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    Role of Estradiol in Men and Its Management

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    Check your estradiol (sensitive) blood levels cheaply: DiscountedLabs.com






    By Nelson Vergel, BsChE, MBA

    Testosterone is the precursor hormone for estradiol. Estradiol is a hormone more abundant in women than men that is produced by the aromatization of testosterone in liver, fat and other cells. Nature created it for a reason. It has been shown to be responsible for healthy bone density but its role in men's sex drive, body composition and other variables is source of great debate. One thing is certain: High estradiol blood levels can cause growth of breast tissue in men :http://www.excelmale.com/threads/442...ight=man+boobs

    When the HPT hormonal axis senses that testosterone or estradiol are high, it automatically decreases or shuts down testosterone production.

    Many anti-aging or men's health clinics prescribe anastrozole, a blocker of estradiol production, to men who start testosterone replacement (TRT). Higher estradiol blood levels not only can cause breast tissue growth (gynecomastia) but also water retention (edema). Some people speculate that high estradiol can also lead to erectile dysfunction but no scientific papers have been published on this subject. Since higher testosterone blood levels can originate higher estradiol levels, the belief is that using anastrozole will prevent breast tissue growth and erectile dysfunction by lowering any potential increase in estradiol. However, we have no data on how high is too high when it comes to this hormone in men. Some even speculate that low testosterone-to-estradiol ratios may be more closely correlated to gynecomastia and erectile problems than estradiol alone.

    The truth about these speculations is starting to emerge but we still do not have enough data to say what the upper value of the optimal range of estradiol really is. We have a lot of evidence about the lower side of the optimal range since it has been found that estradiol blood levels below 10-20 pg/ml can increase bone loss in men. A recently published study also nicely demonstrated that low estradiol can be associated with higher fat mass and lower sexual function in men. So, be very careful when a clinic wants to put you on this drug without first justifying its use.

    Another concerning fact is that many clinics may be using the wrong estradiol test that may be over-estimating the levels of this hormone in men. An ultrasensitive estradiol test more accurately measures estradiol in men instead of the regular test that costs less.

    Fortunately, most men on TRT do not develop gynecomastia even without using anastrozole (gynecomastia is common in bodybuilders who may use high doses of testosterone, however). Those that have gynecomastia at TRT doses (100-200 mg of injectable testosterone or 5-10 grams of testosterone gel per day) may be genetically predisposed to having more aromatase activity or have liver dysfunction. Treating all men who start TRT with anastrozole from the start may be counterproductive since this may lower estradiol to very low levels. Some physicians monitor estradiol blood levels after 6-8 weeks of having a man start TRT alone using the ultrasensitive estradiol test to determine if anastrozole use is warranted. Doses range from 0.25 mg per week to some clinics using excessive doses of 1 mg three times per week. After 4-6 weeks on anastrozole its dose can be adjusted to ensure than estradiol is not under 20 pg/ml. Fortunately, many men on TRT do not need anastrozole at all.

    So we await for more studies that will clarify the role and optimal ranges of estradiol. Here are a few studies that we already have available based on the role investigated.

    THE ROLE ON ESTROGEN IN MEN:

    From:The Decline of Androgen Levels in Elderly Men and Its Clinical and Therapeutic Implications


    There is a rapidly growing body of evidence that a number of physiological actions of testosterone in men are mediated by the ERs (estrogen receptors) after its biotransformation by the aromatase cytochrome P450 enzyme in the tissues (59). Documented estrogen-mediated actions of testosterone in men include a role in the feedback regulation of LH (60, 61), a role in the regulation of skeletal homeostasis (62, 63), as well as a role in lipid metabolism and cardiovascular physiology (64, 65); among other possible estrogen actions in men, there are indications for a role in the brain (66) and in spermatogenesis (67). These estrogenic actions in men can be exerted by blood-borne estrogens as well as through local aromatization of testosterone in, or in close vicinity of, the target cell. The expression of the CYP19 gene encoding the aromatase enzyme can be differentially regulated according to the tissue (68, 69).

    The conversion rate of testosterone to estradiol is around 0.2%. Up to 80% of plasma estradiol originates from aromatization of testosterone and androstenedione, mainly in (sc) fat and striated muscle, although aromatase activity is present in many other tissues, including bone and the brain; no more than 20% of estradiol in the circulation is secreted by the testes. Estradiol serum concentration in the adult male is around 20 to 30 pg/ml (70 to 110 pmol/liter), with a production rate of around 45 μg/d. Plasma estradiol is also bound to SHBG but with only half the affinity of testosterone. Total plasma estradiol levels in adult men do not vary significantly with age; indeed the decrease in precursor levels (i.e., testosterone and androstenedione) is compensated by an increase of fat mass and tissue aromatase activity with age (36, 70, 71). As a consequence of the age-associated increase in SHBG binding capacity, the serum concentrations of free estradiol and non-SHBG-bound or “bioavailable” estradiol do show a moderate age-associated decrease (36, 71, 72) (Fig. 3). It can be pointed out that estrogen serum levels in elderly males are higher than those in postmenopausal women (63).


    STUDY LOOKING AT THE EFFECT OF ESTRADIOL ON FAT MASS, SEX DRIVE AND ERECTILE FUNCTION


    There was a recently published groundbreaking study about the role of estradiol in men. No optimal ranges of estradiol were noted but low levels were associated with increase fat and decrease in sexual desire and erectile function compared to higher levels (the highest average estradiol was 35 pg/ml unfortunately, so no conclusions can be made for levels above this).

    Men had their hormones blocked by a gonadotropin releasing hormone antagonist. All of them then received testosterone supplementation with Androgel. Half were also treated with anastrozole to block estradiol conversion from the testosterone. Please refer to attached graphs.

    All participants (Cohorts 1 and 2) received goserelin acetate (Zoladex, AstraZeneca), at a dose of 3.6 mg subcutaneously at weeks 0, 4, 8, and 12, to suppress endogenous gonadal steroids (testosterone and estradiol). All participants (Cohort 1 and 2) were then randomly assigned to receive 0 g (placebo), 1.25 g, 2.5 g, 5 g, or 10 g of a topical 1% testosterone gel (AndroGel, Abbott Laboratories) daily for 16 weeks. Participants in cohort 2 also received anastrozole (Arimidex, AstraZeneca) at a dose of 1 mg daily to block the aromatization of testosterone to estrogen. Participants were unaware of the study group assignments.

    Findings:

    Higher blood levels of testosterone decreased the percentage of body fat (P = 0.001), intra abdominal fat area (P = 0.021), and subcutaneous fat area (P = 0.029), and increased sexual desire (P = 0.045) and erectile function (P = 0.032).

    Low blood level of estradiol was associated with significant increases in the percentage of body fat (P<0.001), subcutaneous fat area (P<0.001), and intra abdominal fat area (P = 0.002), and relative less improvement in sexual desire (P<0.001) and erectile function (P = 0.022). These findings provide additional evidence of an independent effect of estradiol on these variables.

