Testosterone Improves Muscle Mass ... - Hormone Restoration



Rough Draft: Testosterone Optimization for Men9810752315210Male testosterone levels are 10 times greater than those of women. Testosterone is responsible of most male characteristics, including much greater muscle size and strength, reduced fearfulness, and greater libido. Testosterone increases the growth of body hair and of facial hair in particular. Men’s testosterone levels gradually decline after age 25. The free testosterone level declines by about 2% per year. Between the ages of 20 and 80, free testosterone declines by 50%. This decline is due to the age-related deterioration of both the hypothalamic-pituitary system (less LH production) and the testes (reduced numbers of Leydig cells)., Stress, obesity, and alcohol intake also reduce testosterone levels. Men with good health and habits have testosterone levels 10-15% higher, but suffer the same rate of decline. Baltimore Longitudinal Study of Aging (BLSA). Harman et al., 2001 Hypothyroidism lowers free testosterone levels due to lower gonadotropin secretion. Thyroid replacement therapy can restore testosterone levels. Obesity produces lower testosterone in men, which further promotes fat accumulation. Fatty tissue contains high levels of aromatase that converts testosterone to estradiol. Higher estradiol levels as the primary feedback signal to the HP axis to lower LH secretion, leading to lower testosterone secretion. This has been called the hypogonadal-obesity cycle. DHT levels tend to rise with age, producing a higher DHT:T ratio than in young men. This ratio reverts to normal with testosterone supplementation.With the loss of testosterone with age, men notice decreased muscle size and strength. They cannot build muscle with weight training as they could when they were younger. They are not a sharp mentally. They are more hesitant to make decisions involving risk. Lower testosterone levels within the reference range are associated with anxiety. Their libido is lower and they no longer have spontaneous erections during the night. Very low testosterone levels, below the reference range, are associated with depression and diabetes. Because male andropause is gradual and incomplete, it is much less obvious than female menopause. Men believe that they "just getting old". They don’t understand that much of what they are experiencing is due to lower hormone levels. As with other hormones, conventional medical opinion about testosterone is lagging far behind the scientific evidence. In the near future it will become standard medical practice to restore youthful levels of this essential and beneficial hormone to both men and women.Table 2. The Benefits of Testosterone Restoration in MenImproved energy, mood and motivationImproved libido and erectile functionReduction in anxietyGreater physical stamina, enduranceGreater muscle mass and strengthReduced fat around waist, hipsReduced visceral (belly) fat Better memory and mental clarity Greater bone mass, less fracture riskGreater insulin sensitivityLower blood pressure The evidence of the benefits of testosterone optimization is abundant. Many studies show that higher levels of testosterone within the reference range protect against cardiovascular disease, diabetes, dementia, hypertension, abdominal obesity and arthritis. In hypogonadal men, testosterone enanthate injections of 100mg per week improve muscle mass, reduce subcutaneous fat and overall fat mass, and improve bone density., Testosterone replacement therapy (TRT) reduces intra-abdominal fat, thereby reducing the waist-hip ratio. Testosterone optimization increases muscle strength, bone mass, erectile function, and mood. With injected testosterone undecanoate mental and psychosexual functions (libido, vigor, overall mood, and ability to concentrate) improved markedly, while mean waist circumference decreased. Blood pressure and lipid parameters improve. Nearly every study of testosterone and heart attacks shows that men with lower levels of testosterone have higher risk. A striking experiment in this regard is androgen deprivation therapy. Men with widespread prostate cancer are treated by lowering their testosterone levels to those of a woman. These men have been found to develop heart disease, diabetes, and metabolic syndrome. Testosterone Improves Muscle Mass and StrengthThe improvements that higher testosterone levels on replacement bring in muscle mass and strength and reduced fat mass are well-known. In another study of superphysiological dosing (10 times replacement dose), men who did not exercise gained 3kg of muscle, whereas those who exercised gained 6kg. Strength increased proportionately and no increase in anger or aggression was reported.In undernourished elderly men and women, testosterone replacement plus a nutritional supplement greatly reduced the rate