Across all studies, men had a mean baseline testosterone of 323 ng/dL, mean age of 59.9 years, and were followed for an average 34 weeks, during which time they were administered either a placebo or one of several testosterone modalities. Conversely, a population-based retrospective case-control study utilizing a UK clinical database of 19,215 patients with confirmed VTE showed that there was increased risk of VTE in the first 6 months of testosterone therapy. A study by Pastuszak et al. (2015)355 found a significant increase in biochemical recurrence in high-risk patients who received testosterone therapy after RT or RT/ADT. Available studies are retrospective in nature but have suggested that post-RT patients (with or without ADT exposure) placed on testosterone therapy do not experience recurrence of prostate cancer. 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 Evaluation and Management of Testosterone Deficiency AUA Guideline provides guidance to the practicing clinician on how to diagnose, treat and monitor the adult male with testosterone deficiency. It is concluded that the various handling procedures of blood or plasma have no significant effect on T and Adione levels. Men with total testosterone level 315 ng/dL declined from 100% at 4 weeks to 86%, 75%, and 14% by 12, 20, and 24 weeks, respectively. One study reported comparative pharmacokinetics between IM testosterone enanthate (250 mg every 3 weeks) and IM testosterone undenaconate (1,000 mg every 9 weeks, a dosage that is only available outside the United States).440 Results demonstrated that IM testosterone enanthate achieved trough levels of 239 ng/dL compared to 470 ng/dL with IM testosterone undecanoate at the end of the 10-week cycle. Given the half-life of approximately seven days, it is reasonable to obtain testosterone levels four weeks after starting therapy. If insufficient testosterone levels are achieved with one topical agent, including with dose adjustments, substitution with another topical agent is a viable treatment strategy.420 However, compared to other agents, short-acting injections can result in longer times in the supra-therapeutic and sub-therapeutic ranges, which may impact overall efficacy and rates of adverse events. Likewise, there might be value in defining the trough level (measured prior to injection on day one) to ensure patients remains therapeutic throughout the entire cycle. The best time to obtain monitoring blood tests for IM testosterone has not been definitively established. In general, smaller dosages at more frequent intervals are preferred over high, less frequent administrations to limit the duration of time spent outside (above or below) the normal reference range. Mean testosterone values over a 7-day time period were 1,659, 896, and 422 ng/dL for IM testosterone SQ 100, and SQ 50, respectively. Other limitations included the possible subjective nature in reporting some adverse events.Conversely, the Shores, 367 Muraleedharan,233 and Baillargeon373 studies determined that there was no increased risk of MACE in men who were on testosterone therapy. Two of the retrospective studies included in the FDA review pointed to an increased risk of cardiovascular events in men on testosterone therapy. Although the committee reviewing the evidence concluded that there was not enough data to definitively state that testosterone therapy posed a significant cardiovascular risk, the FDA nonetheless required testosterone product manufacturers to add information to the labeling about a possible increased risk of myocardial infarction and cerebrovascular accidents in patients using testosterone therapy. Following inverse propensity treatment weighting, the cumulative percentage of patients who met the primary outcome 3 years post-angiography was 25.7% on treatment and 19.9% in the placebo group. In the testosterone therapy group, the raw data revealed a 2% myocardial infarction rate and a 3% cerebrovascular accident rate compared to 6% and 6%, respectively, in those patients not receiving testosterone. Over a mean duration of 27.5 months, 1,223 men received testosterone therapy, and 7,486 were placed on placebo. Two of the trials and one meta-analysis pointed to an increased risk of cardiovascular events,363, 364, 366 two revealed no cardiovascular risk,233, 367 and one was neutral with respect to risk.373 The Corona meta-analysis,372 which showed that there was no increased risk of cardiovascular events, was not officially reviewed but was taken into consideration in the final analysis. However, the FDA added a warning to testosterone product labeling after reviewing five observational studies and two meta-analyses of RCTs that examined the effects of testosterone therapy on MACE.