    "Our finding that estrogens have a fundamental role in the regulation of body fat and sexual function, coupled with evidence from prior studies of the crucial role of estrogen in bone metabolism, indicates that estrogen deficiency is largely responsible for some of the key consequences of male hypogonadism and suggests that measuring estradiol might be helpful in assessing the risk of sexual dysfunction, bone loss, or fat accumulation in men with hypogonadism. For example, in men with serum testosterone levels of 200 to 400 ng per deciliter, sexual desire scores decreased by 13% if estradiol levels were 10 pg per milliliter or more and by 31% if estradiol levels were below 10 pg per milliliter. "

    Reference:

    Gonadal Steroids and Body Composition, Strength, and Sexual Function in Men
    N Engl J Med 2013;369:1011-22.


    STUDY LOOKING AT EFFECT OF ESTRADIOL ON MORTALITY IN MEN:

    This study found that estradiol levels of < 21.80 pg/ml and > 30.11 pg/ml resulted in greater mortality in men.


    Abstract

    CONTEXT:

    Androgen deficiency is common in men with chronic heart failure (HF) and is associated with increased morbidity and mortality. Estrogens are formed by the aromatization of androgens; therefore, abnormal estrogen metabolism would be anticipated in HF.


    OBJECTIVE:

    To examine the relationship between serum concentration of estradiol and mortality in men with chronic HF and reduced left ventricular ejection fraction (LVEF).


    DESIGN, SETTING, AND PARTICIPANTS:

    A prospective observational study at 2 tertiary cardiology centers (Wroclaw and Zabrze, Poland) of 501 men (mean [SD] age, 58 [12] years) with chronic HF, LVEF of 28% (SD, 8%), and New York Heart Association [NYHA] classes 1, 2, 3, and 4 of 52, 231, 181, and 37, respectively, who were recruited between January 1, 2002, and May 31, 2006. Cohort was divided into quintiles of serum estradiol

    quintile 1, < 12.90 pg/mL;
    quintile 2, 12.90-21.79 pg/mL;
    quintile 3, 21.80-30.11 pg/mL;
    quintile 4, 30.12-37.39 pg/mL;
    and quintile 5, > or = 37.40 pg/mL.

    Quintile 3 was considered prospectively as the reference group.


    MAIN OUTCOME MEASURES:

    Serum concentrations of estradiol and androgens (total testosterone and dehydroepiandrosterone sulfate [DHEA-S]) were measured using immunoassays.


    RESULTS:

    Among 501 men with chronic HF, 171 deaths (34%) occurred during the 3-year follow-up. Compared with quintile 3, men in the lowest and highest estradiol quintiles had increased mortality (adjusted hazard ratio [HR], 4.17; 95% confidence interval [CI], 2.33-7.45 and HR, 2.33; 95% CI, 1.30-4.18; respectively; P < .001). These 2 quintiles had different clinical characteristics (quintile 1: increased serum total testosterone, decreased serum DHEA-S, advanced NYHA class, impaired renal function, and decreased total fat tissue mass; and quintile 5: increased serum bilirubin and liver enzymes, and decreased serum sodium; all P < .05 vs quintile 3). For increasing estradiol quintiles, 3-year survival rates adjusted for clinical variables and androgens were 44.6% (95% CI, 24.4%-63.0%), 65.8% (95% CI, 47.3%-79.2%), 82.4% (95% CI, 69.4%-90.2%), 79.0% (95% CI, 65.5%-87.6%), and 63.6% (95% CI, 46.6%-76.5%); respectively (P < .001).

    Reference:

    Circulating estradiol and mortality in men with systolic chronic heart failure.
    JAMA 2009 May 13;301(18):1892-901.


    STUDY LOOKING AT THE EFFECT OF ESTRADIOL ON BONE DENSITY IN MEN:

    This study followed young and older men's testosterone and estradiol to see their impact on bone density. Estradiol below 11 pg/ml was associated with increased bone loss.

    Abstract

    Estrogen appears to play an important role in determining bone mineral density in men, but it remains unclear whether estrogen primarily determines peak bone mass or also affects bone loss in elderly men. Thus, we assessed longitudinal rates of change in bone mineral density in young (22–39 yr; n = 88) vs. elderly (60–90 yr; n = 130) men and related these to circulating total and bioavailable estrogen and testosterone levels. In young men bone mineral density increased significantly over 4 yr at the mid-radius and ulna and at the total hip (by 0.32–0.43%/yr), whereas it decreased in the elderly men at the forearm sites (by 0.49–0.66%/yr), but did not change at the total hip. The rate of increase in bone mineral density at the forearm sites in the young men was significantly correlated to serum total and bioavailable estradiol and estrone levels (r = 0.22–0.35), but not with total or bioavailable testosterone levels. In the elderly men the rates of bone loss at the forearm sites were most closely associated with serum bioavailable estradiol levels (r = 0.29–0.33) rather than bioavailable testosterone levels. Moreover, elderly men with bioavailable estradiol levels below the median [40 pmol/liter (11 pg/ml)] had significantly higher rates of bone loss and levels of bone resorption markers than men with bioavailable estradiol levels above 40 pmol/liter. These data thus indicate that estrogen plays a key role both in the acquisition of peak bone mass in young men and in bone loss in elderly men. Moreover, our findings suggest that age-related decreases in bioavailable estradiol levels to below 40 pmol/liter may well be the major cause of bone loss in elderly men. This subset of men is perhaps most likely to benefit from preventive therapy.

    Reference:

    Relationship of Serum Sex Steroid Levels to Longitudinal Changes in Bone Density in Young Versus Elderly Men.
    The Journal of Clinical Endocrinology & Metabolism August 1, 2001 vol. 86 no. 83555-3561


    TWO STUDIES LOOKING INTO THE EFFECT OF HIGH ESTRADIOL ON LIBIDO IN MEN ON TESTOSTERONE THERAPY

    I have been warning men and clinics not to be so aggressive treating estradiol in men with the overuse of anastrozole. Here is a recent study done in Houston.

    Attachment 633

    Elevated serum estradiol is associated with increased libido in men receiving testosterone replacement therapy (TRT), according to researchers.

    In a study of 423 men on TRT, Ranjith Ramasamy, MD, working with Larry Lipshultz, MD, at the Baylor College of Medicine in Houston, measured subjects' testosterone and estradiol levels and asked the men to rate the quality of their libido using a five-point Likert scale (1= terrible, 5 = excellent). The researchers categorized the men as having low or high testosterone (below or above 300 ng/dL, respectively) and low or high estradiol (below 5 and above 5 ng/dL (50 pg/mL), respectively).