of hospital admissions and time in hospital. Older men with testosterone levels in the lower quartile of the reference range have reduced physical performance and a 40% higher risk of a fall. Testosterone injections give to elderly men increase muscle protein synthesis and strength. In elderly men, higher free testosterone levels within the range are associated with lower fat mass, higher muscle strength and higher bone mass.Testosterone Improves Mood and Energy and Sense of Well-BeingLower testosterone levels within the reference range are associated with depressive symptoms. TRT is an effective treatment for depression in men with testosterone levels less than 350nd/dL., Contrary to popular misconceptions, testosterone optimization does not cause anger or aggression. It makes men more patient, more sociable, and less prone to anger. They feel more energetic and vital. Testosterone replacement has marked psychological benefits. It reduces nervousness, fatigue, and irritability and increases friendliness and sense of well being. Even in high suprephysiological doses, testosterone administration does not increase anger or aggression. Superphysiological doses of testosterone enanthate (200mg weekly) produced peak level 400 to 500% above baseline increased sexual awareness and arousability but did not increase aggressive feelings.Testosterone Replacement Does not Promote Heart DiseaseA 2010 review of 51 studies of testosterone replacement lasting from 3 mos to 3 yrs found no increase in mortality, prostrate, or cardiovascular outcomes. Studies of testosterone undecanoate injections for 2 yrs and scrotal testosterone patches for 7 to 10 yrs did not show any increase in mortality or morbidity. A large review revealed that low endogenous testosterone levels are associated with increased risk of all-cause and cardiovascular death in men. Another review found that low testosterone is associated both with CVD and CV morality. A study involving a 10 yr follow-up of 11,000 men should that lower endogenous testosterone levels are associated with a higher risk of death from all causes including cardiovascular disease and cancer. The risk of death was progressively lower with higher testosterone levels by quartile. Of course, higher testosterone levels may just be a marker for better health, but there are many known mechanisms by which higher testosterone levels improve health. Persons who have had a myocardial infarction h higher fibrinogen levels, higher waist-hip ratio, and higher lipoprotein (a) levels; higher testosterone levels in men, endogenously or by replacement, are known to reduce all three of these risk factors. Lower testosterone and estradiol levels are associated with higher risk of mortality in men. Low testosterone was associated with elevated mortality in male veterans. In a 7.2 yr follow-up, low testosterone levels were associated with a 2.5 – fold risk fo death from CV disease and a 3.5-fold risk of death from cancer. During an average 11.8yr follow-up, men with testosterone levels < 240ng/dL were 1.4 times more likely to die from any cause, mostly from CV and respiratory diseases. The evidence linking low testosterone to CV disease and risk factors for CV disease is so strong that is low testosterone should be considered a major cardiovascular risk factor., A meta-analysis of 19 randomized controlled trials lasting at least 90 days revealed no increase in cardiovascular events in testosterone-treated men. Testosterone metabolites, DHT and estradiol, have opposing effects on vascular cell adhesion molecule-1 expression, which promotes atherosclerosis. ,In several studies of men undergoing coronary angiography, those with coronary artery disease had lower total and free testosterone levels than those who were disease-free., Lower total and free testosterone has been associated with coronary artery disease, lower cardiac ejection fraction, and higher diastolic blood pressure. In men with an acute myocardial infection, testosterone levels are lower than men with normal coronary arteries. Older men with lower testosterone levels have higher common carotid artery intimal thickness (a measure of atherosclerosis). Lower free testosterone levels are associated with higher mortality from cardiovascular disease. Lower total and free testosterone levels in elderly men are associated with a higher risk of aortic atherosclerosis. Testosterone supplementation with high dose injections( 200mg of testosterone cypionate weekly) reduced post-exercise ST-segment depression, probably by improving the dilation of coronary blood vessels. Testosterone infusions into the coronary arteries of men with heart disease increase both coronary artery diameter and blood flow. Testosterone replacement therapy with injections in hypogonadal and elderly has a beneficial effect on lipid metabolism. It decreases total