While all products contain the same medication (testosterone), each product and modality has distinct pharmacokinetic and application attributes based on the excipient agents and the permeator components. Expert Opinion refers to a statement, achieved by consensus of the Panel, that is based on members' clinical training, experience, knowledge, and judgment for which there is no evidence. When body of evidence strength Grade C is used, there is uncertainty regarding the balance between benefits and risks/burdens, alternative strategies may be equally reasonable, and better evidence is likely to change confidence. When body of evidence strength Grade B is used, benefits and risks/burdens appear balanced, the best action also depends on individual patient circumstances, and better evidence could change confidence. When body of evidence strength is Grade A, the statement indicates that benefits and risks/burdens appear balanced, the best action depends on patient circumstances, and future research is unlikely to change confidence. Body of evidence strength Grade C in support of a Strong or Moderate Recommendation indicates that the statement can be applied to most patients in most circumstances but that better evidence is likely to change confidence. Body of evidence strength Grade B in support of a Strong or Moderate Recommendation indicates that the statement can be applied to most patients in most circumstances but that better evidence could change confidence. Topical testosterone preparations (e.g., gels, creams, liquids) have the potential to result in transference to others. Given the availability of other approved testosterone therapies, the use of 17-alpha-akylated androgens is not appropriate. The general trend indicated that higher doses of testosterone were more likely to result in azoospermia than lower doses, however a dose-response effect was not consistently seen. Normal sperm production depends on a functionally intact hypothalamic-pituitary-gonadal axis with normal secretion of pituitary LH and FSH to support intratesticular testosterone production and spermatogenesis. While definitive age-specific reference ranges do not exist, some data suggest that patient age may play a role in setting therapeutic ranges, at least in the elderly population. The trials were not powered to measure MACE as a primary endpoint (outcome measures included efficacy or product, muscle strength, AMS scores, and sex drive); cardiac-related events were categorized as adverse outcomes. There were inconsistently defined end points to categorize severe cardiac events, which included 'softer' endpoints (e.g., edema, tachycardia, hypertension) along with myocardial infarction and stroke.194 The statistical analysis did not account for confounding factors; the duration of follow-up varied widely, from 12 weeks to 3 years; and many of the trials were not powered to detect cardiac events as primary endpoints, rather they were catalogued as adverse outcomes. In the majority of testosterone therapy protocols, the male physical characteristics can be seen in almost all users after 6 months of therapy, and the maximum virilization effects are usually achieved after 3 to 5 years of regular use of the hormone. Primary care physicians are increasingly involved in the initiation and management of testosterone therapy for this population. Development of polycythemia during treatment should lead to cessation of therapy, lowering of the dose, or switching to a lower-risk formulation to avoid increased risk of myocardial infarction, stroke, and venous thromboembolism. Use of supplemental testosterone has been shown to cause a small increase in prostate-specific antigen (PSA) levels,52 but the significance of this increase is questionable. The effects of testosterone therapy on cardiovascular health remain unclear. In February 2016, the first results from the Testosterone Trials sponsored by the National Institutes of Health were published.14 This set of seven randomized controlled trials assessing sexual function, vitality, physical function, cognitive function, anemia, bone density, and cardiovascular health represents the largest, most rigorously conducted study of the benefits of testosterone therapy for older men. Based on postmarket reports, in 2014 the FDA required manufacturers of testosterone products to add a warning to the drug label about the risk of venous thromboem-bolism.56 Subsequently, a large case-control study and another large retrospective cohort study found no evidence of increased venous thromboembolism risk.57,58 There also does not appear to be a significant increase in lower urinary tract symptoms with testosterone therapy, although most studies have excluded men with severe lower urinary tract symptoms at baseline.54 Because prostate cancer can be stimulated by testosterone, testosterone therapy is contraindicated in patients with known or suspected prostate cancer. No randomized controlled trial has demonstrated decreased cardiovascular events or mortality with testosterone therapy. Although the findings of the TOM trial are concerning, this study enrolled a high-risk population, and its findings may not be generalizable to most men being considered for testosterone therapy. The EAU does not specify a time frame, but notes that acute CV events are a relative contraindication.6,14 These patients may also benefit from referral to a urologist or endocrinologist/andrologist (Figure 2).1,42 For pellets, concentrations should be assessed at the end of the dosing interval and adjusted to achieve serum testosterone concentrations in the mid-to-normal range. Additionally, they should be counseled about the potential for exogenous testosterone to suppress hypothalamic-pituitary-gonadal (HPG) axis function and thereby impair intratesticular testosterone production, spermatogenesis, and fertility (Table 2).1,4,19–21 FIf there is clinical indication of hypopituitarism or sella abnormality on imaging, evaluation of other pituitary hormones (eg, free thyroxine, morning cortisol, and adrenocorticotropic hormone stimulation test if clinical hypocortisolism is suspected) should be performed. BhasinS,SaferJ,TangprichaV.Thehormonefoundation’spatientguideto the endocrine treatment of transsexual persons. A cross-sectional study.
