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.  In another important study, Hammond et al.¹⁸ found that testosterone was protective of human primary neurons in culture, providing the most direct evidence for neuro-protective effects of testosterone on human neural tissue”(Moffat). These finding are widely supported.  Equivocal finding are because of design:  short duration and low dose. 

Alzheimer’s (AD) &cognitive functions:  Beta amyloid accumulation in the brain is the physical manifestation for Alzheimer’s disease (AD). “Testosterone decreases amyloid secretion from rat cortical neurons¹⁵ and reduces amyloid-induced neurotoxicity in cultured hippocampal neurons.¹⁶ (Moffat).  Testosterone reduces neuronal secretion of Alzheimer's β-amyloid [Aβ] peptides.  Based on in vitro study a decrease in Aβ release also was observed.  “Importantly, in this prospective longitudinal study, we quantified long-term testosterone concentrations in individuals prior to the diagnosis of dementia.³⁸ This was done by restricting assays only to those blood samples that were provided 2, 5 and 10 years prior to the diagnosis of AD diagnosis (FIG. 3). Consistent with the results of other studies, we observed lower free testosterone levels in individuals diagnosed with AD compared to controls (FIG 4). More specifically, the results of this study revealed an approximately 10% reduction in the risk for AD for each unit increase in free testosterone. These results were robust with respect to restricting testosterone values to 2, 5 and 10 years prior to AD diagnosis. (Moffat; a 26% decrease for each 10-nmol/nmol FTI increase.  Also TTT reduces the rate of age-related cognitive decline.

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….”  It has no effect on those with normal TTT levels the article explains.    TTT encourages bone marrow stimulation and reversing the effects of anemia.

Metabolic syndrome MetS (poor cholesterol profile, obesity, and high blood pressure):  “Emerging evidence suggests that testosterone therapy may be able to reverse some aspects of metabolic syndrome”  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” [medical terminology simplified by jk].  TTT is good for your heart, muscles, and blood vessels. 

Heart Attack, after controlling for factors low TTT associated with MI, positive effect upon fibrinolytic pathway, reduces angina.

Diabetes:  Multiple studies found that diabetes is clearly associated with low TTT, and monitor of TTT is recommended for middle aged men.   After one year, adding TTT to exercise and diet reversed MetS in 81%, compared to 31% for those without TTT, also.

Prostate cancer:  Low levels of TTT are associated with prostate cancer, aggressive prostate cancer, and disease progression. “In our study patients with prostate cancer and low free TTT had more extensive disease.  In addition, all men with a biopsy Gleason score of 8 or greater had low serum free testosterone. This finding suggests that low serum free testosterone may be a marker for more aggressive disease.”  The practice of chemically castrating men with prostate cancer cannot be justified given these findings.  Similar finding for breast cancer and low estrogen.  Wikipedia support these conclusions.  PhARMA has no conscience.

Sarcopenia 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.  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-relate d 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.  The issue is not “what is normal TTT at your age,” but what level of TTT dramatically improves your health and quality of life. 

TTT for women:  Cognitive function:  “Effects of testosterone on visuo-spatial performance has been suggested by enhanced performance in females exposed prenatally to excess androgens^19,20” (TTT 13 pgs) “Women with higher scores on mental status had significantly higher total and bioavailable 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-µg/d 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).” Mood elevation: “The positive-well-being, depressed-mood, and composite scores of the Psychological General Well-Being Index also improved at the higher dose [of testosterone]”.   The concern over masculinization is misplaced (contrary to the teachings of PhARMA) because the dose is insufficient and it is not TTT but dihydrotestosterone (DHT) that is responsible for masculinization.  Other evidence:   go to a gym and take a look at women body builders.  To obtain such muscle mass requires the use of androgens several times that of a young men; nevertheless, they aren’t hairy or their voices deep.  Second, in the 80’s and 90’s there was marketed a formulation of HRT using TTT, a form of which is still sold as Estratest.   TTT patch for women is available.  See the 3 pages on HRT last page for details.

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 wose. 

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 2^nd 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. 

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.    

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 assumptions 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.   

The normal level of testosterone for an 80 year old has steadily fallen since 1984 from 450 to under 250.  The two principle causes are statins, polypharmacy (taking multiple drugs), and obesity; however, that doesn’t explain the entire drop.  JK suspects that estrogen mimics, food additives, and herbicides could account for the remainder of the drop.  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.  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.”  

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. 

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