cholesterol levels and levels of atherogenic fraction of LDL-cholesterol without significantly affecting HDL-cholesterol levels or its subfractions HDL2-C and HDL3-C. Superphysiological testosterone replacement with injections lowers total cholesterol but mostly by lowering HDL cholesterol. , In contrast, in untreated males, higher testosterone levels correlate with higher HDL levels, and higher estradiol levels correlate with lower LDL levels., Supraphysiological testosterone injections 200mg weekly lower HDL and HDL 2 and 3, LDL was unchanged. Body weight increased by 4kg. No increase in self-reported aggressive behaviors. Over a 6-month period, transdermal TRT was associated with beneficial effects on insulin resistance, total and LDL-cholesterol, Lpa, and sexual health in hypogonadal men with type 2 diabetes and/or metabolic syndrome. Testosterone and Blood-Clotting RiskHigher endogenous testosterone levels are associated with lower measures of blood-clotting risk. Higher testosterone correlates with higher levels of the major stimulator of fibrinoloysis, tissue plasminogen activator activity, and lower levels of two coronary heart disease indicators, plasminogen activator inhibitor activity and fibrinogen levels., In men who had had an MI, the most significant difference with control were their higher fibrinogen and Lp(a) levels, both of which are associated with lower testosterone levels.Higher endogenous testosterone levels are associated with lower blood pressure. Testosterone replacement tends to lower diastolic blood pressure.Increased markers of a hypercoagulable state are strong predictors of fatal coronary disease in men. Blood clotting tendency is increased with obesity, diet, increasing age, insulin resistance, smoking, female sex in childbearing age, pregnancy, oral contraceptives. Several known inherited coagulation disorders antithrombin III, protein C and protein S deficiency, factor V Leiden mutation, and antiphospholipid antibody syndrome that can lead to hypercoagulability increase the risk of venous and arterial blood clotting. It has been reported that hyperestrogenaemia might cause an increase in platelet count, fibrinogen and von Willebrand factor, and a decrease in antithrombin III level. Estradiol levels rise in women throughout pregnancy reaching their highest point at delivery, 20 times higher than normal peak levels during menstrual cycles. This causes the greatest risk of thrombosis around delivery. Estradiol injections in rats producing human pregnancy levels greatly increased the tendency to form blood clots. High estradiol levels caused by ovarian stimulation are associate with thrombosis. Thus, increased endogenous estrogen levels appear to induce the so-called "hypercoagulable state" through both an increase in coagulation factors in the coagulation cascade system and a decrease in antithrombin III, a potent natural inhibitor of activated coagulation factors. Myocardial infarction has even been seen in women undergoing ovarian stimulation in whom very high estrogen levels cause hemoconcentration and hypercoagulability. The TOM study of testosterone gel therapy in elderly men revealed a higher incidence of MIs, atrial fibrillation, edema, and elevated blood pressure in the treatment group. Eldlerly men with low testosterone levels would be expected to have atherosclerosis. Heavy physical exertion can trigger the onset of acute myocardial infarction, particularly in people who are habitually sedentary., Beside the exercise testing performed in the TOM study, men generally have more motivation and energy with testosterone restoration and often greatly increase their physical activity, often taking on tasks they have been putting off for months. The starting dose of 100mg of this well-absorbed product (Testim 1%) was quite high as a starting dose for men of this age. Most of the adverse events recorded were due to the physiological stresses of a sudden increase in testosterone and even greater increase estradiol levels (not measured). Estradiol promotes plasma volume expansion and explains the peripheral edema and higher blood pressures seen in some of the men. In others, the increased in flow-mediated arterial dilation due to estradiol may have lowered blood pressure, producing orthostasis and syncope. Atrial fibrillation was increased too, probably as a result of increased T4-to-T3 conversion with higher testosterone levels. The fluid retention seen in some men was due to higher estradiol levels. The higher blood pressures were most likely also a short-term effect due to fluid retention. A retrospective study of veterans referred for coronary angiography showed a 30% higher rate of death, MI and stroke among men who were prescribed testosterone. 