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Testosterone Benefits, HRT for men

HRT men, Testosterone Benefits--3 pages   (3/6/16) http://healthfully.org/rc/id7.html

 

The state of medical science is worse than imagined.  For exposes on bad pharma read, Marketing Science, Side Effects, and Junk treatments . Testosterone (TTT) usage has come under attack by pharma and the FDA for the sake of pharma profits.  The FDA issued a black-box warning for TTT exposure of children by contact with a user.[1]   Pharma’s attacks TTT (which is not patented) for causing aggressive prostate cancer and Cardio-Vascular Disease (CDV); both are not just false, the opposite is true--see next page. [2] The testicles produce 95% of the TTT, about 5 mg/day & about 50 to 100 mcg of dihydrotestosterone (DHT) and estradiol.  In women TTT is synthesized by the corpus luteum (adjacent to the ovaries) and the adrenal cortex--TTT’s level is about 1/7th of a man’s, and it is more bioactive.  TTT is 60% bonded to a plasma protein, 38% to albumin, and 2% free.  DHT and TTT are androgens and thus build muscle mass.  DHT is 3-5 times more potent than testosterone or other androgens (except in skeletal muscle tissue, where testosterone is the main androgen). TTT & DHT freely enters target cells and binds to intracellular receptors which then bind to DNA promoting gene transcription.  DHT is more active at these sites.  DHT is necessary in early development for enlargement of the prostate, penis, and hair growth at the time of puberty.  The pituitary gland secretes LH and FSH; they act on the testes to stimulate the production of sperm and TTT.  Estrogen (estradiol) is a vital component of the male physiology, and in fact is made from TTT.  Estrogen decreases LH production and thus TTT.   The normal range for TTT is 13 - 40 nmol/L (370 - 1100 ng/dL), and for estradiol is 55 -165 pmol (10 - 30 ng/dL)--the first is the high levels for 80-year old man followed high level for a 20-year old.  Although, this doesn't automatically mean that a young man with 380 ng/dL has the same amount of testosterone of an 80+ year old, since there is usually a big difference in SHBG levels in the bloodstream between young and elderly, resulting in a much higher free testosterone level in the young. …” Wiki, and bioactivity of TTT is more. Normal TTT has declined over30% in the last 100 years, reason unknown—JK guess is hormone mimics possible from soy products whose usage has steadily increased since 1900.    

Noticeable improvements with topical testosterone, timeline to significant improvement—(Eur J Endocrinol. 2011, Nov. 675-85)

Sexual interest                     6 weeks                 Erection/ejaculation                  26 weeks                                                                                         Quality of life                        4+ weeks               Depressed mood                                       30 weeks    Erythropoiesis-red cells   52 weeks                                Lipid profile                         52 weeks                                Insulin sensitivity                        52 weeks    Muscle strength                16 weeks                               Reduced fat mass                16 weeks                                Reduced inflammation              12 weeks                                                                                                    Bone mass detectable at 26 weeks (versus gradual erosion, prevents osteoporosis).  Same benefits findings at.



[1] TTT is made both by girls and boys, pre-puberty.  The FDA used 8 cases of reported aggression or early genitalia enlargement as the reason for the black-box warning; just that their father took TTT supplement.  There was no laboratory investigation of the children to prove that those events were caused by contact with their father, rather than natural precocious puberty.        

[2] Pharma does marketing science to “show” e.g. that TTT doesn’t prevent CVD, insulin resistance, etc. by using too low a dose of TTT.  For example a Mayo Clinic study used “transdermal testosterone patch (50 mg per day; D-TRANS, by Alza (J&J).  The 2 lead authors were opinion leaders for 5 pharma companies.  JK, age 72, applies 150 mg TTT cream.  Androgel 1.62, 2 pumps (30 days) = 40.5 mg/day for ~$420.  When TTT therapy became popular, pharma attacked its usage.  Trials that don’t obtain a serum level of 580 ng/dL have not produced a TTT level comparable to that of a 60 year old in 1920—see JECM 2007 –thus won’t show full benefits.

 

Cognitive Function:  “Several observations suggest that testosterone is also capable of modulating neural systems in adult animals. For example, androgen treatment prevents N-methyl- D-aspartate (NMDA) excite-toxicity in hippocampal neurons12 and may facilitate recovery after injury by promoting fiber outgrowth and sprouting.13   Administration of TTT increases nerve growth factor (NGF) levels in the hippocampus, and induces an upregulation of NGF receptors in the forebrain.  TTT was protective of human primary neurons in culture, providing the most direct evidence for neuro-protective effects of TTT on human neural tissue”(Moffat), widely supported.  Equivocal finding are because of the study’s design.  TTT reduces the rate of age-related cognitive decline.

