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. Keeping the youthful- level of TTT has major health benefits for both men past 60 and women past 50. [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 1/7^th 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.

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.

Vascular aging slowed: TTT is good for endothelial cells, the gate keepers in the artery walls thus preventing CVD Campelo et al., 2012, and Foresta et al., 2008 .  Lowers blood pressure a causal factor for CVD through nitrous oxide production Yue et al., 1995 and  Nguyen et al., 2011 reduces arterial stiffness Yaron et al., 2009.  Promotes production of prostaglandins, thus interfere with vascular function via changes in the thromboxane/COX pathway Cheuk et al., 2000; Song et al., 2004.   For in depth summary article click on link.

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,

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.  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 1/3^rd 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-µg/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[3], 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% 1/2^th 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.