a case report of anti-HCG antibodies in a 22 year old male on HCG therapy for idiopathic hypothalamic hypogonadism. the Result was an autoimmune hypothyroidism as a result of the anti-HCG.
Those with Alzheimer's disease have associated dysfunction of glucose metabolism in the brain, particularly in the hippocampus. It has been reported that a ketogenic diet can improve cognitive function in these individuals. In this study, the ketone bodies were initiated through a diet high in medium chain fatty acids. The ketone bodies served as an alternative fuel source for the brain.
There are alot of problems with evidence-based medicine. Don't for one minute think that a "study" can be without major flaws and biases. In fact, alot of the studies reported by the press are based on poorly designed and manipulated studies. Probably 50% of the studies that I read I disgard after evaluating the study design and statistics.
report of 2 cases studies that find link between autism and gastrointestinal inflammation. Again, suggestion some immune system dysfunction in the gastrointestinal system in some children with autism
I look forward to the published results of this study as this abstract references the WHI as the "same entry" criteria. I imagine the HRT would be the same too, but will wait to see. There is a serious problem with proper reporting of synthetic estrogens as bioidentical estrogens and synthetic progestins as bioidentical progesterone; Also, what is the dosage. Most individuals are massively overdosed. This study was said to be a "landmark". Could just be don't use synthetic hormones: which is what the WHI said.
in vitro studies had shown that the progesterone metabolites, 5α-dihydroprogesterone (5αP) and 3α-dihydroprogesterone (3αHP), respectively, exhibit procancer and anticancer effects on receptor-negative human breast cell lines
Onset and growth of ER/PR-negative human breast cell tumors were significantly stimulated by 5αP and inhibited by 3αHP
When both hormones were applied simultaneously, the stimulatory effects of 5αP were abrogated by the inhibitory effects of 3αHP and vice versa
Treatment with 3αHP subsequent to 5αP-induced tumor initiation resulted in suppression of further tumorigenesis and regression of existing tumors
Tumorigenesis of ER/PR-negative breast cells is significantly enhanced by 5αP and suppressed by 3αHP, the outcome depending on the relative concentrations of these two hormones in the microenvironment in the breast regions
The findings show that the production of 5αP greatly exceeds that of 3αHP in ER/PR-negative tumors and that treatment with 3αHP can effectively block tumorigenesis and cause existing tumors to regress
hypothesis that a high 3αHP-to-5αP concentration ratio in the microenvironment may foster normalcy in noncancerous breast regions.
a large proportion (about 30% to 60%) of breast tumors are ER and/or PR negative
about 90% of normal proliferating breast epithelial cells are receptor negative
Our previous in vitro studies had shown that breast tissues and cell lines readily convert progesterone to 5α-pregnanes, such as 5αP, and delta-4-pregnenes, such as 3αHP (Figure (Figure1),1), and that tumorous breast tissues [15] and tumorigenic breast cell lines [16] produce higher levels of 5αP and lower levels of 3αHP than do normal breast tissues and nontumorigenic cell lines
The progesterone metabolism studies suggested that increases in 5αP and decreases in 3αHP production accompany the shift toward breast cell neoplasia and tumorigenicity
In vitro studies on five different human breast cell lines showed that cell proliferation and detachment are significantly increased by 5αP and decreased by 3αHP
the prevailing theory of hormonal regulation of breast cancer, as well as hormone-based therapies, revolves around estrogen and/or progesterone and ER/PR-positive breast cells and tumors.
Not only do these "receptor-negative" breast cancers fail to benefit from current hormonal therapies, but they also generally exhibit more-aggressive biologic behaviors and poorer prognosis than the receptor-positive ones
The results of the studies reported here show for the first time that the progesterone metabolites, 5αP and 3αHP, act as hormones that regulate ER/PR-negative breast tumor formation, growth, and regression
The onset of the ER/PR-negative human breast cell tumors in mice was considerably accelerated, and the growth significantly stimulated, by just one or two applications of 5αP
In contrast, 3αHP retarded onset of tumor formation, suppressed tumor growth, and inhibited or regressed existing 5αP-induced tumors
When both hormones were administered simultaneously, the effects of one were abrogated by the effects of the other.