 

Alzheimer’s (AD) and Parkinson’s Diseases:  Beta amyloid accumulation in the brain is the physical manifestation for AD.  TTT decreases amyloid secretion from rat cortical neurons15 and reduces amyloid-induced neurotoxicity in cultured hippocampal neurons”16 Moffat.  TTT reduces neuronal secretion of Alzheimer's β-amyloid [Aβ] peptides.”  Based on in vitro study a decrease in Aβ release was observed.  “[L]long-term testosterone concentrations in individuals prior to the diagnosis of dementia.… The results of this study revealed an approximate 10% reduction in the risk for AD for each unit increase in free testosterone. Moffat; a 26% decrease for each 10-nmol FTI increase.  at and, at, and. Method through Modifying APOE genotype and BRACE1. Parkinson’s Disease, TTT improves function, patient deficiency.   

 

Strength-weight (improved lean body mass to fat ratio) and obesity:  Study shows that 65 years of age men lost 3 kg of fat while gaining 1.9 kg of muscle mass over a 36 month period.    After 3 months of TTT treatment, lean body mass was significantly increased,…  Muscle adaptation to exercise is strongly influenced by anabolic endocrine hormones … whereas TTT and locally expressed IGF-I have been reported to activate muscle stem cells.  Several studies have reported …  maximal voluntary strength in healthy older men.”  It is known that plasma total testosterone (T) is decreased in obese men in proportion to the degree of obesity,”  

 

Osteoporosis & bone density:  The most significant increase in BMD [bone mass density] was seen during the first year of TTT treatment in previously untreated patients, when BMD increased from 95.2 5.9 to 120.0 6.1 mg/cm3 hydroxyapatite (mean SE). Long term TTT treatment maintained BMD in the age-dependent reference range in all 72 hypogonadal men….”  Protects against rheumatoid arthritis.   Low TTT associated with RH.  TTT encourages bone marrow stimulation and reversing the effects of anemia.

 

CVD, Metabolic Syndrome (MetS) , atherogenesis, MI, high cholesterol, obesity, thrombosis: Numerous studies link obesity to low TTT, and genesis of morbid obesity, at, and hypertension.  TTT treatment results in weight loss, at.  Emerging evidence suggests that testosterone therapy may be able to reverse some aspects of metabolic syndrome” metastudy.   And another:  “These results suggest that low SHBG [sex hormone-binding globulin] and/or AD [androgen deficiency, TTT] may provide early warning signs for cardiovascular risk and an opportunity for early intervention in non-obese men.”   In a matched study followed ten years published by the AHA  found that the lowest quarter of men were 41% more likely to die from cancer and cardiovascular disease compared to the highest quarter.  Low TTT is associated with cardiovascular disease. TTT Inhibits atherogenesis:  in a survey paper,  “Positive correlation between total or free testosterone level and HDL and a negative association the LDL” and.   Conclusion:  “A normal physiological level of TTT in men protects against the development of high cholesterol, insulin resistance,  hypertensions, clots that cause heart attacks, obesity, and increased waist:hip ratio, all of which predispose to the development of CVD.  Low or low normal TTT is implicated in the pathogenesis of acute MI and acute stroke.  The decline of TTT with age may explain the greater risk of CVD with advancing years” and [medical terminology simplified by jk].  A literature-review study confirms TTT positive effects upon vascular functions--2012.  After controlling for factors low TTT associated with MI, positive effect upon fibrinolytic pathway, reduces angina.  Current claims counter this are based on recent marketing studies, and a July 2014 Lancet article contradicts those findings.  TTT is good for your heart (2013 review) & health, but not for pharma.

 

Diabetes:  Multiple studies found that type-2 diabetes associated with low TTT, and lowest TTT doubles death rate at, insulin role.  After one year, TTT to exercise and diet 81% improved, vs 31% for those without TTT, also, &.