    Men with high serum testosterone levels reported significantly greater libido than men with low level and those with high serum estradiol levels had significantly greater libido than subjects with low levels. In all, 60.4% of men with both high testosterone and estradiol levels reported very good or excellent libido (score as 4 or 5) compared with 31.3% of participants with both low testosterone and estradiol levels, the researchers reported in European Urology (published online ahead of print). These results are expected to be presented at the American Urological Association annual meeting in Orlando this May.

    http://www.renalandurologynews.com/h...rticle/335894/

    High Estrogen in Men After Injectable Testosterone Therapy

    The Low T Experience

    Robert S. Tan,
    Low T Institute, Southlake, TX, USA
    Robert S. Tan, 3311 Richmond #205, Houston, TX 77098, USA.

    Abstract

    Testosterone replacement improves quality of life and is aromatized in men in adipose tissues to estrogen. Hyperestrogenism is believed to be harmful to male sexuality. This is a description of our experience of screening 34,016 men in the Low T Centers, of which approximately 50% were converted to treatment. Men were treated with injectable testosterone, and we have available data from 2009 to 2014. The data were extracted from our electronic health record (AdvancedMD) of 35 Low T Centers across the United States. In all, 7,215 (20.2%) out of the 34,016 patients had high estradiol levels defined as ≥42.6 pg/ml. Estradiol was measured using electro-chemiluminescence immunoassay. Of the patients who had high estradiol levels, the age distribution was as follows: 132/989 (13.3%) were older than 65 years, 3,753/16,955 (22.1%) were between 45 and 65 years; 2,968/15,857 (18.7%) were between 25 and 44 years, 7/215 (3.3%) were younger than 25 years. The difference between extreme age groups (<25 and ≥65) was statistically significant using a chi-square test (p = .013). The correlation coefficient of serum estradiol to age was .53,SD = 8.21. It was observed that practitioners used aromatase inhibitor and selective estrogen receptor modulator to treat symptoms of hyperestrogenism, irrespective of blood estradiol levels. Gynecomastia was rarely documented as a reason for the prescription. Our finding was that high estradiol levels were not associated with higher rates of low libido but established higher rates of documented low libido with those with normal or lower estradiol levels. The difference was statistically significant (p < .05).


    STUDY LOOKING INTO THE EFFECT OF ESTRADIOL ON BONE DENSITY IN MEN:

    Low blood levels of estradiol is associated with brittle bones in old men: New study.

    Serum Estradiol Levels are Inversely Associated with Cortical Porosity in Older Men.


    J Clin Endocrinol Metab. 2014 Apr 2:jc20141319. [Epub ahead of print]


    Abstract

    Context: The key role of serum estradiol (E2) for bone health in men is well established. The effect of serum sex steroids on bone microstructure, measured by high-resolution peripheral quantitative computed tomography (HRpQCT), remains unknown in elderly men. Objective: To examine the associations between serum sex steroids and bone microstructural parameters in older men. Methods: Trabecular and cortical bone microstructure at the tibia was measured by HRpQCT in 440 men (mean 80 years of age) participating in the population-based MrOS Sweden cohort. Serum levels of E2 and testosterone (T) were analyzed with mass spectrometry and free E2 and free T levels were calculated using law-of-mass-action equations. Results: Age-adjusted models demonstrated that E2 and free E2 but not T or free T associated significantly inversely with cortical porosity. The associations between E2 and free E2 and cortical porosity remained significant after further adjustment for height, weight, physical activity, calcium intake and smoking. Models including both serum E2 and T demonstrated that E2 (standardized beta= -0.12, P<0.05) but not T associated independently with cortical porosity. A similar independent association was found for free E2 (standardized beta= -0.12, P<0.05) but not free T. Free E2 associated significantly with trabecular bone volume fraction in age-adjusted models but this association did not remain significant after further adjustment. Conclusions: Serum E2 levels associated inversely with cortical porosity in 80-year-old men. We propose that low serum E2 may reduce cortical bone strength, at least partly by increasing cortical porosity, and, thereby, increase fracture risk in older men.


    STUDY LOOKING INTO THE EFFECT OF ESTRADIOL ON HEMOGLOBIN IN MEN:

    Serum estradiol associates with blood hemoglobin in elderly men; The MrOS Sweden Study. The Journal of Clinical Endocrinology & Metabolism.http://press.endocrine.org/doi/abs/10.1210/jc.2013-4111


    Context: Blood hemoglobin (Hb) declines with age in healthy elderly men, in whom decreasing testosterone has been regarded as part of normal ageing. However, the association between Hb and serum estradiol is incompletely known.


    Objective: To determine whether estradiol is associated with anemia/Hb and established determinants of Hb in elderly men without prostate cancer.


    Design, Setting and Participants: The MrOS (Osteoporotic Fractures in Men) is a population-based study (n=918, median age 75.3 years, range 70–81 years).


    Main Outcome Measures: We evaluated total estradiol in relation to Hb and adjusted for potential confounders (i.e. age, body mass index (BMI), erythropoietin (EPO), total testosterone, cystatin C, iron- and B-vitamin status).


    Results: Estradiol correlated negatively with age (r=-0.14, p<0.001). Hb correlated (age adjusted) positively with estradiol (r=0.21, p<0.001) and testosterone (r=0.10, p<0.01). Independent predictors for Hb in multivariate analyses were estradiol, EPO, BMI, transferrin saturation, cystatin C and free T4 but not testosterone.


    After exclusion of subjects with Hb <130g/L and/or testosterone <8 nmol/L (n=99), the correlation between Hb and testosterone was no longer significant, whereas the associations between Hb and estradiol remained. After adjusting for age, BMI and EPO, men with lower estradiol levels were more likely to have Hb in the lowest quartile of values [OR per SD decrease in estradiol = 1.61 (95% CI 1.34–1.93)]. Anemic subjects (Hb <130 g/L) had lower mean estradiol than non-anemic (67.4 vs 79.4 pmol/L, p<0.001).


    Conclusions: Estradiol correlated, positively and independently, with Hb. Decreased estradiol might partly explain the age-related Hb decline observed in healthy elderly men.



    RECOMMENDED ULTRASENSITIVE ESTRADIOL BLOOD TESTS FOR MEN:


    Comparisons of Immunoassay and Mass Spectrometry Measurements of Serum Estradiol Levels and Their Influence on Clinical Association Studies in Men



    "In conclusion, our findings suggest interference in the standard immunoassay-based E2 analyses, possibly by CRP or a CRP-associated factor. Although this interference does not seem to affect association studies between immunoassay E2 levels and skeletal parameters, we propose a reevaluation of previous association studies between immunoassay-based E2 levels and inflammation-related outcomes. In addition, MS-based assays are to be preferred for the quantification of E2 levels in men."