The 5αPR and 3αHPR (which are associated with the plasma membranes of both ER/PR-positive [19] and ER/PR-negative [29] cells) are distinct from each other and from known ER, PR, androgen, and corticosteroid receptors, and lack affinity for other steroids, such as progesterone, estrogen, androgens, corticosteroids, and other progesterone metabolites
Levels of 5αPR are upregulated by 5αP itself and estradiol, and downregulated by 3αHP in both ER/PR-positive and -negative cells
ndications are that 5αP acts via the surface receptor-linked mitogen-activated protein kinase (MAPK; Erk1/2) pathway; 5αP significantly stimulates activation of Erk1/2 [30], increases the Bcl-2/Bax expression ratio [18] and actin depolymerization [31], and decreases expression of actin and adhesion plaque-associated vinculin [31], resulting in decreased apoptosis and increased mitosis and cell detachment
3αHP appears to suppress protein kinase C (PKC), phospholipase C (PLC), Ca2+ mobilization (unpublished observations), and the Bcl-2/Bax expression ratio [18], and increases expression of the cell-cycle inhibitor p21 [18], resulting in increased apoptosis and decreased proliferation and detachment of breast cell lines.
serum from mice with tumors had significantly more 5αP than 3αHP
the tumors, which on average had about threefold higher concentrations of 5αP than the respective sera, and >10-fold higher 5αP than 3αHP levels
Previous in vitro metabolism studies showed that human breast tumor tissues convert significantly more progesterone to 5α-pregnanes like 5αP and less to 4-pregnenes like 3αHP than do paired normal (nontumorous) tissues
Similar differences in progesterone metabolism and enzyme gene expressions were observed between tumorigenic and nontumorigenic breast cell lines
breast carcinomas are able to synthesize progesterone
The current findings, along with the previous in vitro studies, suggest that the relative concentrations of 5αP and 3αHP in the breast microenvironment constitute important autocrine/paracrine determinants not only for tumorigenesis but also for potential regression of tumors and the maintenance of normalcy of ER/PR-negative breast cells/tissues.
Evidence presented here shows that a high concentration of 5αP, relative to 3αHP in the microenvironment, promotes initiation and growth of tumors, whereas a higher concentration of 3αHP, relative to 5αP, suppresses tumorigenesis and promotes normalcy
5α-reductase and 5αPR levels are upregulated by 5αP
in the 3αHP-treated mice, the elevated 3αHP levels, relative to 5αP, in the microenvironment could have opposed progression to xenograft neoplasia by its inherent anticancer actions and the suppression of 5αP synthesis and 5αPR expression
the opposing actions of the progesterone metabolites also appear to exert some control over the estrogen-regulated effects on breast cancer by their ability to modulate ER numbers in ER-positive cells
because both ER/PR-negative and ER/PR-positive, as well as normal and tumorigenic human breast cell lines, have been shown to respond to 5αP and 3αHP in vitro, it is suggested that these endogenously produced progesterone metabolites may also play regulatory hormonal roles in ER/PR-positive breast cancers, as well as in the maintenance of normalcy in nontumorous breast tissues.
The in vivo data provide further evidence that progesterone metabolites, such as 5αP and 3αHP, deserve to be considered as active hormones in their own right, rather than inactive waste products
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
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
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
BCAA improve NH3 metabolism. This is via muscle metabolism as reported in other studies. This study highlighted the differences in BCAA supplementation. One caveat is that high glutamine is the result from glutamate and this can increase hepatic encephalopathy.
nice review of some of the problems associated with a high fat ,high protein diet. These effects are seen in those utilizing long term dietary patterns of high protein and high fat intake.
Life extesnsions rebuttal to recent JAMA study. There was several significant flaws in that study and thus limited evidence can be gained by that study. In fact, I find no useful clinical information from that study.