Prostate Cancer:  Low levels of TTT are associated with both higher risk and disease progression.In our study patients with prostate cancer and low free TTT had more extensive disease”, also, also.  “This finding suggests that low serum free TTT may be a marker for more aggressive disease.”  This evidence calls to question chemical castration for prostate cancer.  The theory that TTT regulates in later life the growth of the prostate organ is without valid support.  Like the penis, the window for growth closes after puberty.  Both organs is a result of DHT not TTT.   Moreover TTT is only essential for prostatic secretion; not its growth.  Harvard Medical School and Prof. Abraham Morgentaler MD, Testosterone for Life, p. 115-139 reviews the source (Dr. Huggins).  They found the work junk science, and not supported by subsequent journal articles.  Very low TTT from castration slows the rate of growth and giving a supplement subsequently stimulates growth.  Only those who had very low testosterone, such as those who aa part of the treatment for prostate cancer experience this effect.  However, for those with normal TTT supplement doesn’t accelerate growth.  Huggins and latter Fowler and Whitmore demonstrated what Prof. Mogentaler calls “testosterone flare” P. 129-131.  A study measure TTT in the prostates showed that with normal level the prostate dose not adsorb more. It is like thirst, once enough more TTT isn’t adsorb.  That is why though TTT supplement for those with normal level don’t experience an accelerated rate of prostate cancer growth.  In fact those with high serum TTT are at significantly lower risk.  The use of TTT in all men as it declines with age below 450 ng/dL, would lower cancer risk,

arcopenia refers to the loss of skeletal muscle mass with age and is associated with low levels of TTT. “We have found a prevalence of sarcopenia of 22.6% in older postmenopausal women not receiving estrogen.”   TTT prevents and reverses sarcopenia in men and women through the simulation of the growth differentiation factor myostatin. 

 

Mood elevation and quality of life & sexual performance:  with all these positive effects both quality of life and mood elevation improve.  DHT & its metabolites have powerful euphoriant, libido, anti-anxiety, & antidepressant effects.   As stated before benefits are dose related, and they come on slowly over a period of one year.   It is NOT a coincidence that as the TTT level drops with age that numerous age-related conditions develop and the quality of life decreases.   Sexual performance and drive improves mainly because of increased strength, endurance, & mental alertness, i.e., general well being.  Quality study at 18 years found the lowest 1/3rd had a 33% greater death rate.   At youthful level TTT dramatically improves  health, quality, and duration of life.   

 

Testosterone and longevity, while the literature fails to address this question in population studies, and is nearly void on the effects of restoring in the elderly their TTT level to that of range for a 20-year old; but given the above benefits, including increased energy (drive) for physical exertion it is reasonable to conclude guestimate at least a 4 year extension in life.  A look at elderly weight lifters (obviously on androgens confirms this conclusion. 

 

TTT for women:  Cognitive function:  “Effects of testosterone on visual-spatial performance has been suggested by enhanced performance in females exposed prenatally to excess androgens.  Women with higher scores on mental status had significantly higher total and bio-available testosterone levels.” (Moffat).  In a study of women 55-88 years of age, those with the higher levels of TTT adjusted for age performed significantly better. Sexual desire:Compared with placebo, women receiving the 300-g/dL testosterone patch had significantly greater increases from baseline in sexual desire (67% vs 48%P = .05) and in frequency of satisfying sexual activity (79% vs 43%P = .049).” Vaginal estrogen creams and TTT reverse vaginal atrophy.  Mood elevation:  The positive-well-being, depressed-mood, and composite scores of the Psychological General Well-Being Index also improved at the higher dose”.   Concern over masculinization is misplaced: the dose is insufficient and dihydrotestosterone (not TTT) is responsible for masculinization.  Women body builders use a very high dose of androgens.  Third reason in the 80’s and 90’s there was widely marketed, mainly in Europe, a formulation of HRT with TTT (instead of progestin), still sold in the US as Estratest.   TTT patch for women is available.  See the 3 pages on HRT for list of benefits, especially for natural HRT of estradiol and progesterone.