35% received bi-weekly intramuscular injections. However, serious errors were discovered in this study and The Androgen Society has petitioned the journal, JAMA, to retract the article.476253552825Another retrospective study involving men receiving testosterone prescription found an overall 30% increase in the low incidence of MI in the 90 days following a testosterone prescription. The higher incidence of MI was related to both history of heart disease and age. However, a similar retrospective cohort study found a protective effect of testosterone injections on MI, with the most benefit in those men with the higher risk of MI. Testosterone therapy reduced mortality by 50% over several years in a study of veterans. Mortality was twice as high in men with type 2 diabetes and low testosterone and was reduced by 50% in men treated with testosterone gel and injections. Lower testosterone levels within the reference range are associated with endothelial dysfunction in men. In the short-term, a superphysiological dose of testosterone enanthate by injection of 200mg/week produced a mild activation of the hemostatic system, but even at this dose, the activation markers returned to normal, and the new equilibrium did not appear to be prothrombotic.The administration of testosterone injections to female-to-male transsexuals has an anti-thrombotic effect. One study of men given testosterone injections showed an increased platelet aggregation response to a drug that mimics thromboxane A2. So testosterone may have both anti-thrombotic and pro-thrombotic effects. Testosterone Prevents DiabetesThere is a strong inverse relationship between insulin-resistant diabetes and testosterone levels. Low free and bioavailable testosterone concentrations in the normal range were associated with diabetes, independent of adiposity. Men with low testosterone levels have insulin resistance, testosterone treatment normalized insulin sensitivity and reduced body fat mass. It appears that the insulin-resistant diabetes with high insulin levels lowers testosterone production. Lower testosterone levels also worsen insulin sensitivity, and testosterone replacement with injections improves insulin sensitivity. Insulin resistance appears to increase estradiol levels in men relative to testosterone levels. Lower testosterone levels are associated with metabolic syndrome (essentially a form of insulin insensitivity or pre-diabetes). Higher testosterone levels are associated with a lower risk of insulin-resistant diabetes in men. Higher total and free testosterone levels are associated with higher insulin sensitivity. Over a 6-month period, transdermal TRT was associated with beneficial effects on insulin resistance, total and LDL-cholesterol, Lpa, and sexual health in hypogonadal men with type 2 diabetes and/or MetS. Effective TRT with injections in obese men with metabolic syndrome improved insulin resistance, reduced liver fat, reduce arterial stiffness, and increased lean (muscle) mass. It appears that higher testosterone levels help prevent metabolic syndrome. A literature review concluded that testosterone therapy may have a tremendous potential to slow or halt the progression of metabolic syndrome to overt diabetes or cardiovascular disease via beneficial effects on insulin regulation, lipid profile, and blood pressure. Testosterone replacement improves insulin sensitivity, reduces visceral fat mass, and lowers total cholelsterol and blood pressure. Up to 50% of men with type 2 diabetes have hypogonadism. Testosterone Does not Increase Prostate Cancer RiskContrary to popular opinion, scientific studies show that higher levels of testosterone at not associated with prostate enlargement or prostate cancer. Studies of men on testosterone replacement have consistently shown there is no increased risk of prostate cancer. In fact, the evidence is now clear: low testosterone levels increase the risk of prostate cancer! (See the new book "Testosterone for Life" by Dr. Abraham Morgentaler.) TRT does not cause prostate enlargement, it reduces prostate size in men with elevated LH levels. Testosterone replacement improves erectile function and alleviates lower urinary tract symptoms (urinary frequency, urgency, weak stream, etc.).A large prospective study showed no difference in testosterone levels between men who were and were not later diagnosed with prostate cancer. Benign prostatic hypertrophy is common in men as they age and it associated in studies with a higher estradiol/testosterone ratio., Men with prostate cancers that are more aggressive (higher Gleason score) have lower testosterone and estradiol levels then men with less aggressive cancers. A review of testosterone replacement showed that PSA levels, biopsy rates, and rates of prostate cancer diagnosis were higher in the treated group, but this is understandable given the fact that PSA rises with higher testosterone levels, prompting more biopsies in older man who have a high