In the rebuttal, there are flaws. The reference the low serum T after treatment and correctly discuss aromatase activity. But they fail the mention that the less than optimal serum T is likely the result of the high aromatase activity in these men. Age, stress, and weight are primary causes of increases estrogen production in these men. These would be why likely high estrogen production occurred and less than optimal serum T resulted. And, increased E2 will cause an increase in CRP which can precipitate CVD events.
Low endogenous bioavailable testosterone levels have been shown to be associated with higher rates
of all‐cause and cardiovascular‐related mortality.39,41,46–47 Patients suffering from CAD,13–18 CHF,137 T2DM,25–26 and obesity27–28
have all been shown to have lower levels of endogenous testosterone compared with those in healthy controls. In addition,
the severity of CAD15,17,29–30 and CHF137 correlates with the degree of testosterone deficiency
In patients with CHF, testosterone replacement therapy has been shown to significantly improve exercise tolerance while having
no effect on LVEF
testosterone therapy causes a shift in the skeletal muscle of CHF patients toward a higher concentration
of type I muscle fibers
Testosterone replacement therapy has also been shown to improve the homeostatic model of insulin resistance and hemoglobin
A1c in diabetics26,68–69 and to lower the BMI in obese patients.
Lower levels of endogenous testosterone have been associated with longer duration of the QTc
interval
testosterone replacement has been shown to shorten the QTc interval
negative correlation has been demonstrated between endogenous testosterone levels and IMT of the carotid arteries,
abdominal aorta, and thoracic aorta
These findings suggest that men with lower levels of endogenous testosterone may be at a higher risk of developing atherosclerosis.
Current guidelines from the Endocrine Society make no recommendations on whether patients with heart
disease should be screened for hypogonadism and do not recommend supplementing patients with heart disease to improve survival.
The Massachusetts Male Aging Study also projects ≈481 000 new cases of hypogonadism annually in US men within the same age
group
since 1993 prescriptions for testosterone, regardless of the formulation, have increased nearly 500%
Testosterone levels are lower in patients with chronic illnesses
such as end‐stage renal disease, human immunodeficiency virus, chronic obstructive pulmonary disease, type 2 diabetes mellitus
(T2DM), obesity, and several genetic conditions such as Klinefelter syndrome
A growing body of evidence suggests that men with lower levels of endogenous testosterone are more prone to develop CAD during
their lifetimes
There are 2 major potential confounding factors that the older studies generally failed to account for. These factors are
the subfraction of testosterone used to perform the analysis and the method used to account for subclinical CAD.
The biologically inactive form of testosterone is tightly bound to SHBG and is therefore unable to bind to androgen receptors
The biologically inactive fraction of testosterone comprises nearly 68% of the total testosterone in human serum
The biologically active subfraction of testosterone, also referred to as bioavailable testosterone, is either loosely bound
to albumin or circulates freely in the blood, the latter referred to as free testosterone
It is estimated that ≈30% of total serum testosterone is bound to albumin, whereas the remaining 1% to 3% circulates as free
testosterone
it can be argued that using the biologically active
form of testosterone to evaluate the association with CAD will produce the most reliable results
English et al14 found statistically significant lower levels of bioavailable testosterone, free testosterone, and free androgen index in
patients with catheterization‐proven CAD compared with controls with normal coronary arteries
patients with catheterization‐proven CAD had statistically significant lower levels of bioavailable
testosterone
In conclusion, existing evidence suggests that men with CAD have lower levels of endogenous testosterone,13–18 and more specifically lower levels of bioavailable testosterone
low testosterone levels are associated with risk factors for CAD such as T2DM25–26 and obesity
In a meta‐analysis of these 7 population‐based studies, Araujo et al41 showed a trend toward increased cardiovascular mortality associated with lower levels of total testosterone, but statistical
significance was not achieved (RR, 1.25
the authors showed that a decrease of 2.1 standard deviations in levels of total testosterone was associated
with a 25% increase in the risk of cardiovascular mortality
the relative risk of all‐cause mortality in men
with lower levels of total testosterone was calculated to be 1.35
higher risk of cardiovascular mortality is associated with lower levels of bioavailable testosterone
Existing evidence seems to suggest that lower levels of endogenous testosterone are associated with higher rates of all‐cause
mortality and cardiovascular mortality
studies have shown that lower levels of endogenous bioavailable testosterone are associated with higher rates
of all‐cause and cardiovascular mortality
It may be possible that using bioavailable testosterone to perform mortality analysis will yield more accurate results because
it prevents the biologically inactive subfraction of testosterone from playing a potential confounding role in the analysis
The earliest published material
on this matter dates to the late 1930s
the concept that testosterone replacement therapy improves angina has yet to be proven wrong
In more
recent studies, 3 randomized, placebo‐controlled trials demonstrated that administration of testosterone improves myocardial
ischemia in men with CAD
The improvement in myocardial ischemia was shown to occur in response to both acute and chronic
testosterone therapy and seemed to be independent of whether an intravenous or transdermal formulation of testosterone was
used.