 

RECOMMENDATIONS:  Since 2003 JK have used TTT 1/2 tsp 10% (60 grams/month) lotion from a compounding pharmacy--increased to 15% when I reached 68 years—necessitated by the lower bioactivity as TTT receptors age and SHBG drops.  JK is taking 4 times the highest dose available in patented formulas[1], and made even higher by improved absorption.  Only about 10% of topical TTT passes through the skin, thus 100 mg is equal to a 10mg injection.  Apply widely as possible over the torso, back, shoulders, underarms, and face using water and rubbing it in to promote better absorption. For JK with the higher dose of 150 mg, leg cramping vanished, joint are excellent, and skin has become much tougher on forearms.  JK notices from 12 years of use: cognitive benefits, increased energy, feeling well, resistance to weight gain, improved muscle tone, tight abs, moderate increase in strength as to weight load at the gym; looking younger has sexual/romantic benefits.  JK’s TTT level averages the youthful 850 ng/dL, and his muscle tone reflects this.  Pharma for financial reasons offers bio-ineffective doses.  Some doctors make a career out of hormone balancing.  Recommended:  10% 1/2th tsp when TTT level is below 450 ng/dL, increased to 15% at age 70--lotion from compounding pharmacy.   A daily 325 mg of aspirin lowers the risk of prostate cancer and other cancers at least 30% through the stimulation of the body’s necrosis factor for destruction of abnormal cells, at, and, and. In the feedback system, adding TTT lowers testicular production of TTT and also sperm count.  See Morgentaler supra, 145-7 for discussion of this issues including possible reduction in testicular size.  Only oral form of TTT taken long-term poses risk of liver damage.  The TTT patch can cause a skin rash. “Multiple studies of prostatic hyperplasia (BPH) have failed to show that the size of the prostate enlarges substantially with TTT therapy or causes a diminution in urinary function,” Morgentaler supra 149.  For above reasons high dose lotion of TTT is highly recommended. 


[1] Androgel 1.62% in 5 gm = 81 mg.  JK 2.5 gm at 15% = .375 gm daily is over 4 times that of Androgel.  My testosterone level is 1011 ng/dL.  With the higher dose results gradually improved as to appetite, mood excellent, weight constant without dieting, joint pain vanished, strength increased about 15% over 5 years, physical endurance and libido has steadily declined.  I am in the 7th decade.   


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Testosterone:   the male hormone that is almost identical in structure to estrogen and thus has many of the same benefits as estrogen.  Noticeable benefits for testosterone:  quality of life in 4 weeks, depressed mood in 30 weeks, bone mass in 26 weeks,  lipid profile in 52, inflammation in 12 weeks, sexual interest in 6 weeks, erection/ejaculation in 26 weeks,  red cells in  52 weeks, insulin sensitivity in 52 weeks , muscle strength in 16 weeks, fat mass in 16 weeks (Eur J Endocrinol. 2011).  Other benefits include improved cognitive function, reduced risk for Alzheimer’s disease, metabolic syndrome, diabetes, cardiovascular disease and the resultant heart attacks and strokes.  The negative claims made for testosterone is from pharma’s marketing science.  It is not associated with higher cholesterol levels or prostate cancer, but rather the reverse.  Testosterone does not cause or produce deleterious effects on prostate cancer Wiki.  Recommended: once serum cholesterol level drops below 450, to use 100 mg of testosterone in a topical cream (10% tsp.) from compounding pharmacy.  Commercial preparations are too weak.   Ideal level is 850 to 1000 ng/dL, or higher.  Increased to 15% mg at age 70 as effects diminish--bio-receptors and response decreases with age as does the level of free (available) testosterone.  Current assay methods are inaccurate as to measure of free testosterone.   Apply widely as possible over the torso, back, shoulders, underarms, and face using water and rubbing it in to promote better absorption.  Doctors who follow a program of hormone balance are milking the insurance and patient. 






GH, Growth hormone:  Sometimes used with TTT.  On the other hand, most studies have shown that administration of GH alone failed to improve muscle strength despite amelioration of the detrimental somatic changes of aging. Both GH and TTT are anabolic agents that promote muscle protein synthesis and hypertrophy but work through separate mechanisms, and the combined administration of GH and TTT, albeit in only a few studies, has resulted in greater efficacy than either hormone alone.  This is consistent with both medical literature and belief held by body builders on “the juice” (androgens & GH).  Further studies are needed to access the long-term consequences of the combo of GH and TTT. GH must be injected. Alternates, including enhancers are probably a scam.  If reputable lab studies aren’t done and published, expect the worse. 


