What about basic Test?!?!?! 
Testosterone dose-response relationships in healthy young men.
Abstract
Testosterone increases muscle mass and strength and regulates other physiological processes, but we do not know whether testosterone effects are dose dependent and whether dose requirements for maintaining various androgen-dependent processes are similar. To determine the effects of graded doses of testosterone on body composition, muscle size, strength, power, sexual and cognitive functions, prostate-specific antigen (PSA), plasma lipids, hemoglobin, and insulin-like growth factor I (IGF-I) levels, 61 eugonadal men, 18-35 yr, were randomized to one of five groups to receive monthly injections of a long-acting gonadotropin-releasing hormone (GnRH) agonist, to suppress endogenous testosterone secretion, and weekly injections of 25, 50, 125, 300, or 600 mg of testosterone enanthate for 20 wk. Energy and protein intakes were standardized. The administration of the GnRH agonist plus graded doses of testosterone resulted in mean nadir testosterone concentrations of 253, 306, 542, 1,345, and 2,370 ng/dl at the 25-, 50-, 125-, 300-, and 600-mg doses, respectively. Fat-free mass increased dose dependently in men receiving 125, 300, or 600 mg of testosterone weekly (change +3.4, 5.2, and 7.9 kg, respectively). The changes in fat-free mass were highly dependent on testosterone dose (P = 0.0001) and correlated with log testosterone concentrations (r = 0.73, P = 0.0001). Changes in leg press strength, leg power, thigh and quadriceps muscle volumes, hemoglobin, and IGF-I were positively correlated with testosterone concentrations, whereas changes in fat mass and plasma high-density lipoprotein (HDL) cholesterol were negatively correlated. Sexual function, visual-spatial cognition and mood, and PSA levels did not change significantly at any dose. We conclude that changes in circulating testosterone concentrations, induced by GnRH agonist and testosterone administration, are associated with testosterone dose- and concentration-dependent changes in fat-free mass, muscle size, strength and power, fat mass, hemoglobin, HDL cholesterol, and IGF-I levels, in conformity with a single linear dose-response relationship. However, different androgen-dependent processes have different testosterone dose-response relationships.
Testosterone Replacement Therapy and Mortality in Older Men.
Abstract
While US testosterone prescriptions have tripled in the last decade with lower trends in Europe, debate continues over the risks, benefits and appropriate use of testosterone replacement therapy (TRT). Several authors blame advertising and the availability of more convenient formulations, whilst others have pointed out that the routine testing of men with erectile dysfunction (ED) (a significant marker of cardiovascular risk) and those with diabetes would inevitably increase the diagnosis of hypogonadism and lead to an increase in totally appropriate prescribing. They commented that this was merely an appropriate correction of previous under-diagnosis and under-treatment in line with evidence based guidelines. It is unlikely that persuasive advertising or convenient formulations could grow a market over such a sustained period if the treatment was not effective. Urologists and primary care physicians are the most frequent initiators of TRT usually for ED. Benefits are clearly established for sexual function, increase in lean muscle mass and strength, mood and cognitive function, with a possible reduction in frailty and osteoporosis. There remains no evidence that TRT is associated with increased risk of prostate cancer or symptomatic benign prostatic hyperplasia, yet the decision to initiate and continue therapy is often decided by urologists. The cardiovascular issues associated with TRT have been clarified by recent studies showing that therapy associated with clear increases in serum testosterone levels to the normal range is associated with reduced all-cause mortality. Studies reporting to show increased risk have been subject to flawed designs with inadequate baseline diagnosis and follow-up testing. Effectively, they have compared non-treated patients with under-treated or non-compliant subjects involving a range of different therapy regimes. Recent evidence suggests long-acting injections may be associated with decreased cardiovascular risk, but the transdermal route may be associated with potentially relatively greater risk because of conversion to dihydrotestosterone by the effect of 5-alpha reductase in skin. The multiple effects of TRT may add up to a considerable benefit to the patient that might be underestimated by the physician primarily concerned with his own specialty. In a response to concerns about the possible risks associated with inappropriate prescribing expressed by Public Citizen, the Food and Drug Administration (FDA) published a complete refutation of all the concerns, only to issue a subsequent bulletin of concern over inappropriate use, whilst confirming the benefits in treating men with established testosterone deficiency. No additional evidence was provided for this apparent change of opinion, but longer term safety data on testosterone products were strongly suggested. In contrast, the European Medicines Agency (EMA), in November 2014, concluded that "there is no consistent evidence of increased cardiovascular risk with testosterone products". This paper explores the most recent evidence surrounding the benefits and risks associated with TRT.
KEY POINTS
There is a high level of evidence that hypogonadism is associated with increased all-cause mortality and reduced quality of life.
A large body of evidence shows that testosterone replacement therapy according to expert guidelines is safe and effective for men suffering from testosterone deficiency.
Emerging evidence shows that testosterone replacement therapy in hypogonadal men may reduce all-cause mortality.
Recent studies suggesting that testosterone replacement therapy may increase cardiovascular risk are severely flawed and do not exclude the possibility that the increased risk is related to hypogonadism and not the testosterone treatment.
Effects of Testosterone Administration for 3 Years on Subclinical Atherosclerosis Progression in Older Men With Low or Low-Normal Testosterone Levels: A Randomized Clinical Trial.
Abstract
IMPORTANCE:
Testosterone use in older men is increasing, but its long-term effects on progression of atherosclerosis are unknown.
OBJECTIVE:
To determine the effect of testosterone administration on subclinical atherosclerosis progression in older men with low or low-normal testosterone levels.