    Scientific paper comparing the regular estradiol test to the sensitive estradiol in men and postmenopausal women.http://ajcp.ascpjournals.org/content/129/4/530.full.pdf


    This is the most precise estradiol test for me provided by Labcorp:

    Estradiol, LCMS (Endocrine Sciences)


    Test Number: 500108 CPT Code: 82670
    Specimen: Serum (preferred) or plasma, frozen
    Volume: 3 mL
    Minimum Volume: 1.5 mL (Note: This volume does not allow for repeat testing.)
    Container: Gel-barrier tube, lavender-top (EDTA) tube, or green-top (heparin) tube
    Collection: Serum/plasma must be separated from cells within 45 minutes of venipuncture. Send serum/plasma in a plastic transport tube. To avoid delays in turnaround time when requesting multiple tests on frozen samples, please submit separate frozen specimens for each test requested.
    Storage Instructions: Freeze. Stable at room temperature or refrigerated for two days. Stable for two years frozen.
    Methodology: Liquid chromatography/tandem mass spectrometry (LC/MS-MS)


    This is the test performed by Quest Diagnostics:

    Estradiol, Ultrasensitive, LC/MS/MS

    Test Code
    30289

    CPT Code(s)
    82670

    Preferred Specimen(s)
    0.5 mL serum collected in a red-top tube (no gel)

    Minimum Volume
    0.2 mL

    Collection Instructions
    Specify age and sex on test request form. Plasma, fluid and serum collected in SST's are not acceptable specimen types.Ship frozen. Do not thaw.

    Transport Temperature
    Frozen

    Specimen Stability
    Room temperature: 48 hours
    Refrigerated: 7 days
    Frozen: 2 years

    Methodology
    Liquid Chromatography Tandem Mass Spectrometry (LC/MS/MS)


    ********************
    This is an estradiol distribution table/graph in women and men with certain hormone disorders (immunoassay test)

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    Source: http://www.ncbi.nlm.nih.gov/pubmed/1201738
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    Last edited by Nelson Vergel; 10-09-2016 at 10:55 PM.

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    This study shows what happens to sexual function and body composition at different blood levels of testosterone and/or estradiol.


    Gonadal Steroids and Body Composition, Strength, and Sexual Function in Men

    N Engl J Med. Sep 12, 2013; 369(11): 1011–1022.

    All participants received goserelin acetate (Zoladex, AstraZeneca), at a dose of 3.6 mg subcutaneously at weeks 0, 4, 8, and 12, to suppress endogenous gonadal steroids. Participants were then randomly assigned to receive 0 g (placebo), 1.25 g, 2.5 g, 5 g, or 10 g of a topical 1% testosterone gel (AndroGel, Abbott Laboratories) daily for 16 weeks. Participants in cohort 2 also received anastrozole (Arimidex, AstraZeneca) at a dose of 1 mg daily to block the aromatization of testosterone to estrogen. Participants were unaware of the study-group assignments.
    Participants were seen every 4 weeks. At each visit, fasting blood samples were obtained to measure gonadal steroid levels, and questionnaires were administered to assess physical function, health status, vitality, and sexual function. At baseline and week 16, body fat and lean mass were assessed by means of dual-energy x-ray absorptiometry (DXA); subcutaneous- and intraabdominal-fat areas and thigh-muscle area were measured by means of computed tomography (CT); and lower-extremity strength was determined by means of a leg press. Data on bone homeostasis (bone-turnover markers and bone mineral density), risk factors for cardiovascular disease (blood pressure, lipids, and insulin sensitivity), and levels of leptin and prostate-specific antigen were also collected but are not included in the present report.

    "...we found that lean mass, muscle size, and strength are regulated by androgens (testosterone); fat accumulation is primarily a consequence of estrogen deficiency (low estradiol); and sexual function is regulated by both androgens and estrogens. Delineation of the degrees of hypogonadism at which undesirable consequences develop and of the relative roles of androgens (testosterone) and estrogens in each outcome should facilitate the development of more rational approaches to the diagnosis and treatment of hypogonadism in men."

    Attachment 958

    Attachment 959

    Attachment 959

    Source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4142768/
    Attached Images Attached Images    
    Last edited by Nelson Vergel; 08-27-2014 at 05:52 PM.

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    More estradiol related posts on ExcelMale.com:
    http://www.excelmale.com/tags.php?tag=estradiol

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    The study posted in the second post above showed that low estradiol may be linked to higher fat in men. Here is a study done in female rats that is pretty much concluding the same thing.

    Estradiol May Prevent Fat Accumulation



    At least in female rodents...


    "administration of supplemental doses of estradiol appeared to prevent fat accumulation and overcome leptin resistance in ovarian-intact and ovariectomized female high-fat-diet mice, thy wrote online in the journal Endocrinology.
    But response to estradiol treatment in the high-fat-diet animals depended on endogenous estrogenic status, they cautioned.
    "When estradiol (E2) was cyclically administered to ovarian-intact HFD-fed mice for 12 weeks, the animals gained significantly less weight than ovarian-intact vehicle controls (P<0.01)," the researchers wrote. "This difference was mainly due to reduced caloric intake and not to an increase in energy expenditure or locomotor activity."


    http://www.medpagetoday.com/Endocrin...rinology/47530

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    Finally, a good article on estradiol and aromatase inhibitors!!

    "Truthfully, it is impossible to state whether anyone has been harmed by using aromatase inhibitors for performance- or physique-enhancement; it simply is not tracked. These two drugs are oral (a similar drug, Aromasin®, is injected); they generally do not cause physically perceived, short-term symptoms; and they are rarely used long-term. These factors instill a false sense of security in users.

    Yet, there are problems that may arise as a result of aromatase inhibition, particularly aggressive aromatase inhibition that suppresses estrogen concentrations to very low values. Estrogen (primarily estradiol, but let's stay with the generic term estrogen for simplicity's sake) is not a metabolic waste product in men, a primordial remnant of no greater perceived value than the appendix. It is a functioning hormone that is anabolic in some tissues (e.g., bone, fat, breast); a stimulatory hormone (i.e., enhances production of certain circulating proteins in the liver); a metabolic modifier (affects endocrine hormones as well as carrier protein concentrations, such as binding globulins for vitamin D and sex hormones); a neurosteroid affecting neurotransmitter action, behavior, and emotions; an endocrine regulator; and has other functions.

    It is irrational to think that there would not be hazards when concentrations are artificially suppressed well below the lowest extreme of the physiologic range, just as occurs when estrogen is elevated past the upper limit of normal. What, then, are some of the possible consequences to creating an estrogen deficiency in adult males?"
    http://musculardevelopment.com/artic...l#.VFERIvTF_Cr

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    Last edited by Nelson Vergel; 05-24-2017 at 05:28 AM.

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    High estradiol (not testosterone) was detected in men with prostate cancer when compared to healthy men.

    Serum Testosterone, 17β-Estradiol and PSA Levels in Subjects with Prostate Disorders.


    Usoro et al


    Indian J Clin Biochem. 2015 Jan;30(1):59-65. doi: 10.1007/s12291-013-0411-3. Epub 2014 Jan 29.