 


 


 


Possible the castrating of men with terminal prostate cancer started with the use of estrogen in high doses which has similar effect.  See http://www.sciencedirect.com/science/article/pii/S0022534705636579


 



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Extended footnote for web pages.  Precocious puberty from Wikipedia:


TTT is made both by girls and boys, pre-puberty.  The FDA used 8 cases of reported aggression or genitalia enlargement as the reason for the black-box warning.  There was no laboratory investigation to prove that those events were caused by father who applied topical TTT.  No proof was sought by the FDA, just anecdotal reports.  Precocious sexual develop occurs in a small number of children.  In my class in 3rd grade, for example, one girl was developing breasts. Moreover, the patch, the most commonly sold form of TTT, is covered and adheres to the skin, thus contact by the child would not occur.  Finally, if the source is a lotion from a compounding pharmacy (under 10% of total sales), then transfer through contact is possible.  But very few fathers take TTT, making such transfer unlikely.  Other relatives would have too infrequent contact.  And such contact must be on the area applied, usually the underarm or chest.  But prolonged contact with these parts of the body are high unlikely for a prepubescent boy. Moreover, casual contact would not contribute appreciable to the level of TTT in the child.  If the FDA wanted to prove that transfer was possible, they could easily construct a test with tagged TTT, and have 2nd person rub against the person where the tagged TTT has been applied using a topical lotion from a compounding pharmacy.  Then they would a day later take a blood sample and see what percentage of TTT of total TTT is tagged.  Without testing the reports are not based on science.  The FDA simply relied upon 8 filings of reports the phenomena of either aggression or genital enlargement in a prepubescent boy.  The FDA made no effort to separate cases to investigate the causes of precocious puberty, which has numerous natural causes.  A search of www.scholar.google.com list many of such causes, and at the bottom of page two a case study that could have been from exposure to testosterone, though no causal nexus was firmly established, and the authors were uncertain as to cause (published in an obscure journal).  Possible PhARMA was instrumental in generating those reports filed with the FDA through PhARMA friendly physicians.  The FDA doesn’t issue black-bow warnings for block-buster drug on anecdotal evidence.  Another hatchet job done by PhARMA’s and the FDA on TTT—business as usual. 


 


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Early menarche and male sexual maturity:   A point of interest, and puzzle, has been not just the steady increase in height over the last 2 centuries, but also the march toward younger age of menarche in women and male sexual maturity, In England, the average in 1840 was 16.5 years…. A 2006 study in Denmark found that puberty, as evidenced by breast development, started at an average age of 9 years and 10 months, a year earlier than when a similar study was done in 1991…. Early stages of male hypothalamic maturation seem to be very similar to the early stages of female puberty, though occurring about 1–2 years later.”  see http://en.wikipedia.org/wiki/Puberty#Historical_shift.    


 


Prostate cancer and TTT:  Contrary to accepted wisdom.  It has been long assumed that testosterone stimulates the growth of prostate cancer; just like estrogen does for breast cancer.  It is standard procedure to proscribe a drug that blocks testosterone (pharmaceutical castration), the equivalent is done to women with breast cancer.  This assumption is false. Numerous studies have instead of finding a negative effect for TTT (& estradiol for women) find a positive TTT relation of lower risk and less aggressive.  The reason lies in the nature of cancer and the approval process.  Typical of PhARMA tests a chemotherapy on stage iv patients (terminal), find that extends their life on an average around 2-3 months for FDA approval, then markets it for all stages.  However the majority of stage i-iii cancers are of the indolent type, and haven’t developed the ability to metastasize, thus often the finding for terminal cancer cannot be validly extended.  Moreover if it is aggressive and discovered in an early stage, the outcome will is still the same.  Survival for ng has minimal affect on prognosis.  Thus blocking sex hormones has little benefit if metastatic, and if not hormone blocking increases long-term mortality rate and lowers quality of life.  So too does operating on localized prostate cancer have little effect on the course;  16 patients with localized prostate cancer would need to receive radical prostatectomy rather than watchful waiting in order to prevent one death due to prostate cancer…. However, in men older than 65, there was no statistically significant risk reduction even when adjusted for PSA level, Gleason score and tumor stage.” (http://en.wikipedia.org/wiki/Prostate_cancer).  Like with lung cancer and other types, if it is aggressive, finding it early makes little difference.  Removing a cancer offers a modest advantage, mainly because over years an indolent can mutate to become aggressive—risk goes up with time and number of indolent cancer cells.   


