanied by an increase in pituitary LH levels, suggesting impairment in gonadotropin secretion
  • The molecules behind this smoothing compensatory effect of GnRH/LH are still unknown, but estrogens and insulin, as well as leptin, TNF-α, and other adipokines, were proposed candidates
  • fat stores undertake an increase aromatization of androgens, therefore raising estrogen levels [9, 15], which in turn decrease LH secretion
  • our data contradicts the concept that estradiol exerts a negative feedback on hypothalamic GnRH secretion
  • taking into account that high estradiol levels have already been described as the only abnormality in a subset of patients with ED, the hypothesis that the later might not only be caused by androgen deficiency is becoming increasingly evident
  • it has been reported that the chronic exposure to phosphodiesterase type 5 inhibitors (PDE5i), widely used for the treatment of ED, may influence serum estradiol levels
  • thyroid disorders (specially hyperthyroidism) have been related to ED and hypogonadism, and so must be considered in a sexual-dysfunction setting
  • It is clear from the current literature that collecting a more thorough hormonal panel might be a wise approach to further uncover hormonal relations
    • Nathan Goodyear
       
      outstanding point.  This hits to the point that Low T is the effect not the cause.
  • We concluded that in ED patients with hypogonadism and MetS, the attenuated response of HPG axis (normal or low LH levels) might not always be due to an underlying adiposity-dependent estrogen-raising effect.
  • our findings indicate that ED, aging, and estradiol might have a stronger connection than what is currently described in the literature.
  • this study underlines the importance of the collection of a full hormonal panel in ED men
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    low T strongly associated with metabolic syndrome in men.
Nathan Goodyear

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

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    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

Does a man's estrogen level impact his risk of prostate cancer? - 0 views

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    How you metabolize your estrogens, increases your risk of prostate cancer
Nathan Goodyear

Testosterone and benign prostatic hyperplasia Jarvis TR, Chughtai B, Kaplan SA, - Asian... - 0 views

  • The prevalence of hypogonadism (often defined as serum testosterone < 300 ng dl−1 ) ranges from 6% [10] to as high as 38%
  • The process of BPH, however, continues as men age and despite the fact their serum testosterone decreases
  • Liu et al. [12] demonstrated that in a group of older males (mean age 59.8 years) that there was not a significant correlation of serum testosterone levels (total, free or bioavailable) with either prostate volume or International Prostate Symptom Score (IPSS)
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  • in eugonadal men, studies have demonstrated that the prostate can increase in volume by approximately 12%
  • There seems to be little doubt that the treatment with testosterone of a young hypogonadal male leads to significant growth of the prostate
  • Behre et al. [22] demonstrated increased prostate volume and prostate-specific antigen (PSA) levels in hypogonadal men
  • Most studies, however, have shown no effect of exogenous androgens on PSA or prostate volume for older hypogonadal males
  • saturation model
  • They argue that the prostate is relatively insensitive to changes in androgen concentration at normal levels or in mild hypogonadism because the AR is saturated by androgens and therefore maximal androgen-AR binding is achieved. Conversely, the prostate is very sensitive to changes in androgen levels when testosterone is low
  • visceral obesity (one of the most significant components of metabolic syndrome) is associated with prostate volume and influences prostate growth during TRT.
  • This hypothesis of inflammation induced LUTS is also argued to be a mechanism for improvement of LUTS with PDE5I
  • The concept, therefore, that treatment with TRT of hypogonadal males with metabolic syndrome might lead to improvement/stabilization of their LUTS, appears to be confirmed in recent work by Francomano et al.
  • There was also an improvement in components of the patient's metabolic syndrome (such as BMI, waist circumference, hemoglobin A1c [HbA1c], insulin sensitivity, and lipid profile) as well as inflammatory markers and C-reactive protein.
  • They concluded that TRT was safe in this group of men, and hypothesize that TRT mitigates the pro-inflammatory factors associated with metabolic syndrome.
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    Authors review the literature behind Testosterone and BPH.  The authors highlight the 4 proposed theories behind BPH: Testosterone, Estrogen, inflammation, and metabolic.   The conclusion is mixed: pointing out that no high level of evidence exists on either side of the debate of Testosterone and BPH.
Nathan Goodyear

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

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

Estrogens and Their Genotoxic Metabolites Are Increased in Obese Prepubertal Girls: The... - 0 views

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    Obesity in young girls increases Estradiol production compared to thin young girls.  Obesity increased  the Estrogen metabolite 16lpha-OH-E1  and this positively correlated with IL-6. 
Nathan Goodyear