    Abstract

    Prostate carcinoma is the most frequently diagnosed malignancy and the second leading cause of death as a result of cancer in men in the US and other parts of the world. There are conflicting reports on the serum levels of testosterone and 17β-estradiol (E2) in benign prostatic hyperplasia (BPH) and prostate cancer. This study was designed to evaluate the serum concentrations of these hormones in patients with these disorders. Serum levels of prostate specific antigen (PSA), total testosterone and estradiol were determined in 228 subjects comprising of 116 subjects with BPH, 62 subjects with prostate cancer (CaP) and 50 age-matched apparently healthy controls, using ELISA methods. PSA levels were significantly elevated (p < 0.05) in BPH subjects than controls, while there was no significant difference (p > 0.05) in testosterone and estradiol levels of these subjects. PSA and estradiol levels were significantly higher (p < 0.05) in CaP subjects than in controls, while there was no observed significant difference (p > 0.05) in testosterone levels. CaP subjects had significantly raised PSA, testosterone, and estradiol levels than BPH subjects. The mean molar ratio of testosterone: E2 was lowest among CaP patients (134:1) and highest among controls (166:1). Significant positive correlation between PSA and 17β-estradiol was observed in prostate disorders (BPH and CaP patients: r = 0.347; p = 0.000). Significant negative correlations between testosterone and PSA were also observed among BPH patients (r = -0.221, p = 0.049) and control subjects (r = -0.490, p = 0.000). No significant correlation existed between testosterone and PSA in CaP patients (r = 0.051, p = 0.693). Correlations between age and estradiol in both BPH and CaP were not significant (p > 0.05). This study has shown that, there was a significant increase in serum estradiol in CaP subjects, while the testosterone levels in both BPH and CaP subjects were not different from those of controls.

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    The Anxiolytic and Antidepressant-like Effects of Testosterone and Estrogen in Gonadectomized Male Rat

    http://dx.doi.org/10.1016/j.biopsych.2014.12.024

    Abstract

    Background

    While the influence of testosterone levels on vulnerability to affective disorders is not straightforward, research suggests this hormone may confer some degree of resiliency in men. We recently demonstrated a role for the dentate gyrus in mediating testosterone’s protective effects on depressive-like behavior in gonadectomized male rats. Here, testosterone may exert its effects through androgen receptor-mediated mechanisms or via local aromatization to estradiol.

    Methods

    Gonadectomized male rats were implanted with a placebo, testosterone, or estradiol pellet, and subsequent protective anxiolytic- and antidepressant-like effects of testosterone and its aromatized metabolite, estradiol, were then investigated in the open field and sucrose preference tests, respectively. Moreover, their influence on gene expression in the hippocampus was analyzed by genome-wide complementary DNA microarray analysis. Finally, the contribution of testosterone’s aromatization within the dentate gyrus was assessed by local infusion of the aromatase inhibitor fadrozole, whose efficacy was confirmed by liquid chromatography-tandem mass spectrometry.

    Results

    Both hormones had antidepressant-like effects associated with a substantial overlap in transcriptional regulation, particularly in synaptic plasticity- and mitogen-activated protein kinase pathway-related genes. Further, chronic aromatase inhibition within the dentate gyrus blocked the protective effects of testosterone.

    Conclusions

    Both testosterone and estradiol exhibit anxiolytic- and antidepressant-like effects in gonadectomized male rats, while similarly regulating critical mediators of these behaviors, suggesting common underlying mechanisms. Accordingly, we demonstrated that testosterone’s protective effects are mediated, in part, by its aromatization in the dentate gyrus. These findings thus provide further insight into a role for estradiol in mediating the protective anxiolytic- and antidepressant-like effects of testosterone.

  10. #9
    Super Moderator Nelson Vergel's Avatar
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    A well written article that provides caution in decreasing estradiol too much.

    No longer viewed solely as a “female” sex steroid, the role of estrogen in muscle growth is undeniable. A multi-faceted growth agent, estrogen works hand in hand with testosterone to maximize many of the body’s key anabolic and anti-catabolic processes in a dose-dependent manner. Although science has yet to reveal the amount of estrogen required to maximize muscle hypertrophy, bodybuilders should be cautioned against the over-suppression of estrogen, as the evidence suggests that the current trend of maintaining estrogen levels within the low-normal range is unlikely to provide full muscle building benefits.

    http://www.ironmagazine.com/2015/mus...en-connection/

  11. #10
    Super Moderator Nelson Vergel's Avatar
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    Another study warns about low estrogen in men:

    "The study was presented at the Endocrine Society's 97th annual meeting this month. In addition to finding that higher levels of testosterone led to lower HDL, and that estrogen didn’t affect HDL, Yu’s team found that low levels of estrogen led to higher fasting blood sugar levels, worsening insulin resistance and increasing fat in muscles. The latter indicates developing diabetes, a risk factor for heart disease."

    Men’s Heart Disease Partly Due to Low Estrogen
    Last edited by Nelson Vergel; 11-12-2015 at 11:11 AM.

  12. #11
    Super Moderator Nelson Vergel's Avatar
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    SAT-237: High Aromatase Activity in Men with Low Testosterone Is Associated with Higher Spine BMD, Increased Truncal Fat Mass and Reduced Lean Mass


    Abstract:
    Background: Because the aromatase enzyme catalyzes the conversion of testosterone to estradiol, the activity of this enzyme could be important in the musculoskeletal health of men with low testosterone.
    Objective: To determine the influence of aromatase activity on the bone mineral density (BMD) and body composition of patients with low testosterone.
    Methods: The baseline data of ninety patients, between 40 to 74 years old, participating in a genetic study of response to testosterone therapy in men with low testosterone (i.e. <300 ng/dl) were analyzed. BMD and body composition were measured by dual energy x-ray absorptiometry. Serum testosterone was measured by automated immunoassay, estradiol by ultrasensitive enzyme immunoassay, and sex hormone binding globulin by enzyme immunoassay.
    Results: Men in the highest tertile of estradiol to testosterone ratio (E2/T) had the highest spine BMD (p=<0.048), highest truncal fat (p=0.046) and lowest total lean body mass (p=0.045). A similar pattern was observed in the upper extremities, i.e. fat mass significantly increased (p=0.047) while lean mass significantly decreased (p=0.034) with increasing E2/T tertiles.
    Conclusions: Our findings suggest that in men with low testosterone, aromatase activity could be an important determinant of musculoskeletal health. Men with high aromatase activity are able to maintain a higher BMD despite low circulating testosterone, but have lower lean and higher truncal fat mass compared to those with lower aromatase activity.
    Values are Means±SD, E2/T: estradiol to testosterone ratio, FEI: free estradiol index, FAI: free androgen index
    *p<0.05 tertile 1 vs. tertile 3.
    **p<0.05 tertile 2 vs. tertile 3.

  13. #12
    Super Moderator Nelson Vergel's Avatar
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    When using the sensitive estradiol test (liquid chromatography/ Mass spectrometry) :

    In men and postmenopausal women, the median concentrations of total estrogens (E1 + E2) were 39 and 22 pg/mL, and the median E2/E1 ratios were 0.98 and 0.55, respectively.

    Source: http://www.ncbi.nlm.nih.gov/pubmed/18343779
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  15. #14
    Super Moderator Nelson Vergel's Avatar
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    Jul 17, 2014 ... Estradiol is a hormone more abundant in women than men that is produced by the aromatization of testosterone in liver, fat and other cells.