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Falling TTT Levels since 1900:  The normal level of testosterone for an 80 year old has steadily fallen since 1984 from 450 to under 250 in 2004.  Three principle causes are statins, polypharmacy (taking multiple drugs), & obesity.  Moreover, estrogen is known to reduce the production of testosterone.  There is an assortment of evidence which show that estrogen mimics occupy estrogen receptors and thereby cause both the reduction of the production of testosterone and increase appetite (as though pregnant).  Disconcerting is NIH shift in standard for low TTT and its affect upon medical practice.   The normal level for an 80 year old in 1984 (450 ng/dL), as high a person aged 50 today, see Boston study.  The current NIH’s standard for low TTT is under200 ng/dL.  In the meantime, truly hypogonadal men (those who are symptomatic men and have a serum testosterone concentration below 200 ng/dL) who have no contraindications to testosterone replacement therapy (e.g., prostate cancer) may benefit from testosterone replacement regardless of whether they are 30 or 80 years of age.”  Over and over again the record show that NIH acts in the interest of big PhARMA and contrary to the public’s health.  The negative position of NIH on testosterone is one more example.

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GH, Growth hormone:  Sometimes used with TTT.  On the other hand, most studies have shown that administration of GH alone failed to improve muscle strength despite amelioration of the detrimental somatic changes of aging. Both GH and TTT are anabolic agents that promote muscle protein synthesis and hypertrophy but work through separate mechanisms, and the combined administration of GH and TTT, albeit in only a few studies, has resulted in greater efficacy than either hormone alone.  This is consistent with both medical literature and belief held by body builders on “the juice” (androgens & GH).  Further studies are needed to access the long-term consequences of the combo of GH and TTT. GH must be injected. Alternates, including enhancers are probably a scam.  If reputable lab studies aren’t done and published, expect the worse. 

 

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Extended footnote for web pages.  Precocious puberty from Wikipedia:

TTT is made both by girls and boys, pre-puberty.  The FDA used 8 cases of reported aggression or genitalia enlargement as the reason for the black-box warning.  There was no laboratory investigation to prove that those events were caused by father who applied topical TTT.  No proof was sought by the FDA, just anecdotal reports.  Precocious sexual develop occurs in a small number of children.  In my class in 3rd grade, for example, one girl was developing breasts. Moreover, the patch, the most commonly sold form of TTT, is covered and adheres to the skin, thus contact by the child would not occur.  Finally, if the source is a lotion from a compounding pharmacy (under 10% of total sales), then transfer through contact is possible.  But very few fathers take TTT, making such transfer unlikely.  Other relatives would have too infrequent contact.  And such contact must be on the area applied, usually the underarm or chest.  But prolonged contact with these parts of the body are high unlikely for a prepubescent boy. Moreover, casual contact would not contribute appreciable to the level of TTT in the child.  If the FDA wanted to prove that transfer was possible, they could easily construct a test with tagged TTT, and have 2nd person rub against the person where the tagged TTT has been applied using a topical lotion from a compounding pharmacy.  Then they would a day later take a blood sample and see what percentage of TTT of total TTT is tagged.  Without testing the reports are not based on science.  The FDA simply relied upon 8 filings of reports the phenomena of either aggression or genital enlargement in a prepubescent boy.  The FDA made no effort to separate cases to investigate the causes of precocious puberty, which has numerous natural causes.  A search of www.scholar.google.com list many of such causes, and at the bottom of page two a case study that could have been from exposure to testosterone, though no causal nexus was firmly established, and the authors were uncertain as to cause (published in an obscure journal).  Possible PhARMA was instrumental in generating those reports filed with the FDA through PhARMA friendly physicians.  The FDA doesn’t issue black-bow warnings for block-buster drug on anecdotal evidence.  Another hatchet job done by PhARMA’s and the FDA on TTT—business as usual. 

 

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Early menarche and male sexual maturity:   A point of interest, and puzzle, has been not just the steady increase in height over the last 2 centuries, but also the march toward younger age of menarche in women and male sexual maturity, In England, the average in 1840 was 16.5 years…. A 2006 study in Denmark found that puberty, as evidenced by breast development, started at an average age of 9 years and 10 months, a year earlier than when a similar study was done in 1991…. Early stages of male hypothalamic maturation seem to be very similar to the early stages of female puberty, though occurring about 1–2 years later.”  see http://en.wikipedia.org/wiki/Puberty#Historical_shift.    