DESIGN, SETTING, AND PARTICIPANTS:
Testosterone's Effects on Atherosclerosis Progression in Aging Men (TEAAM) was a placebo-controlled, double-blind, parallel-group randomized trial involving 308 men 60 years or older with low or low-normal testosterone levels (100-400 ng/dL; free testosterone <50 pg/mL), recruited at 3 US centers. Recruitment took place between September 2004 and February 2009; the last participant completed the study in May 2012.
INTERVENTIONS:
One hundred fifty-six participants were randomized to receive 7.5 g of 1% testosterone and 152 were randomized to receive placebo gel packets daily for 3 years. The dose was adjusted to achieve testosterone levels between 500 and 900 ng/dL.
MAIN OUTCOMES AND MEASURES:
Coprimary outcomes included common carotid artery intima-media thickness and coronary artery calcium; secondary outcomes included sexual function and health-related quality of life.
RESULTS:
Baseline characteristics were similar between groups: patients were a mean age of 67.6 years; 42% had hypertension; 15%, diabetes; 15%, cardiovascular disease; and 27%, obesity. The rate of change in intima-media thickness was 0.010 mm/year in the placebo group and 0.012 mm/year in the testosterone group (mean difference adjusted for age and trial site, 0.0002 mm/year; 95% CI, -0.003 to 0.003, P = .89). The rate of change in the coronary artery calcium score was 41.4 Agatston units/year in the placebo group and 31.4 Agatston units/year in the testosterone group (adjusted mean difference, -10.8 Agatston units/year; 95% CI, -45.7 to 24.2; P = .54). Changes in intima-media thickness or calcium scores were not associated with change in testosterone levels among individuals assigned to receive testosterone. Sexual desire, erectile function, overall sexual function scores, partner intimacy, and health-related quality of life did not differ significantly between groups. Hematocrit and prostate-specific antigen levels increased more in testosterone group.
CONCLUSIONS AND RELEVANCE:
Among older men with low or low-normal testosterone levels, testosterone administration for 3 years vs placebo did not result in a significant difference in the rates of change in either common carotid artery intima-media thickness or coronary artery calcium nor did it improve overall sexual function or health-related quality of life. Because this trial was only powered to evaluate atherosclerosis progression, these findings should not be interpreted as establishing cardiovascular safety of testosterone use in older men.
Key Points
The results of the 3-year long JAMA study were reported in the abstract as mainly neutral, concluding that testosterone therapy did not affect markers of atherosclerosis (intima-media thickness and coronary artery calcium score), nor improve overall sexual function or health-related quality of life.
As expected, hematocrit and PSA levels increased more in the testosterone group, but values stayed largely within the normal range. This within-normal-range increase is a physiological response to testosterone therapy.
Two important positive outcomes, which were not mentioned in the study abstract, were:
The number of subjects reporting adverse events or serious adverse events did not differ between testosterone and placebo groups. This confirms that testosterone therapy is safe, even in men over 60 years of age.
In men not taking statins, one marker of atherosclerosis (coronary artery calcium) was significantly lower in the testosterone group than in the placebo group.
An important problem of the study, also not mentioned in the abstract, was that testosterone levels declined over time, despite dose-adjustments aiming to achieve testosterone levels between 500 and 900 ng/dL. This suggests low adherence and sub-optimal testosterone therapy.
Normalization of Testosterone Level Is Associated With Reduced Incidence of Myocardial Infarction and Mortality in Men
Abstract
Aims There is a significant uncertainty regarding the effect of testosterone replacement therapy (TRT) on cardiovascular (CV) outcomes including myocardial infarction (MI) and stroke. The aim of this study was to examine the relationship between normalization of total testosterone (TT) after TRT and CV events as well as all-cause mortality in patients without previous history of MI and stroke.
Methods and results We retrospectively examined 83 010 male veterans with documented low TT levels. The subjects were categorized into (Gp1: TRT with resulting normalization of TT levels), (Gp2: TRT without normalization of TT levels) and (Gp3: Did not receive TRT). By utilizing propensity score-weighted Cox proportional hazard models, the association of TRT with all-cause mortality, MI, stroke, and a composite endpoint was compared between these groups. The all-cause mortality [hazard ratio (HR): 0.44, confidence interval (CI) 0.42–0.46], risk of MI (HR: 0.76, CI 0.63–0.93), and stroke (HR: 0.64, CI 0.43–0.96) were significantly lower in Gp1 (n = 43 931, median age = 66 years, mean follow-up = 6.2 years) vs. Gp3 (n = 13 378, median age = 66 years, mean follow-up = 4.7 years) in propensity-matched cohort. Similarly, the all-cause mortality (HR: 0.53, CI 0.50–0.55), risk of MI (HR: 0.82, CI 0.71–0.95), and stroke (HR: 0.70, CI 0.51–0.96) were significantly lower in Gp1 vs. Gp2 (n = 25 701, median age = 66 years, mean follow-up = 4.6 years). There was no difference in MI or stroke risk between Gp2 and Gp3.
Conclusion In this large observational cohort with extended follow-up, normalization of TT levels after TRT was associated with a significant reduction in all-cause mortality, MI, and stroke.
KEY POINTS
In men who have low total testosterone levels but no previous heart attack or stroke, testosterone therapy is associated with decreased risks of heart attack, stroke, and all-cause mortality during a long-term follow-up of up to 14 years.
Compared to non-treated men, testosterone treated men who achieved normalization of their testosterone levels had a reduction in heart attack, stroke and all-cause mortality by 24%, 36% and 56%, respectively.
Compared to non-treated men, testosterone treated men who failed to achieve normalization of their testosterone levels did not have a reduction in heart attack or stroke, and had significantly less benefit on mortality risk.
Testosterone therapy should aim for doses resulting in normalization of total testosterone level, as this is a prerequisite to achieve a reduction in heart attack and stroke.