    Why All Men Should be Tested with the Ultrasensitive Estradiol Test

    www.excelmale.com/showthread.php?1178-Why...Estradiol...

    This test is generally NOT suggested over the regular estradiol test (LC004515). The only difference between this test and the regular estradiol ...


    Why All Men Should be Tested with the Ultrasensitive Estradiol Test ...

    www.excelmale.com/showthread.php?1178-Why...Estradiol...

    This test is generally NOT suggested over the regular estradiol test (LC004515). The only difference between this test and the regular estradiol ...


    Estradiol: Ongoing Monitoring

    www.excelmale.com/showthread.php?3907-Estradiol-Ongoing...

    My estradiol rose from 14/sensitive prior to initiating TRT, to 22/sensitive at the three month mark, and 23/sensitive at the seven month mark.


    Q about low estradiol

    http://www.excelmale.com/showthread....9-Q-about-low-estradiol

    Q about low estradiol. My labs came back T was at 256 Free was 6.6 E2 was 6.6 ultrasensitive. LH 2.4 and FSH 1.5. So not good all ...


    Latest Blood Test Results - Free and Total Testosterone & Estradiol ...

    www.excelmale.com/showthread.php?3423-Latest...Estradiol...

    First Post - Testosterone, E2 and Anastrozole Hi Guys - first of all, I really appreciate this great forum & site. It has certainly educated me on TRT ...


    Role of Estradiol and Sex Hormone Binding Globulin in Men

    www.excelmale.com/showthread.php?3483-Role-of-Estradiol...

    It has been traditionally thought and believed that sex hormone binding globulin ( SHBG) is more or less correlated to estradiol (E) levels and ...


    High Estradiol Boosts Libido in Men on Testosterone Therapy

    www.excelmale.com/showthread.php?1666-High-Estradiol...in...

    633 Elevated serum estradiol is associated with increased libido in men receiving testosterone replacement therapy (TRT), according to ...


    Thread: Testosterone and estradiol in chronic pain- Potential use in ...

    www.excelmale.com/showthread.php?3938...and-estradiol-in...

    A novel use for testosterone to treat central sensitization of chronic pain in fibromyalgia patients Highlights •Testosterone is effective therapy for fibromyalgia .


    Low estradiol on HRT

    www.excelmale.com/showthread.php?3471-Low-estradiol-on-HRT

    I took the anastrazole at the beginning of the treatment and I realized after a couple of blood tests myestradiol was floored <3 to <5 (done at lab ...

    Estradiol vs ultra sensitive estradiol

    www.excelmale.com/showthread.php?3358-Estradiol-vs...estradiol

    At this rate on the basic estradiol test most guys are way over 50 or 60 which studies have always said is bad for prostate and sex drive.


    My estradiol labs experiment

    www.excelmale.com/showthread.php?3723-My-estradiol-labs...

    On April 22, 2015 I had blood drawn at my local men's health clinic for a " standard" estradiol test at 10:30 a.m. I then drove to a different lab and ...


    Estradiol Ultrasensitive First Results; OK?

    www.excelmale.com/showthread.php?3898-Estradiol...First...OK

    So the question is would there be any reason for me to consider anything else to limit or lower myestradiol or should I just check it again in a ...


    ExcelMale.com TRT, hCG,AI, Health Forums - Role of Estradiol in ...

    www.excelmale.com/content.php?143-Role-of-Estradiol-in...Its...

    Jul 28, 2014 ... The role of estradiol and anastrozole in men on testosterone replacement therapy By Nelson Vergel, BsChE, MBA Testosterone is the ...


    19 Year Old Blood Test Results (question about Estradiol)

    www.excelmale.com/showthread.php?3901-19-Year...Estradiol)

    Good afternoon ExcelMale, I was recently referred to this website by a fellow member of a lifting community via Facebook. A little background ...


    Hcg and estradiol questions

    www.excelmale.com/showthread.php?3069-Hcg-and-estradiol...

    My estradiol is 52 and my doc said that was high but he would worry until it gets past 71. This doesn't seem right to me. In terms of estradiol, ...


    New Labs- Adrenal Fatigue and Low Estradiol

    www.excelmale.com/showthread.php?3276-New-Labs...Estradiol

    My sensitive estradiol is still at 14, which hasn't changed since November, and my regular estradiol is at 29. I'm still battling adrenal fatigue and ...


    Danazol to increase free testosterone and decrease estradiol?

    www.excelmale.com/showthread.php?3406-Danazol...estradiol

    Danazol is antiestrogenic and weakly androgenic. Anyone include this in their protocol? Would this be used in place of Aremadex and ...


    High Estradiol, Not Testosterone, Found Elevated in Men with ...

    www.excelmale.com/showthread.php?3227-High-Estradiol...

    ... 10.1007/s12291-013-0411-3. Epub 2014 Jan 29. Serum Testosterone, 17β- Estradiol and PSA Levels in Subjects with Prostate Disorders.

    Estradiol and Therapeutic Management: What you should know – By ...

    www.excelmale.com/showthread.php?1992-Estradiol-and...

    Estradiol is simply a class of Estrogen of which there are about 30 different types. Estradiol (E2 or 17β-Estradiol, or as Oestradiol) is a.


    Testosterone, DHEA and Estradiol- Effect on Fat Mass in Men and ...

    www.excelmale.com/showthread.php?3181...and-Estradiol...

    1176 Higher estradiol was linked to higher visceral (deep belly) fat in men and women. High bioavailable testosterone was linked to higher ...


    Sustanon 250 vs Cypionate Which causes less increase in Estradiol?

    www.excelmale.com/showthread.php?3398...250-vs...Estradiol

    I am 70 and well aware of the risks for an old timer...my main concerns hematocrit and estradiol...I was planning to try 100-150 mg cypionate as ...


    Excellent Article on Risks of Low Estradiol and Aromatase Inhibitor ...

    www.excelmale.com/showthread.php?2784...on...Estradiol...

    Finally, a good article on estradiol and aromatase inhibitors!! "Truthfully, it is impossible to state whether anyone has been harmed by using ...


    Quest Diagnostics Ultrasensitive Estradiol Code

    www.excelmale.com/showthread.php?2024-Quest...Estradiol-Code

    The aforementioned thread by Nelson is a great post, emphasizing you MUST run the more sensitiveestradiol assay. The standard assay is not ...


    Estradiol question

    www.excelmale.com/showthread.php?3008-Estradiol-question

    I was always told to just go off of the sensitive estradiol test not the regular. I am doing another saliva test tomorrow, hopefully my dr will have a ...


    Low Testosterone and High Estradiol Linked to Sudden Cardiac Arrest

    www.excelmale.com/showthread.php?2520-Low...Estradiol...to...

    For First Time, Researchers Analyze Levels of Testosterone and Estradiol to Predict Patients' Likelihood of Suffering Usually Fatal Condition, ...