 

Prostate cancer and TTT:  Contrary to accepted wisdom.  It has been long assumed that testosterone stimulates the growth of prostate cancer; just like estrogen does for breast cancer.  It is standard procedure to proscribe a drug that blocks testosterone (pharmaceutical castration), the equivalent is done to women with breast cancer.  This assumption is false. Numerous studies have instead of finding a negative effect for TTT (& estradiol for women) find a positive relation of lower risk and less aggressive.  The reason lies in the nature of cancer and the approval process.  Typical of PhARMA tests a chemotherapy on stage iv patients (terminal), find that extends their life on an average around 2-3 months for FDA approval, then markets it for all stages.  However the majority of stage i-iii cancers are of the indolent type, and haven’t developed the ability to metastasize, thus often the finding for terminal cancer cannot be validly extended.  Moreover if it is aggressive and discovered in an early stage, the outcome will is still the same.  Survival for ng has minimal affect on prognosis.  Thus blocking sex hormones has little benefit if metastatic, and if not hormone blocking increases long-term mortality rate and lowers quality of life.  So too does operating on localized prostate cancer have little effect on the course;  16 patients with localized prostate cancer would need to receive radical prostatectomy rather than watchful waiting in order to prevent one death due to prostate cancer…. However, in men older than 65, there was no statistically significant risk reduction even when adjusted for PSA level, Gleason score and tumor stage.” (http://en.wikipedia.org/wiki/Prostate_cancer).  Like with lung cancer and other types, if it is aggressive, finding it early makes little difference.  Removing a cancer offers a modest advantage, mainly because over years an indolent can mutate to become aggressive—risk goes up with time and number of indolent cancer cells.   

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Falling TTT Levels since 1900:  The normal level of testosterone for an 80 year old has steadily fallen since 1984 from 450 to under 250 in 2004.  Three principle causes are statins, polypharmacy (taking multiple drugs), & obesity.  Moreover, estrogen is no to reduced the product of testosterone.  There is an assortment of evidence which show that estrogen mimics occupy estrogen receptors and thereby cause both the reduction of the production of testosterone and increase appetite (as though pregnant).  Disconcerting is NIH shift in standard for low TTT and its affect upon medical practice.   The normal level for an 80 year old in 1984 (450 ng/dL), as high a person aged 50 today, see Boston study.  The current NIH’s standard for low TTT is under200 ng/dL.  In the meantime, truly hypogonadal men (those who are symptomatic men and have a serum testosterone concentration below 200 ng/dL) who have no contraindications to testosterone replacement therapy (e.g., prostate cancer) may benefit from testosterone replacement regardless of whether they are 30 or 80 years of age.”  Over and over again the record show that NIH acts in the interest of big PhARMA and contrary to the public’s health.  The negative position of NIH on testosterone is one more example.

 

 

 

Lowering the level for normal for elderly:  a way to get the doctors to not write scripts

More tricks beside black bock warning and association with prostate cancer:  NIH states that between 300 and 200 is borderline hypogonadal, while under 200 should be treated.  However, the average level for an 80 year old is 370 ng/dL.   http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2686341/  which is a very good article but for several such pro-pharma spins.  At http://jcem.endojournals.org/content/92/1/196.full  Average level of a 45 & 50 year old is 537, 60 years 517, and both 70 & 80 years 517 measured in 1987-89.  Inexplicable the levels dropped for the same group at intervals 1995-97 and 2002-04.  The 50-year olds in 95-97 had level of485, the 60s at 476, and the 70-80 at 471.  However the 2002-04 showed a major decline.  The 60s at 436, the 70s at 436, the 80s at 368.  Among causal factors is the increase in obesity and polypharmacy over the course of follow-up. Counter is trend is a major reduction in cigarette smoking.  The article noticed this:  Results were essentially unchanged when all covariate effects (see Subjects and Methods) were included in multivariate.  The chart for 1919 shows the level to be 545 for an 80 year person.  Plastic wear for foods became popular in the 1970s. A number of sources find a connection to bisphenols and like compound whose main source of exposure comes from food and water containers.  “Bisphenol A is an endocrine disruptor which can mimic estrogen and has been shown to cause negative health effects in animal studies. More specifically, bisphenol A closely mimics the structure and function of the hormone estradiol with the ability to bind to and activate the same estrogen receptor as the natural hormone… A 2011 rodent study found that male rats exposed to BPA had lower sperm counts and testosterone levels than those of unexposed males.”  Wiki



At http://jcem.endojournals.org/content/92/1/196.full  http://jcem.endojournals.org/content/92/1/196.abstract


Massachusetts Male Aging Study (wave T1, T2, & T3) it show those in 1987 to 1989, were over 2)% higher than the group tested in 1995-97; and T3 in 2002-2004 another drop of 20% mostly among those in the 75-80 age group.  Thus in a 20 year period the “normal (average) level of TTT dropped 40% among the elderly.   