incidence of silent prostate cancer. Testosterone Prevents DementiaCalculated free testosterone concentrations were lower in men who developed Alzheimer disease, and this difference occurred before diagnosis. In rat neurons, testosterone reduces the secretion of Alzheimer’s beta-amyloid peptides. Androgen deprivation in mice increases beta-amyloid accumultation in the brain and reduced mental function—both of which are reversed with DHT treatment. Testosterone supplementation in older men improves working memory. A literature review concluded that testosterone loss maybe be a risk factor for cognitive decline and possibly for dementia. Higher testosterone levels in older men are associated with better cognitive performance. Testosterone treatment of men with mild-to-moderate Alzheimer’s disease and low testosterone levels produces improvements in cognition.The Importance of Estradiol in MenAnastrozole 1mg daily given to men with low testosterone raised testosterone levels while lowering estradiol slightly, yet even this small change led to a decline in bone mass.Testosterone is actually a pro-hormone and is beneficial to men because it is metabolized into estradiol and dihydrotestosterone. Higher testosterone levels leads to higher estradiol and DHT levels and effects. Estradiol in men comes from the aromatization of testosterone. Men have estradiol levels like those of a woman in the first two weeks of her cycle, but in the later two weeks a woman’s levels are much higher. Older men have less estradiol than when they were younger because their testosterone levels are low, but they still have have more estradiol than postmenopausal women! With intramuscular testosterone ester injections of 200mg/ml given to hypogonadal men, total testosterone and estradiol increase in the same proportion, maintain a normal T/E2 ratio. Total testosterone and estradiol rise 3-fold after a 200mg/ml injection. Free testosterone rises 4.5-fold. Testosterone decanoate injections normalize serum estradiol levels, although the decline in SHBG with testosterone replacement means that free estradiol levels rise proportionately more than total estradiol levels. Free estradiol levels do not rise in men with age, as many believe. Most studies show that free estradiol declines with age and this loss is associated with lower bone mass. but not as much as do free testosterone levels. This is probably due to the increase in subcutaneous fat in men with age, which increases the aromatization of testosterone to estradiol. Estradiol has the same beneficial effects in men as it does in women. It maintains bone mass and cognitive function. It protects against atherosclerosis, improves insulin sensitivity and reduces intra-abdominal fat. Estradiol levels have not been associated with mortality in men.The administration of DHT to men transdermally and decreases subcutaneous fat and increases hematocrit. Testosterone and estradiol levels declined with treatment, erectile function improved slightly. Interestingly, prostate weight and PSA levels did not change with treatment. Interestingly, in neither study did transdermal DHT improve well-being. It may be that the increase in estradiol levels with testosterone replacement is necessary for improved motivation and mood. Estradiol replacement certainly improves motivation, mood and sleep quality in women. Estradiol also stimulates increased growth hormone secretion. All relevant studies shown below with comments. First, my review of the Fallon Life Extension article on the dangers of high estradiol in men: Fallon's Life Extension article on estradiol’s dangers for men has many problems. This idea that estradiol is dangerous above a certain level is very common among hormone replacement practitioners. Fallon’s article admits that sufficient estradiol is clearly necessary for a man’s health but proposes that there is some upper level of estrogen--whether or not a man is on TRT--at which estrogen ceases to be beneficial and becomes deleterious. Fallon’s—or whoever the author—use of references is shoddy, he often quotes references whose implications are far different than what he asserts. For instance, he says that "symptoms of excess estrogen in aging men include the development of breasts, having too much abdominal weight, feeling tired, suffering loss of muscle mass, and having emotional disturbances. Many of these symptoms correspond to testosterone deficiency as well.41" The reference refers only to the symptoms of testosterone deficiency. There is no study existing that describes any symptoms due to high estradiol in men. Surely too much estradiol would cause breast enlargement, but there's no evidence for the other symptoms he mentions as being related to estradiol levels per se, neither have I seen any such evidence.Note that nothing in the article or its references touches on whether