Low total Testosterone, low free Testosterone, and low SHBG associated with increased CRP. Serum total estradiol and free estradiol trended to a positive association, but did not reach statistical significance.
total and bioavailable Estradiol associated with increased hsCRP in men age 40-80. Bioavailable is calculated with serum calculated free Testosterone and albumin bound Testosterone.
Estradiol found to be associated with increased IL-6 in older men. This after, the adjustments to exclude variables. Other inflammatory markers were not associated.
modest statistically significant inverse associations for total and calculated free testosterone, and modest positive associations for total and calculated free estradiol with CRP concentration
Estradiol concentrations were also weakly positively associated with WBC count
An association between testosterone and WBC count was not observed
These findings are consistent with the hypothesis that in men higher androgen concentration is anti-inflammatory, and higher estrogen concentration is pro-inflammatory.
the probability of elevated CRP concentrations (≥ 3 mg/L) decreased with higher total and calculated free testosterone concentrations, while the probability increased with higher total and calculated free estradiol concentrations
there is ample evidence supporting the immunosuppressive effect of androgens
The incidence of autoimmune diseases is higher in androgen-deficient men
Studies have shown that the induction of hypogonadism in older men is followed by a significant increase in IL-6 concentrations (Khosla et al. 2002), a potent stimulator of inflammation, and that activation of the androgen receptor exerts a direct anti-inflammatory effect
It has been suggested that the mechanisms for the immunosuppressive effect of androgens could be either a direct effect on the expression of inflammatory genes (Bellido et al. 1995; Asirvatham et al. 2006), or an indirect effect through inhibition of nuclear factor-kB activation
Estradiol is the major biologically active estrogen, and about 80% is formed in adult men from the aromatization of testosterone primarily in the adipose tissue
estrogen can stimulate the transcription factor C/EBP-β, which is involved in CRP transcription
Most prior cross-sectional studies have observed inverse associations between androgen concentrations and inflammatory biomarkers
A recent study in Chinese men showed that lower concentrations of total and calculated free testosterone were associated with higher CRP concentration
Data from the Boston Area Community Health Survey also reported inverse associations between testosterone and CRP concentrations
The first trial found a decrease in CRP, interleukin-1β (IL-1β), and tumor necrosis factor-α (TNFα) but no changes in IL-6 and IL-10 concentrations between the active treatment and placebo arms
the majority of studies in the literature have not observed statistically significant associations between estradiol and inflammatory biomarkers in men, although several of them observed point estimates in the positive direction
total testosterone and estradiol compete for binding to SHBG, and seem to have opposite effects on the concentration of inflammatory biomarkers
A small randomized controlled trial of estrogen replacement therapy in prostate cancer patients showed an increase in CRP in the active treatment group versus the comparator group
Obese men are known to have lower androgen concentrations compared to their normal-weight counterparts
The strongest suggestion of an interaction was the inverse association between androstanediol glucuronide and CRP concentrations in obese participants, while the association was positive in the non-obese
A recent Chinese cross-sectional study observed stronger inverse associations between total testosterone and CRP concentrations in individuals with a BMI of 27.5 kg/m2 or greater
our results suggest that total and calculated free testosterone are modestly inversely associated with CRP concentrations, and that total and calculated free estradiol are modestly positively associated with CRP and WBC
Study results suggest that higher Testosterone and lower Estrogen levels provide anti-inflammatory effects in men. The inflammatory biomarker assessed here was CRP. Low total and calculated free Testosterone was associated with an increase in CRP. In contrast, total and free Estrogen was associated with an increase in CRP. Estradiol increased WBC count and SHBG was inversely related to WBC count in this study.
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
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.
Higher Testosterone and DHT levels in men was found to be positively associated with FEV1 and FVC; Estradiol was not. The question here is cause or effect.
Also interesting is the fact that smokers had higher Testosterone levels compared to non-smokers.
Time that physicians start following the science. Study using data from the Multi-ethnic Study of Atherosclerosis was used to assess hormones and fatty liver in men and women. Increasing bioavailable Testosterone levels in women was found to be associated with increasing fatty liver in post-menopausal women. The opposite was found to be true in men. Higher Estradiol levels were found to be associated with increased fatty liver in both sexes. However, the statistical significance was higher with men. Higher SHBG was associated with lower fatty liver incidence in men.
Study finds that low free T and low Total T were associated with decline in desire, ED and activity versus none with Estradiol and SHBG in older men. The difficult issue is the threshold of "low T". The definition of "low T" is not uniform and varies with age. Thus baseline evaluations and correlation with symptoms, metabolic dysfunction must be done.
Study finds increased risk of sudden MI in men with low Testosterone and elevated Estradiol. In converse, increased risk is associated with elevated Estradiol in women.
animal model finds that high fat diet induces ED more through increased Estradiol production than low Testosterone. Of course the authors focused on the drugs to block E2 once produced, rather then reducing the T to E2 aromatase activity. This metabolic syndrome model implies that increased aromatase activity will be present.
Study points to association of low Estradiol and spermatogenesis in males in infertile couples. The authors eluded to the association of low Estradiol with low Testosterone, and BMI which is the likely etiology. Low BMI will result in low aromatase activity. For men, the majority of Estradiol production occurs from Testosterone via aromatase activity. Estradiol likely exists in a "U" shaped pattern of benefit: to low hinders optimal physiologic function and contributes to inflammation and disease in men.
small cohort with low serum Total Testosterone improved T:E2 ratio with clomid. Clomid restores the HPA through inhibition of the negative feedback of Estradiol on the Hypothalamus and Pituitary in men. This allows for an increase in gonadotropin production and thus increase in testosterone production. Aromatase inhibition therapy would likely still prove beneficial in this situation.
from CHAMP study: low serum Testosterone, free Testosterone, Estradiol and Estrone associated with functional decline in elderly men via muscle weakness.
Again, Testosterone and here Estradiol are merely there for libido and sex. What tunnel vision?! What about hsCRP? What about fibrinogen? What about IL-1beta? What about TNF-alpha? These inflammatory cytokines have all been reported to elevate as a result of estrogen production in men.
And PSA? No mention of it here.
This linear, tunnel vision thinking on hormones has got to stop!
The study points out that all clients were using AIs and SERMs irregardless of whether they had elevated estrogens or not. That is not a well designed study. One group should have had AI's if elevated estrogens were present and another group should not--this would compare the effects of aromatase activity. Second, this was simply a retrospective chart review. Third, a 50% conversion of 34,000 + men is very high when you look at the literature. Fourth, they point to gynecomastia as a means of negative? The cardiovascular implications are more significant. These studies just seem to focus on superficial things. Fifth, did libido problems exist before? What were the free levels?
This falls in the paucity of data (2 studies) that point to excessive lowering of estradiol effecting libido and sexual performance.