testosterone had no effect on endothelial nitric oxide activity
There is growing evidence from in
vivo animal models and in vitro models that testosterone induces coronary vasodilation by modulating the activity of ion channels,
such as potassium and calcium channels, on the surface of vascular smooth muscle cells
Experimental studies suggest that
the most likely mechanism of action for testosterone on vascular smooth muscle cells is via modulation of action of non‐ATP‐sensitive
potassium ion channels, calcium‐activated potassium ion channels, voltage‐sensitive potassium ion channels, and finally L‐type
calcium ion channels
Corona et al confirmed those results by demonstrating that not only total testosterone levels are lower among diabetics,
but also the levels of free testosterone and SHBG are lower in diabetic patients
Laaksonen et al65 followed 702 Finnish men for 11 years and demonstrated that men in the lowest quartile of total testosterone, free testosterone,
and SHBG were more likely to develop T2DM and metabolic syndrome.
Vikan et al followed 1454 Swedish men for 11
years and discovered that men in the highest quartile of total testosterone were significantly less likely to develop T2DM
authors demonstrated a statistically significant increase in the incidence of T2DM in subjects receiving gonadotropin‐releasing
hormone antagonist therapy. In addition, a significant increase in the rate of myocardial infarction, stroke, sudden cardiac
death, and development of cardiovascular disease was noted in patients receiving antiandrogen therapy.67
Several authors have demonstrated
that the administration of testosterone in diabetic men improves the homeostatic model of insulin resistance, hemoglobin A1c,
and fasting plasma glucose
Existing evidence strongly suggests that the levels of total and free testosterone are lower among diabetic patients compared
with those in nondiabetics
insulin seems to be acting as a stimulant for the hypothalamus to secret gonadotropin‐releasing
hormone, which consequently results in increased testosterone production. It can be argued that decreased stimulation of the
hypothalamus in diabetics secondary to insulin deficiency could result in hypogonadotropic hypogonadism
BMI has been shown to be inversely associated with testosterone levels
This interaction may be a result
of the promotion of lipolysis in abdominal adipose tissue by testosterone, which may in turn cause reduced abdominal adiposity.
On the other hand, given that adipose tissue has a higher concentration of the enzyme aromatase, it could be that increased
adipose tissue results in more testosterone being converted to estrogen, thereby causing hypogonadism. Third, increased abdominal
obesity may cause reduced testosterone secretion by negatively affecting the hypothalamus‐pituitary‐testicular axis. Finally,
testosterone may be the key factor in activating the enzyme 11‐hydroxysteroid dehydrogenase in adipose tissue, which transforms
glucocorticoids into their inactive form.
increasing age may alter the association between testosterone and CRP. Another possible explanation
for the association between testosterone level and CRP is central obesity and waist circumference
Bai et al
have provided convincing evidence that testosterone might be able to shorten the QTc interval by augmenting the activity of
slowly activating delayed rectifier potassium channels while simultaneously slowing the activity of L‐type calcium channels
consistent evidence
that supplemental testosterone shortens the QTc interval.