there are any adverse effects from higher total or free estradiol levels in men on testosterone replacement therapy, or on what estradiol levels should be on TRT. That is because no such evidence exists. There is an additional problem with any study of estradiol in men—usually only a total estradiol is done, not a free estradiol. So a man with high levels of sex-hormone-binding globulin (SHBG) may have a “high” total estradiol, but a “normal” free estradiol. Total estradiol is no more helpful than is total testosterone. The free or bioavailable estradiol and testosterone are what matter because there can be marked discrepancies in total and free levels in persons depending on their SHBG levels.?SHBG levels tend to rise with age, so producing higher total testosterone and estradiol levels but not higher free hormone levels. Fallon does mention the tremendous amount of evidence that estradiol is vital to men's health, but then quotes a few studies that found correlations between higher estradiol levels and certain health problems in older men, and presumes that the connection was causal--that the higher estradiol levels caused the pathology involved. He doesn't really seem to grasp the immense complexity of the hormonal system. Hormones affect everything, and everything affects hormones. Correlation surely does not prove causation in this case. Estradiol levels may be higher in older men do to their ill health, and so may be an innocent bystander, not the cause of the ill health. Fallon bases his upper limit recommendation for estradiol levels on a study of hip fractures in men. Fallon says, "Men with estradiol levels greater than 34.3 pg/mL had a slightly higher risk of hip fracture compared with those in the range of 18.2-34.2 pg/mL. This study helps confirm Life Extension’s recommended range for estrogen levels in aging men." What the article actually stated: "Incidence rates for hip fracture (per 1000 person-years) were 11.0, 3.4, and 3.9 for the low (2.0-18.1 pg/mL [7-67 pmol/L]), middle (18.2-34.2 pg/mL [67-125 pmol/L]), and high (> or =34.3 pg/mL [> or =126 pmol/L]) estradiol groups, respectively." Clearly there is no significant difference between the 3.4 and 3.9 incident rates for middle and higher estradiol levels, compared to the 11.0 rate for low estradiol. The study actually implies that once you are above a certain level of estradiol you are protected fully against fractures, higher levels do not add any additional protection. Fallon insinuates that the higher estradiol level somehow increased the men's risk for fracture. Such an effect was not seen, and would make no physiological sense.Fallon dismissed the Arnlov Framingham study that showed that higher baseline estradiol levels, and not testosterone levels, correlated with lower risk of cardiovascular disease in older men but not in younger men. He dismissed it even though it was a high-quality prospective study involving thousands of men. He stated that it went against all the other evidence that higher estradiol is associated with a higher risk of CVD. "All other evidence" is apparently the Mohamed study of 30 men with an acute MI who had higher estradiol and lower testosterone levels than controls. And the Phillips study that found higher estradiol levels in men who had had an MI. But, who knows what physiological effects occur during an acute MI and afterwards that may affect sex hormone metabolism? We need to know what their pre-MI hormonal status was. Another Phillips study found that low free testosterone, but not low or high estradiol, predicted finding coronary artery disease in men undergoing angiography. Fallon quotes a study showing higher estradiol levels but no difference in testosterone levels found in elderly men who went on to have a stroke, These are elderly men with very low testosterone levels, DHEAS levels, and growth hormone levels—all of which have anti-clotting effects as opposed to estradiol’s pro-clotting effects.—but doesn't mention the Jeppesen study that found lower testosterone levels but no difference in estradiol levels in men with acute stroke. In medicine, you can find one study to support almost any conclusion. One has to look at all available studies to begin to draw conclusion, not to mention one has make use of all other knowledge about the hormone, its effect in the body, etc. Fallon mentions the Tivesten study which found a correlation between higher estradiol levels and progression of carotid intima thickening, but he doesn't mention the Svartberg study where carotid artery intimal thickness (atherosclerosis) was associated with lower total testosterone levels and not at all with estradiol levels.?Some studies show lower testosterone and higher estradiol levels in men with diabetes and metabolic syndrome. but since estradiol improves insulin sensitivity, such studies imply not that