Cytochrome P450-mediated metabolism of - PubMed Mobile - 0 views

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    Just the abstract here, but a good review of CYP and estrogen metabolism
Nathan Goodyear

Testosterone and metabolic syndrome Cunningham GR - Asian J Androl - 0 views

  • The relationship of low testosterone to MetS often is considered to be bidirectional; however, the relationships probably are not direct
  • Many of the components of the MetS are recognized risk factors for the development of cardiovascular disease (CVD)
  • Multiple cross-sectional studies have found low TT and low sex hormone binding globulin (SHBG) levels in Caucasian and African-American men with the MetS, irrespective of age
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  • Low TT and SHBG levels also are prevalent in Chinese [7],[8] and Korean [9] men with the MetS
  • Normally 40%-50% of TT is bound to SHBG, so reducing SHBG levels will decrease TT.
  • Hyperinsulinism suppresses SHBG synthesis and secretion by the liver
  • significant increase in SHBG levels occurred after acutely lowering insulin levels in obese men
  • Estradiol levels are increased in men with the MetS, and they are positively correlated with the number of abnormal components of the MetS.
  • Although it is known that estrogen will increase SHBG levels, apparently the hyperinsulinism associated with obesity has a greater effect on SHBG levels
  • Estradiol also can inhibit luteinizing hormone (LH) secretion
  • Inflammatory cytokines are thought to have a direct effect on the pituitary to reduce LH secretion [15] and also a direct effect on Leydig cell secretion of testosterone
  • Low TT Levels have been shown to predict development of the MetS in men with normal BMI
  • Men in the lowest quartiles of serum TT, calculated free testosterone (cFT) and SHBG at baseline had the highest odds ratios for developing the MetS or DM during the 11 years follow-up
  • More recently, investigators conducting population-based studies have reported that only SHBG is associated with future development of the MetS
  • Additional evidence that low TT increases the risk of MetS comes from androgen deprivation treatment of prostate cancer
  • Low TT and low bioavailable testosterone (bT) were each significantly associated with elevated 20 years risk of CVD mortality in an older population in which cause-specific mortality was age, adiposity, and lifestyle-adjusted.
  • combination of low bT and ATP III-defined MetS is associated with increased cardiovascular mortality in men aged 40 years and above
  • in elderly men, testosterone may weakly protect against CVD. Alternatively, low TT may indicate poor general health
  • Muraleedharan and Jones [27] concluded that there is convincing evidence that low T is a biomarker for disease severity and mortality.
  • The evidence that TRT improves insulin sensitivity and glucose control is conflicted
  • It is widely recognized that testosterone treatment can reduce fat mass and increase lean body mass; however, until recently most reports have not been associated with much weight loss
  • Changes in body composition and weight loss are considered potential mechanisms by which testosterone treatment improves insulin sensitivity and glucose control in patients with diabetes. Effects on inflammatory cytokines [38] and changes in oxidative metabolism [39] also have been reported to improve glucose metabolism.
  • Testosterone replacement therapy has been reported to improve some or all of the components of the MetS.
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    To be read article on Testosterone and Metabolic Syndrome.
Nathan Goodyear

Estradiol and Metabolic Syndrome in Older Italian Men: the InCHIANTI Study - 0 views

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    Men with metabolic syndrome found to be associated with higher Estradiol levels.  Thus, Estradiol in "older men", >65 in this study, is associated with metabolic syndrome.
Nathan Goodyear

On Estrogen, Cholesterol Metabolism, and Breast Cancer - NEJM - 1 views

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    Cholesterol metabolite linked to increased breast cancer risk through estrogen receptor signaling.  The metabolite is 27-hydorxycholesterol.
Nathan Goodyear

Relationship of serum estrogens and estrogen metabolites to postmenopausal breast cance... - 0 views

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    Increased metabolism down the 2 hydroxylation pathway appears to reduce postmenopausal breast cancer risk.
Nathan Goodyear

A Radioimmunoassay for 3,3',5'-L-Triiodothyronine (Reverse T3): Assessment of Thyroid G... - 0 views

  • Both pregnancy and estrogen administration were associated with increases in serum reverse T3 concentrations presumably because of their ability to augment thyroxine binding globulin synthesis.
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    oral estrogen supplementation increase reverse T3 and lowers metabolism and leads to weight gain
Nathan Goodyear

ScienceDirect.com - Cell Metabolism - Estrogen Receptors and the Metabolic Network - 0 views

