Editing Testosterone Deficiency (2018) (section)

===== Inconclusive =====
*'''<span style="color:#ff0000">Cardiovascular events'''
** '''<span style="color:#ff0000">Low testosterone is a risk factor for cardiovascular disease (myocardial infarction, stroke, and possible cardiovascular-related mortality).'''
*** '''It cannot be stated definitively whether testosterone therapy increases or decreases the risk of cardiovascular events''' (e.g., myocardial infarction, stroke, cardiovascular-related death, all-cause mortality).
****'''<span style="color:#ff00ff">TRAVERSE 2023</span>''' (new since publication of AUA guidelines)
*****'''Population: 5246 males aged 45-80 who had preexisting or a high risk of cardiovascular disease and who reported symptoms of hypogonadism and had two fasting testosterone levels < 300 ng/dL'''
*****Randomized to daily transdermal testosterone (dose adjusted to maintain normal testosterone levels) or placebo gel
*****'''Outcomes'''
******'''Primary: first occurrence of any component of a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke'''
******Secondary: first occurrence of any component of the composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization
*****'''Results'''
******Mean duration of treatment: 27 months
******Mean follow-up: 33 months
******'''No significant difference in primary or secondary outcomes'''
******Higher incidence of atrial fibrillation, acute kidney injury, and pulmonary embolism in testosterone group
****[https://pubmed.ncbi.nlm.nih.gov/37326322/ Lincoff, A. Michael, et al.] "Cardiovascular Safety of Testosterone-Replacement Therapy." ''New England Journal of Medicine'' (2023).
**'''No definitive evidence linking testosterone therapy to a higher incidence of venothrombolic events'''
* '''Evidence is inconclusive whether testosterone therapy improves cognitive function, energy, fatigue, measures of diabetes, lipid profiles, and quality of life measures'''
** Despite the absence of definitive evidence, the Panel recommends that patients with these symptoms be counseled regarding the possibility of improvement on testosterone therapy.
* '''<span style="color:#ff0000">Prostate cancer''' 
** '''<span style="color:#ff0000">No definitive evidence linking testosterone therapy and prostate cancer risk'''
*** While the FDA retains a warning regarding the potential risk of prostate cancer in patients who are prescribed testosterone products (“patients treated with androgens may be at increased risk for prostate cancer”), there is accumulating evidence against a link between testosterone therapy and prostate cancer development.
** '''<span style="color:#ff0000">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.'''
*** There is no definitive evidence demonstrating that testosterone therapy is not safe for use in prostate cancer patients; the decision to commence testosterone therapy in men with a history of prostate cancer is a negotiated decision based on the perceived potential benefit of treatment.
*** '''Testosterone therapy can be considered in those men who have undergone radical prostatectomy with favorable pathology (e.g., negative margins, negative seminal vesicles, negative lymph nodes), and who have undetectable PSA postoperatively.'''
*** Post-radiation patients (with or without ADT exposure) placed on testosterone therapy do not experience recurrence of prostate cancer'''. A period of time should elapse after RT and before initiating testosterone''' '''therapy to allow adequate time to regain functional endogenous testosterone production'''.
*** '''PSA recurrence in men on testosterone therapy should be evaluated in the same fashion as untreated men. A discussion regarding the benefit of stopping testosterone therapy should include the possibility of a decline in PSA.'''
*** There are limited data in men on active surveillance who are candidates for testosterone therapy.