estradiol causes diabetes, but that insulin resistance in diabetes or metabolic syndrome lowers testosterone and while increasing aromatization of testosterone to estradiol. Men who lack the aromatase enzyme have very low estradiol levels. Restoring estradiol in these men transdermally improve insulin sensitivity. Men with metabolic syndrome have lower testosterone levels and lower testosterone-to-estradiol ratios. Men with coronary heart disease have significantly lower free testosterone and total estradiol levels than men without heart disease.Fallon claims that estradiol levels rise with age, but fails to mention studies that show that estradiol declines with age in proportion to the decline in testosterone. like Van de Beld that show that total and free estradiol decline with age in healthy older men. Low levels of estradiol were associated with increased risk of death in older men, and the highest risk was found in men with both low testosterone and low estradiol.My own impression overall, looking over all the research I have seen so far, is that estradiol is critical for male health, and that when testosterone levels are too low, estradiol levels are also reduced adding to the many health problems caused by low testosterone. There are certain pathological conditions in which estradiol levels are higher in men--obesity and the metabolic syndrome--but it seems pretty clear that the higher estradiol levels are the result of the excess fat (aromatization) and metabolic abnormalities (high insulin?) that occur in those conditions. Lastly, there is a great deal of experience with male-to-female transsexuals. Oral estrogen therapy with the birth-control estrogen—ethinyl estradiol—had to be abandoned due to the increase in blood clots—just as in women. Transdermal or injected estradiol, however, has not been shown to cause any increase in blood clotting in women or in male-to-female transsexuals. They receive high, feminizing doses of estradiol. They have estradiol levels much higher than normal men, and they have little testosterone in their bodies. According to Fallon’s arguments, male-to-female transsexuals should be dying in large numbers. Yet published reports (Van Kestern above) state that their morbidity and mortality are not increased. So much for the dangers of higher estradiol levels in men. I have not mentioned that the “cure” for an estradiol above 34.5 for a man on testosterone replacement is an aromatase inhibitor (AI)—a drug that prevents the natural conversion of testosterone to estradiol. There are no long-term studies of AIs in men on testosterone. It is well known, however, that excessive AI will produce osteoporosis and other estrogen-deficiency problems in men. For certain, no drug should be prescribed for a hormone level that is not even known to be a problem! I do not believe that any man on testosterone replacement should take an AI for the purpose of lowering estradiol levels. How to Optimize Testosterone Levels and BenefitsReplacing testosterone to any point within the broad reference range is not enough. Treatment that produces higher levels within the range produces more improvement in symptoms and in metabolic parameters (lower cholesterol levels, greater reduction in waist circumference, lower SHBG). Trials that show little benefit of testosterone therapy in men with low levels often use inadequate dose or delivery methods. Dr. Lindner prefers testosterone cypionate or enanthate injections--self-administered subcutaneously--to the use of testosterone-containing creams or gels. The latter are very difficult to monitor. Subcutaneous fat contains the enzymes 5 alpha-reductase and aromatase that convert testosterone into DHT and estradiol, respectively. Therefore with application of testosterone to the skin, both DHT and estradiol are abnormally elevated relative to the increase in testosterone levels. The DHT/testosterone ratio is higher than normal, and the estradiol/testosterone ratio is double the normal ratio. As SHBG is unchanged, this is a marked increase in free estradiol to the top of the male range. Higher estradiol levels do produce a more pro-thrombotic state. This may explain the slight increase in absolute number of myocardial infarctions noted after men are prescribed testosterone gels. A testosterone patch (10mg/day) also raises serum DHT excessively, to level 3 times greater than men with similar testosterone levels from endogenous production. Another study comparing testosterone patches and gel found DHT/T ratios to be 2 to 3 times higher for the gel. Men treated with varying doses of injectable testosterone enanthate retained normal E2/T and DHT/T ratios at every dose level. Older men tended to aromatize T to E2 more vigorously and had higher free E2 levels and higher FE2/FT ratios than younger men. Testosterone undecanoate injections produce normal