  • The pro-opiomelanocortin (POMC) neurons have an anorexigenic action and, when activated, reduce food intake through the release of two peptides, α-melanocyte-stimulating hormone (α-MSH) and cocaine-and-amphetamine-regulated transcripts (CART). The neuropeptide Y (NPY) neurons, on the other hand, release NPY hormone and agouti gene-related protein (AgRP), which prevent the binding of α-MSH to MC3R and MC4R, increasing food intake
  • This suggests that the central anorexic effects of E2 may occur via ERβ
  • The main hypothalamic areas involved in food intake and satiety are the arcuate nucleus (ARC), the lateral hypothalamus (LH), the paraventricular nucleus (PVN), the ventromedial hypothalamus (VMH), and the dorsomedial hypothalamus (DMH)
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  • Leptin is a potent anorexigenic and catabolic hormone secreted by adipose cells that reduces food intake and increases energy expenditure
  • E2 not only modulates leptin receptor mRNA in the ARC and VMH, but also increases hypothalamic sensitivity to leptin, altering peripheral fat distribution
  • ghrelin. It acts on growth hormone secretagogue receptors (GHSR1a) located in the ARC and is a potent stimulator of food intake
  • It thus appears that of the two ERs, ERα plays a predominant role in the CNS regulation of lipid and carbohydrate homeostasis.
  • Both ERs have been identified in the ARC
  • Stimulation of MCH neurons increases food intake and fat accumulation while its inhibition leads to decreased food intake and reduced fat accumulation.
  • Both ERs have been identified in the LH
  • both ERs have been identified in this nucleus
  • The PVN is the region of the hypothalamus with the highest expression of ERβ and is reported to be weakly ERα positive
  • The VMH is ERα regulated
  • Skeletal muscle is responsible for 75% of the insulin-induced glucose uptake in the body
  • GLUT4 is highly expressed in muscle and represents a rate-limiting step in the insulin-induced glucose uptake
  • data suggest that in the physiological range, E2 is beneficial for insulin sensitivity, whereas hypo- or hyperestrogenism is related to insulin resistance
  • In aging female rats, E2 treatment improves glucose homeostasis mainly through its ability to increase muscle GLUT4 content on the cell membrane
  • It is evident that ERα and ERβ have distinct actions and that much more research is needed to clearly identify the function of each receptor in muscle.
  • E2 prevents accumulation of visceral fat, increases central sensitivity to leptin, increases the expression of insulin receptors in adipocytes, and decreases the lipogenic activity of lipoprotein lipase in adipose tissue
  • In rats, ovariectomy increases body weight, intra-abdominal fat, fasting glucose and insulin levels, and insulin resistance followed by decreased phosphorylation of AMPK and its substrate acetyl-CoA carboxylase in adipose tissue
  • decreased adiponectin, PPARγ coactivator-1α (PGC-1α), and uncoupling protein 2 (UCP2) and increased resistin
  • Men with aromatase deficiency have truncal obesity, elevated blood lipids, and severe insulin resistance
  • Although not all studies are in agreement, polymorphisms of ERα in humans have been associated with risk factors for CVDs
  • Human subcutaneous and visceral adipose tissues express both ERα and ERβ, whereas only ERα mRNA has been identified in brown adipose tissue
  • suggesting that ERα is the main regulator of GLUT4 expression in adipose tissue
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    very nice article that looks at the balance of ER-alpha/ER-beta and their role in metabolic syndrome.  This article discusses the balance of  these receptors are tissue dependent in their effect.  I like their conclusion: "...but these mechanisms will never be completely understood if they are not considered in the context of a whole system.
Nathan Goodyear

Impact of Metabolic Syndrome on Benign Prostatic Hy... [Urol Int. 2014] - PubMed - NCBI - 0 views

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    Metabolic syndrome associated with increased risk of prostate enlargement in elderly Chinese men.  The study highlighted insulin resistance as a key risk.  Insulin resistance is known to increase aromatase activity and thus estrogen production which will increase prostate growth.
Nathan Goodyear

Chemistry and Structural Biology of Androgen Receptor - 0 views

  • 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
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  • 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
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    good review of androgens and AR.
Nathan Goodyear

Urine Biomarkers of Risk in the Molecular Etiology of Breast Cancer - 0 views

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    Estrogen metabolism, markers, and urine.
Nathan Goodyear

KoreaMed Synapse - 0 views

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    Metabolic syndrome incidence increases with menopause and low estrogen in women.
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