    High Estradiol Boosts Libido in Men on Testosterone Therapy - Page 2

    www.excelmale.com/showthread.php?1666-High-Estradiol...

    I have been warning men and clinics not to be so aggressive treating estradiol in men with the overuse of anastrozole. Here is a recent study ...


    Effect of a single injection of testosterone enanthate on 17β estradiol ...

    www.excelmale.com/showthread.php?2740...of...estradiol...

    It is interesting to see for the first time that some men do not have increases in estradiol after a shot of testosterone. 9 out of 21 were in this ...


    Estradiol of < 21.80 pg/ml and > 30.11 pg/ml resulted in greater ...

    www.excelmale.com/showthread.php?589-Estradiol-of...

    Circulating estradiol and mortality in men with systolic chronic heart failure. Source Center for Heart Disease, Cardiology Department, Military ...

    DHT Counteracts Estradiol's Beneficial Effect on Insulin Sensitivity

    www.excelmale.com/showthread.php?2609-DHT...Estradiol-s...

    By blocking testosterone, DHT and estradiol in different arms, this study could actually see the effect of each of these hormones on fat mass and ...


    Estradiol (standard vs. sensitive)

    www.excelmale.com/showthread.php?1845-Estradiol-(standard-vs...

    Hey guys: 2 months on TRT, just got some BW done. Wanted to get your feedback on my estradiol. Today: Total Test; 786 ng/dl (250 - 1100) ...


    Best time of day for Estradiol test?

    www.excelmale.com/showthread.php?2486-Best-time...Estradiol...

    My doctor has finally agreed to let me get the ultrasensitive estradiol test. I have been on TRT for 15 years +/-. Is there a certain time of day that ...


    advia centaur estradiol e2

    http://www.excelmale.com/showthread....advia-centaur-estradiol...

    Dear Nelson, My health provider finly agreed to provid me the information on the estradiol E2 test he uses : "The ADVIA Centaur Enhanced ...


    Low Free T & Estradiol - Thoughts?

    http://www.excelmale.com/showthread....43-Low-Free-T-Estradiol...

    Nelson suggested I move this thread to this area of the forum. Im im also going to get my FSH and LH tested. I've been reading this forum for the ...


    Can Marijuana Increase Estradiol and Man Boobs (Gynecomastia)?

    www.excelmale.com/showthread.php?1152-Can...Estradiol-and...

    Animal studies have shown that exposure to the active ingredient in marijuana can result in a decrease in testosterone levels, a reduction of ...


    Video: Estradiol may pose some risk in low-T supplementation

    www.excelmale.com/showthread.php?2294-Video-Estradiol...

    She only mentions it at the end and briefly. http://video.healio.com/video/Video- Estradiol-may-pose-some-r More on estradiol in men: ...


    Test to Estradiol ratios

    www.excelmale.com/showthread.php?1557-Test-to-Estradiol-ratios

    Endo had me start Clomid in November to see if I could get my body to make more T. Some labs - 11/11 - Test 271, Estradiol 29 - off all ...


    Hypopituitary, testosterone and estradiol.

    http://www.excelmale.com/showthread....-Hypopituitary...estradiol

    I respect Phil but I am not in agreement with his estradiol opinions. I believe you and most guys are overtreating with anastrozole. You may ...


    DHT Gel Shuts Down LH, FSH, Estradiol and T But Sustained ...

    www.excelmale.com/showthread.php?1869-DHT...Estradiol...

    Introduction Male sexual function is highly androgen dependent but whether aromatization of testosterone (T) to estradiol is required remains ...










  16. #15
    Super Moderator Nelson Vergel's Avatar
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    Effects of Aromatase Inhibition on Bone Mineral Density and Bone Turnover in Older Men with Low Testosterone Levels

    The Journal of Clinical Endocrinology & Metabolism
    Volume 94, Issue 12

    Context: Aging is associated with declining gonadal steroid production, low bone mineral density (BMD), and fragility fractures. The efficacy and safety of testosterone replacement in older men remains uncertain.

    Objective: The objective of the study was to assess the effects of aromatase inhibition on BMD in older men with low testosterone levels.

    Design and Setting: This was a 1-yr, double-blind, randomized, placebo-controlled trial that was conducted at a tertiary care academic center in Boston, MA.
    Participants: Participants included 69 men aged 60+ yr with borderline or low testosterone levels and hypogonadal symptoms.

    Intervention: Intervention included 1 mg anastrozole daily or placebo.

    Main Outcome Measures: Changes in gonadal steroid hormone levels, BMD, and bone turnover markers were measured.

    Results: Mean serum testosterone increased from 319 ± 93 ng/dl at baseline to 524±139 ng/dl at month 3 (P < 0.0001) and declined slightly to 474 ± 145 ng/dl by 1 yr. Estradiol levels decreased from 15 ± 4 pg/ml at baseline to 12 ± 4 pg/ml at month 3 and then remained stable (P< 0.0001). Posterior-anterior (PA) spine BMD decreased in the anastrozole group as compared with placebo (P = 0.0014). In the anastrozole group, PA spine BMD decreased from 1.121 ± 0.141 g/cm2 to 1.102 ± 0.138 g/cm2, whereas in the placebo group, PA spine BMD increased from 1.180 ± 0.145 g/cm2 to 1.189 ± 0.146 g/cm2. Qualitatively similar, but not statistically significant, changes occurred at the other sites. Bone turnover markers were not affected by anastrozole therapy.

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  20. #19
    Super Moderator Nelson Vergel's Avatar
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    Testosterone Needs Estrogen's Help to Inhibit Depression

    "Kabbaj’s latest paper was published in Biological Psychiatry.He already knew that testosterone had a protective effect on males, just as estrogen and progesterone do on females. He also knew that most testosterone was converted into estrogen in the brain. What he didn’t know was that those anxiety- and depression-inhibiting effects couldn’t be produced unless the testosterone was first converted to estrogen.
    “There is an enzyme in the brain that ‘mediates’ the conversion of testosterone into estrogen,” Kabbaj said. “We inhibited that enzyme in a specific brain area implicated in the regulation of mood. And when you do that, you lose the antidepressant effect of testosterone. So the conversion is very important.”
    His lab targeted the hippocampus area of the brain, where testosterone acts through what’s known as the MAPK pathway to induce its antidepressant and anti-anxiety effects.
    “But we have to be careful about that pathway,” Kabbaj said, “because it’s also implicated in cellular growth and cancer. Therefore, we’re looking for other pathways that don’t have these effects. It’s complicated. Nothing is ever simple, but we’ll get there.”

    http://news.fsu.edu/More-FSU-News/24...bit-depression

  21. #20
    Super Moderator Nelson Vergel's Avatar
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    Name:  estradiol brain effects.gif
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    "There are further experiments on rats that clarify how testosterone acts in the brain. If estradiol is injected into the hypothalamus of a castrated rat instead of testosterone, it works just as well in restoring normal intromission and ejaculation. If one injects DHT—a very potent androgen that cannot be converted to estradiol—no recovery is seen. These findings together suggest that, when testosterone enters the hypothalamus, it is converted to estradiol (by the enzyme aromatase), and estradiol then facilitates sexual behavior (Nelson, 2011). Consistent with this interpretation, both the enzyme aromatase and estrogen receptors are present in the hypothalamus. Furthermore, the administration of drugs that block the action of aromatase interferes with the behavioral effects of testosterone. Thus we can conclude that the conversion (or “aromatization”) of testosterone to estradiol is necessary for male sexual behavior in rats. So much for the notion that estrogens are “female” hormones."