testosterone, DHT, and estradiol levels. Testosterone injections produce proportional increases in both testosterone and estradiol levels—maintaining the normal estradiol/testosterone ratio.Testosterone patches do produce more physiological T/DHT and T/E2 ratios than testosterone gels.DHT and DHT/T rations are 2 to 3 times higher with testosterone gel. Testosterone patches (5mg/day) produced a 75% increase in testosterone levels and no increase in estradiol levels. Scrotal testosterone patches produce a 200% increase in testosterone and DHT levels with only a 40% increase in estradiol levels. Narharci 2/23Normally, the testes produce 4–10 milligrams (mg) of testosterone daily.With transdermal gel, 9-14% of T applied is bioavailableSteady state T levels were achieved 48-72 h after first application of the gel.After first application of T gel to one site, serum T levels rose rapidly to 2.4 times the baseline concentration and into the normal range within 30 min. The levels continued to slowly rise throughout the day to 4.2-fold of Cbaseline at 24 h. 100mg/day excessive for most males. The Journal of Clinical Endocrinology & Metabolism Vol. 85, No. 3 964-969Free T measurement by equilibrium dialysis is considered the gold standard for the measurement of free T. The Journal of Clinical Endocrinology & Metabolism Vol. 89, No. 2 520-524DHT therapy studies: Kunelius 2002, Ly 2001“The assumption that treatment with T is adequate when achieved plasma levels of T are within the reference range is no longer tenable. Some androgen-dependent biological functions require higher plasma T levels than others, and, moreover, these thresholds differ among men.” (Saad, 2009)DHT is often high-normal or elevated in men with low testosterone as the body tries to compensate for testosterone deficiency with increase 5-alpha reductase activity. (Gooren, 2008)Hepatic adenomas associated with oral anabolic steroids esp. oxymetholone. One report only of an adenoma in a patient on testosterone enanthate injections. (Carasco, 1985) No liver changes observerd in seen in 82 autopsies of men on testosterone enanthate injections. (Saheb 1980)Problems caused by artificial anabolic steroids have no relevance to bioidentical testosterone restoration. Oral methyltestosterone lowers serum testosterone to very low levels, correlating to poorer cognitive function, and lower free T4, correlating to anger, violent feelings, and irritability. It and other oral 17-alkylated testosterone drugs produced liver disease and tumors; testosterone ester injections do not. Here again, as with the female hormones, lay persons and most medical professionals still think that the problems caused by artificial hormones substitutes also occur with natural, physiological hormone restoration. "Roid rage" and liver disease are caused by oral 17- alkylated testosterone substitutes and other non-bioidentical anabolic steroids, usually taken in doses that are many times greater than "replacement" doses.Free testosterone peaks on days 2 to 3 after an injection, and non-SHBG bound testosterone on days 2 to 7 after injection. By day 14, testosterone levels return to pre-treatment. I therefore have chosen have blood drawn on day 5 after a weekly injection as a best estimate of average testosterone levels throughout the week. It is often claimed that TRT causes or worsens sleep apnea, but a reviewer found little support for this contention. A recent study of effective TRT in obese men with sleep apnea found a slight worsening of sleep apnea at 6 weeks but none at 18 weeks. A mechanism for this effect is lacking.The hemoglobin and hematocrit (H&H) levels in men are strongly affected by testosterone levels. The H&H are lower in men with lower free testosterone levels, and reliably rise with testosterone supplementation. Testosterone increases erythropoietin secretion, recalibrating its set point in relation to the H&H. The increase in H&H is a beneficial effect, increasing oxygen delivery to the tissues and improving performance. Athletes attempt to achieve higher H&H levels by training at high altitudes where the lower partial pressure of oxygen leads to a stimulation of erythropoesis and higher H&H. In men who are chronically oxygen-deprived due to sleep apnea or lung disease, restoring testosterone even to normal levels can cause H&H to rise above the population ranges. This is a pure erythrocytosis—and excess of red blood cell mass only. Platelets and coagulation are not affected. This is technically a form of polycythemia, but it is not polycythemia vera, a cancer of the bone-marrow causing excessive production of all blood cells including platelets and white blood cells. In persons with polycythemia vera, hematocrit levels up to 55% were not associated with thrombotic events or mortality. ................
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