Intima‐media thickness (IMT) of the carotid artery is considered a marker for preclinical atherosclerosis
Studies have shown that levels of endogenous testosterone are inversely
associated with IMT of the carotid artery,126–128,32,129–130 as well as both the thoracic134 and the abdominal aorta
1 study has demonstrated that lower levels of free testosterone are associated with accelerated progression
of carotid artery IMT
another study has reported that decreased levels of total and bioavailable testosterone are associated with progression
of atherosclerosis in the abdominal aorta
These findings suggest that normal physiologic testosterone levels may help to protect men from the development of atherosclerosis
Czesla et al successfully demonstrated that the muscle specimens that were exposed to metenolone had a significant shift
in their composition toward type I muscle fibers
Type I muscle fibers, also known as slow‐twitch or oxidative fibers, are
associated with enhanced strength and physical capability
It has been shown
that those with advanced CHF have a higher percentage of type II muscle fibers, based on muscle biopsy
Studies have
shown that men with CHF suffer from reduced levels of total and free testosterone.137 It has also been shown that reduced testosterone levels in men with CHF portends a poor prognosis and is associated with
increased CHF mortality.138 Reduced testosterone has also been shown to correlate negatively with exercise capacity in CHF patients.
Testosterone replacement therapy has been shown to significantly improve exercise capacity, without affecting LVEF
the results of the 3 meta‐analyses seem to indicate that testosterone replacement therapy does not cause an increase
in the rate of adverse cardiovascular events
Data from 3 meta‐analyses seem to contradict the commonly
held belief that testosterone administration may increase the risk of developing prostate cancer
One meta‐analysis reported
an increase in all prostate‐related adverse events with testosterone administration.146 However, when each prostate‐related event, including prostate cancer and a rise in PSA, was analyzed separately, no differences
were observed between the testosterone group and the placebo group
the existing data from the 3 meta‐analyses seem to indicate that testosterone replacement therapy does not increase
the risk of adverse cardiovascular events
the authors correctly
point out the weaknesses of their study which include retrospective study design and lack of randomization, small sample size
at extremes of follow‐up, lack of outcome validation by chart review and poor generalizability of the results given that only
male veterans with CAD were included in this study
the studies that failed to find an association
between testosterone and CRP used an older population group
low testosterone may influence the severity of CAD by adversely affecting
the mediators of the inflammatory response such as high‐sensitivity C‐reactive protein, interleukin‐6, and tumor necrosis
factor–α
Good review of Testosterone and CHD. Low T is associated with increased all cause mortality and cardiovascular mortality, CAD, CHF, type II diabetes, obesity, increased IMT, increased severity of CAD and CHF. Testosterone replacement in men with low T has been shown to improve exercise tolerance in CHF, improve insulin resistance, improve HgbA1c and lower BMI in the obese.
Study was undertaken in China due to alarming increase in breast cancer in Chinese women. This meta-analysis of 36 articles found a 44% increase in breast cancer with one abortion. This increased to 76% at 2 and 89% at 3 abortions respectively.
This study is very important and previous criticisms of prior studies linking abortion to breast cancer has been reporting bias. In China, due to the one child policy, abortion is a way of life and there is no cultural shame involved.
Truly horrifying statistic not reported anywhere. Hospital care has been associated with > 400,000 deaths annually. The third leading cause of death is medical therapies/treatments.
Here is where science and particularly conclusions fail the public. The authors conclusions are that tadalifl improves ED and sexual function irrespective of Testosterone levels. However, the results say something different. The group with normal Testosterone responded better versus the low Testosterone group. This difference didn't reach statistical significance though. This lack of statistical significance does not exclude the fact that there indeed was a difference. The authors conlcusions take no part in reporting the whole truth, just that which supports their hypothesis. The diagnosis of low T in this study was < 300 ng/dl
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.
Observational study finds BMI increase of 0.375 in both men and women per year. The waist circumference also increased by 0.37% per year in women compared to 0.27% in men. There was a significant reduction in physical activity over the same time period. In women, the reporting of physical inactivity increased to 52% FROM 19% compared to 44% FROM 11% in men. The authors found no association with change in calories. However, an assessment in quality of calories would have likely shown a glaring difference. Clear causation can not be concluded due to the fact that the study was observational.