    There is also some uncertainty about the importance of the aromatization process (the conversion of testosterone to estradiol in the brain) for human sexuality. There have been suggestions that testosterone acts directly on the brain in primates and does not require conversion to estradiol. Aromatization clearly does play some role, however. Aromatase-blocking drugs interfere with sexual activity in male monkeys, and men who are congenitally deficient in the aromatase enzyme have a low sex drive, which can be increased by the administration of estradiol. It seems most likely that the effects of testosterone on men's sexuality are partly direct (via androgen receptors) and partly indirect (via aromatization and estrogen receptors), but the differences between these two kinds of effects remain to be worked out."

    http://sites.sinauer.com/levay4e/webtopic05.04.html
    Last edited by Nelson Vergel; 10-02-2015 at 12:13 AM.

  22. #21
    Super Moderator Nelson Vergel's Avatar
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    Testosterone and Estrogen in Men: Good, Bad or Indifferent?

    Founder
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  23. #22
    Super Moderator Nelson Vergel's Avatar
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    Estrogen in Men: Best Review Paper

    Best review paper on the role of estrogen (estradiol in particular) in men and the use of anastrozole.
    Attached Images Attached Images

  24. #23
    Super Moderator Nelson Vergel's Avatar
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    Am J Respir Crit Care Med. 2015 Dec 10. [Epub ahead of print]

    Higher Estradiol and Lower Dehydroepiandrosterone-Sulfate Levels Are Associated With Pulmonary Arterial Hypertension in Men.

    Ventetuolo CE1, Baird GL2, Barr RG3, Bluemke DA4, Fritz JS5, Hill NS6, Klinger JR7, Lima JA8, Ouyang P9, Palevsky HI10, Palmisciano AJ11, Krishnan I12, Pinder D13, Preston IR14, Roberts KE15, Kawut SM16.



    Abstract

    RATIONALE:
    Recent studies have focused on the role of female sex and estradiol (E2) in pulmonary arterial hypertension (PAH), but it is not known whether sex hormones are risk factors for PAH in men.

    OBJECTIVES:
    We performed a case-control study to determine whether hormone levels (E2, dehydroepiandrosterone-sulfate [DHEA-S], and testosterone) are associated with PAH in men.

    METHODS:
    Plasma sex hormone levels in men with idiopathic, heritable, or connective tissue disease-associated PAH were compared to those from age- and body mass index-matched men without clinical cardiovascular disease.

    MEASUREMENTS AND MAIN RESULTS:
    There were 23 cases with PAH (70% had idiopathic PAH, 65% were functional class III/IV) and 67 controls. Higher E2 and E2:testosterone levels were associated with the risk of PAH (OR per 1 ln[E2:testosterone] = 6.0, 95% CI 2.2 - 16.4, p = 0.001) while higher levels of DHEA-S were associated with a reduced risk (OR per 1 ln[DHEA-S] = 0.1, 95% CI 0.0 - 0.3, p = 0.001). E2 and DHEA-S levels were strong predictors of case status (c-statistic for both 0.82) but testosterone was not (c-statistic 0.53). Higher levels of E2 were associated with shorter six-minute walk distances (p = 0.03) whereas higher levels of DHEA-S were associated with lower right atrial pressure (p = 0.02) and pulmonary vascular resistance (p = 0.01) in men with PAH.

    CONCLUSIONS:
    Higher levels of E2 and lower levels of DHEA-S were associated with PAH in men. Sex-based differences in sex hormone processing and signaling may contribute to unique phenotypes in pulmonary vascular disease.

  25. #24
    Super Moderator Nelson Vergel's Avatar
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    High Estradiol in Men Not Associated with ED

    Testosterone replacement improves quality of life and is aromatized in men in adipose tissues to estrogen. Hyperestrogenism is believed to be harmful to male sexuality. This is a description of our experience of screening 34,016 men in the Low T Centers, of which approximately 50% were converted to treatment. Men were treated with injectable testosterone, and we have available data from 2009 to 2014.


    The data were extracted from our electronic health record (AdvancedMD) of 35 Low T Centers across the United States. In all, 7,215 (20.2%) out of the 34,016 patients had high estradiol levels defined as >/=42.6 pg/ml. Estradiol was measured using electro-chemiluminescence immunoassay.


    Of the patients who had high estradiol levels, the age distribution was as follows: 132/989 (13.3%) were older than 65 years, 3,753/16,955 (22.1%) were between 45 and 65 years; 2,968/15,857 (18.7%) were between 25 and 44 years, 7/215 (3.3%) were younger than 25 years. The difference between extreme age groups (<25 and >/=65) was statistically significant using a chi-square test (p = .013). The correlation coefficient of serum estradiol to age was .53, SD = 8.21.


    It was observed that practitioners used aromatase inhibitor and selective estrogen receptor modulator to treat symptoms of hyperestrogenism, irrespective of blood estradiol levels. Gynecomastia was rarely documented as a reason for the prescription.


    OUR FINDING WAS THAT HIGH ESTRADIOL LEVELS WERE NOT ASSOCIATED WITH HIGHER RATES OF LOW LIBIDO BUT ESTABLISHED HIGHER RATES OF DOCUMENTED LOW LIBIDO WITH THOSE WITH NORMAL OR LOWER ESTRADIOL LEVELS. The difference was statistically significant (p < .05).


    Tan RS, Cook KR, Reilly WG. High estrogen in men after injectable testosterone therapy: the low T experience. Am J Mens Health 2015;9(3):229-34.http://jmh.sagepub.com/content/9/3/229.abstract

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  29. #28
    Super Moderator Nelson Vergel's Avatar
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    Estradiol in Men: Friend or Enemy?

    Allison Woodworth from www.PrimeBody.com reviews data on estradiol in men and discusses the use of anastrozole to manage it. She stresses the need for proper blood testing and management.

  30. #29
    Super Moderator Nelson Vergel's Avatar
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    This study used a high dose of 1 mg per day of anastrozole.

    Aromatase Inhibition Reduces Insulin Sensitivity in Healthy Men -

    http://press.endocrine.org/doi/pdf/10.1210/jc.2015-4146

  31. #30
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    Estradiol blunts muscle damage induced by exercise






    GO TO PAGE 2 OF THIS THREAD BY CLICKING ON THE NUMBER TWO BELOW (BOTTOM RIGHT HAND CORNER)
    Last edited by Nelson Vergel; 09-22-2016 at 12:19 AM.

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