 



 

 

 



Junk science:  http://www.nejm.org/doi/full/10.1056/NEJMoa054629#t=articleTop   What is normal now for a 65-year old was male in 1990 is lower in 2003 (515 compared to just 430 ng/dL).  Since1920, when reliable figures became available, there has been a stead drop in TTT level.  A 80-year old’s level averaged 470 in 1919, and in 2003 380 ng/dL, at.  Two sources of estrogen mimics as possible causes are soy products and the bisphenols like softeners added to PVCs. 


One example of such is a study in 2006 where eligible men were over the age of 60 and had a “bioavailable levels that was less than 103 ng/dL (average 50 ng/dL). This is about 1/4th the level of an 80-year olds listed in JCEM article. And the dose was just 5 mg transdermal; too low to produce significant results.  Average level at 2 years of treatment was 75 ng/dL; still well below the 380 level (see tables). The NEJM article found no changes at 2 years.  One letter published on article criticized the results because “replacement administered failed to achieve physiologic testosterone levels” and another for the lack of physical exercise which is needed to be part of treatment to improve physical function compared to placebo group. The two lead authors of this article are thought leaders who receive lecture grants from 5 major pharmaceutical companies—another hatchet job.    


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WARNINGS:  METHYLTESTOSTERONE, testosterone cypionate, and testosterone undecanoate used long term are associated with liver toxicity, all of which are orally active.  Estrogen associated with lower level of TTT through inhibition effect. Soy bean has estrogen mimic, which is possible the cause for the falling TTT levels over the last 100 years.   


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Androgel the leading product comes in 1 and 1.672% dose.  20.25 mg TTT/pump.  Each pump dispenses 1.25 gm gel.  Comes in 75 gm container.  2 pumps would result in 2.5 gms = 30 day supply which runs ~$425/month for 40.5 mg of TTT daily.  JK was getting 200 mg/day (10% of 2gm in 60 gm container) 200 mg of TTT, now raised to 300 mg of TTT. 


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[1] One example of such is a study in 2006 where eligible men were over the age of 60 and had a “bioavailable levels that was less than 103 ng/dL (average 50 ng/dL). This is about 1/7th the level of an 80-year olds in 2004 listed in JCEM article. And the dose was just 5 mg transdermal; too low to produce significant results.  Average level after 2 years of treatment was 75 ng/dL; still well below the 380 level (see tables). The NEJM article found no changes at 2 years.  One letter published criticized the results because “replacement administered failed to achieve physiologic testosterone levels” and another for the lack of physical exercise which is needed to be part of treatment to improve physical function compared to placebo group. The two lead authors of this article are thought leaders who receive “grants” for lectures from 5 major pharmaceutical companies—another successful hatchet job by pharma, as of 5/1/2014 this article had 134 citations.  Two low a dose, a typical population, and bias in the article are three tools of tobacco science Since pharma funds and thus is involved in 90% of the clinical trials, this sort of manipulation is the norm.  In the present case there were grants from the FDA, Department of Medicine Mayo Clinic, and the Mayo foundation.  However, the selection of leads for the trial and its marketing science (pharma opposes TTT) is dispositive as to the role the behind-the-stage role of pharma,     


 

 

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2686341/  which is a very good article but for several such pro-PhARMA spins.  At http://jcem.endojournals.org/content/92/1/196.full  Average level of a 45 & 50 year old is 537, 60 years 517, and both 70 & 80 years 517 measured in 1987-89.  Inexplicable the levels dropped for the same group at intervals 1995-97 and 2002-04.  The 50-year olds in 95-97 had level of485, the 60s at 476, and the 70-80 at 471.  However the 2002-04 showed a major decline.  The 60s at 436, the 70s at 436, the 80s at 368.  Among causal factors is the increase in obesity and polypharmacy over the course of follow-up. Counter is trend is a major reduction in cigarette smoking.  The article noticed this:  Results were essentially unchanged when all covariate effects (see Subjects and Methods) were included in multivariate

At http://jcem.endojournals.org/content/92/1/196.full  http://jcem.endojournals.org/content/92/1/196.abstract

 

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Disclaimer:  The information, facts, and opinions provided here is not a substitute for professional advice.  It only indicates what JK believes, does, or would do.  Always consult your primary care physician for medical advice, diagnosis, and treatment.