Thus, a patient is considered testosterone deficient and a candidate for testosterone therapy only when he meets both criteria. 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). Clinicians should discuss the risk of transference with patients using testosterone gels/creams. Testosterone therapy should not be commenced for a period of three to six months in patients with a history of a cardiovascular events. Patients should be informed that there is no definitive evidence linking testosterone therapy to a higher incidence of venothrombolic events. The long-term impact of exogenous testosterone on spermatogenesis should be discussed with patients who are interested in future fertility. Patients should be informed that the evidence is inconclusive whether testosterone therapy improves cognitive function, measures of diabetes, energy, fatigue, lipid profiles, and quality of life measures. 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. A systematic review of the published literature was conducted to answer these key questions and provide the evidence base for the guideline. Hypogonadism has more recently been used interchangeably with the idea of low testosterone production alone. Commercially manufactured testosterone products should be prescribed rather than compounded testosterone, when possible. Meta-analyses that are limited to only including RCTs may be restricted to a small number of studies and relevant studies may be excluded that could provide sufficient power to make alternative conclusions. For example, outcomes of meta-analyses using RCTs alone are generally more robust than those that also include cohort studies. As with all AUA guideline documents, recommendations are based where possible on data extracted from the evidence report, which was generated by methodologists from Mayo Clinic. Patients who are on long-acting SQ pellets require two separate assessments of testosterone to determine the dose and frequency required. As with short-acting IM testosterone injections, the general recommendation is mid-cycle testing, after equilibration, and halfway between the first two 10-week injections. At this time, there is no definitive evidence indicating what the optimal time interval should be between the two separate tests. Intra-individual testosterone variability is significant. Total testosterone values obtained at 4p.m. Although direct measurement of free testosterone has a generally good correlation with equilibrium dialysis, it is not reliable because of high CV. Clinicians should discuss the cessation of testosterone therapy three to six months after commencement of treatment in patients who experience normalization of total testosterone levels but fail to achieve symptom or sign improvement. PSA secretion is an androgen dependent phenomenon, and the rise of PSA levels in patients on testosterone therapy is primarily dependent upon baseline total testosterone levels. Two studies145, 146 included in the evidence report that was developed in the support of this guideline suggest a link between radiation (in rectal cancer and prostate cancer patients) and low testosterone levels, however the studies are limited by heterogeneity in study populations, heterogeneity in radiation delivery, and the presence of confounders such as chemotherapy exposure. Although confounders were accounted for in the analysis, concurrent medications that may have reduced the risk for myocardial infarction or other testosterone therapies used outside of the study protocol were not controlled for or assessed.Since the FDA warning in 2015, other studies have failed to demonstrate a risk of cardiovascular events in patients on testosterone therapy. In a 12-week study in 82 men, 72.6% of patients achieved a total testosterone concentration within the physiological range at steady state.434 Men treated with the agent were compared to a group of patients given 5 mg of a testosterone gel formulation, and no differences in mean testosterone serum levels were observed between the two groups.435 The study showed 92% of buccal versus 83% of gel patients achieved testosterone levels in the physiologic range. In the uncommon circumstance where men have prior available off-therapy testosterone laboratory data considered reliable (early morning testing, appropriate assay), clinicians may consider titrating testosterone therapy dosing to return patients to their 'baseline' total testosterone level. The goal of testosterone therapy is the normalization of total testosterone levels combined with improvement in symptoms or signs. Three of these men were brachytherapy patients alone, did not cease testosterone therapy, and their PSA values eventually decreased. Overall, seven studies reported no benefits on QoL in men using testosterone therapy compared to placebo,199, 205, 212, 225, 226, 230, 303, 318 while five studies demonstrated improvements.203, 317, 319, 328, 329 The impact of testosterone therapy on QoL in men with testosterone deficiency is challenging to quantify due to variable study methodology and inherent limitations with standardized questionnaires. However, when patients were requested to assess their global impression of change regarding energy level, men receiving testosterone were significantly more likely to rate changes as a little or much better compared to placebo (approximately 15% more in testosterone cohort). Patients with anemia, both unexplained and explained, can increase their Hb and/or Hct levels while on testosterone therapy.
