Of the outcomes included in the protocol of this systematic review, data were available on quality of life (QoL), sexual function, cardiovascular events, anemia, bone health, insulin resistance, cardiovascular risk factors, mood, cognitive function, body composition, and numerous adverse events. Clinicians should inform testosterone deficient patients that low testosterone is a risk factor for cardiovascular disease. The use of validated questionnaires is not currently recommended to either define which patients are candidates for testosterone therapy or to monitor symptom response in patients on testosterone therapy. Clinicians should use a total testosterone level below 300 ng/dL as a reasonable cut-off in support of the diagnosis of low testosterone.
Acute illnesses should be considered when measuring testosterone levels, the presence of which can affect the accuracy of the test and lead to artificially decreased testosterone measurements. To ensure accuracy and precision, it is necessary to obtain at least two serum total testosterone measurements in an early morning fashion to diagnose patients with low testosterone. One strategy is to further evaluate patients using adjunctive tests, which might strengthen an argument for a short-term trial of testosterone therapy. Establishing total testosterone thresholds for a diagnosis of testosterone deficiency is challenging considering the heterogeneity that exists in the testosterone deficiency literature. However, as the testosterone literature uses absolute values to define low testosterone, the absolute value is ultimately the most important factor to determine whether patients may expect to achieve benefits with testosterone therapy. Evidence strength refers to the body of evidence available for a particular question and includes not only individual study quality but consideration of study design, consistency of findings across studies, adequacy of sample sizes, and generalizability of samples, settings, and treatments for the purposes of the guideline.
The European Male Aging Study (EMAS)8 studied 3,369 men (mean age 59 years) and culled data on their sexual, physical, and psychological symptoms along with morning total testosterone measurements. Point estimates that measure the difference in testosterone levels between men with and without ED may appear statistically significant, but these estimates are not always clinically meaningful. A challenge in making the diagnosis of testosterone deficiency is that many of the symptoms reported by patients are non-specific and might be related to conditions other than low testosterone. Total testosterone  absence of signs and/or symptoms increases the likelihood of making a false diagnosis and reduces the potential benefit of testosterone therapy.
Ultimately, the AUA and the Testosterone Panel were committed to creating a Guideline that ensures that men in need of testosterone therapy are treated effectively and safely. The goals of this document are to (i) guide clinicians in how to assess patients for testosterone deficiency and manage them with testosterone products, and (ii) educate clinicians in key areas of testosterone in which many clinicians are deficient (e.g., interpreting the testosterone literature, understanding testosterone laboratory testing). The explosion in the use of testosterone in the past decade is multifactorial in its etiology, including the increased use of direct-to-consumer advertising, which has resulted in greater patient knowledge and demand; relaxation of the indications for testosterone prescribing by clinicians; and the establishment of clinical care centers devoted to men's health, testosterone treatment, and anti-aging strategies. Clinicians should discuss the risk of transference with patients using testosterone gels/creams. Exogenous testosterone therapy should not be prescribed to men who are currently trying to conceive. All men with testosterone deficiency should be counseled regarding lifestyle modifications as a treatment strategy.
There are conflicting results in the literature as to whether testosterone therapy has a significant impact on these symptoms. Men who seek medical care for possible testosterone therapy often present with non-specific symptoms, such as low energy and fatigue, which can be manifestations of other conditions, such as chronic stress, chronic fatigue, and depression. The rate of remission was also higher in a statistically significant manner among dysthymic men receiving testosterone therapy (53%) compared to placebo (19%).317, 318
Twelve studies (3 in HIV-positive men) evaluated testosterone supplementation in men with a diagnosis of depression or dysthymia (sometimes also called, "minor depression"), 1 study evaluated the use of testosterone in men with schizophrenia, and 2 studies were conducted in men with Alzheimer disease or cognitive impairment. Another study found that testosterone treatment had no effect on the Hospital Anxiety Depression score (HADS) in men with testosterone ≤8.0 nM but improved the depression subset of the HADS in men with testosterone of 8.1–12 nM. A study in non-depressed men with metabolic syndrome reported an improvement in the BDI in testosterone-treated compared to placebo-treated subjects. Seventeen of 29 studies reported no effect of testosterone treatment on personality, psychological well-being, or mood.22, 24, 38, 59, 63, 85, 104, 113–121 Seven of 17 studies had a Jadad score of 4 or 5. Two studies (Jadad score 3 and 5) reported a decrease in anxiety after testosterone treatment.45, 112 Another study showed no effect of IM testosterone enanthate on ejection fraction, although there was an improvement in a Doppler-based myocardial performance index. Intramuscular (IM) testosterone treatment for 12 weeks improved exercise capacity and reduced heart failure symptom scores without identifiable effects on left ventricular size or ejection fraction (EF). There was a decreased incidence of silent MI with testosterone treatment in 1 study. The remaining eight studies evaluated treatments of 2 to 24 weeks in duration.1, 3, 10, 11, 13–17 The 3 studies that looked at time to ST-segment depression found a benefit of testosterone supplementation.1, 14, 16|Where possible, clinicians should use LCMS to measure total testosterone levels to maximize accuracy and limit CV between tests in men undergoing testing, particularly in men with very low total testosterone levels. Testosterone levels should be measured every 6-12 months while on testosterone therapy. Clinicians should measure an initial follow-up total testosterone level after an appropriate interval to ensure that target testosterone levels have been achieved. Clinicians should adjust testosterone therapy dosing to achieve a total testosterone level in the middle tertile of the normal reference range. Patients with testosterone deficiency and a history of prostate cancer should be informed that there is inadequate evidence to quantify the risk-benefit ratio of testosterone therapy. Prior to offering testosterone therapy, clinicians should measure hemoglobin and hematocrit and inform patients regarding the increased risk of polycythemia. Replenishing deficient testosterone levels through therapy may help restore these functions to optimal levels over time.}