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. Given the clinical and commercial testosterone landscape, the American Urological Association (AUA) identified a need to produce an evidence-based document that informs clinicians on the proper assessment and management of patients with testosterone deficiency. Only a few side effects like gynecomastia and temporary mastalgia were reported in patients with excessive endogenous T and estradiol levels (33). Interestingly, hCG treatment decreases circulating FSH levels (7, 10, 11), which are typically elevated in most NOA patients. However, patient No. 4 exhibited elevated estradiol levels during treatment and required the addition of an aromatase inhibitor to keep the testosterone to estradiol ratio within optimal levels. Specifically, baseline endogenous FSH and LH levels were markedly elevated, and azoospermia was found in repeated semen analyses even though the patient had stopped using steroids for several years (Table-1). 1-89, 10These results are consistent with other meta-analyses,296 yet methodological flaws in the study design may underestimate the true rate and magnitude of improvement in erectile function. As such, low testosterone is likely better considered as a covariate with these comorbid conditions rather than as an independent observation. Specifically, the AUA does not recommend routine PSA testing in men years of age unless they are at higher risk (e.g., positive family history, African American race), at which point decisions regarding PSA testing should be individualized. Finally, a randomized trial of 76 men (mean age 50.6 years), who had at least 1 ejaculatory dysfunction symptom and at least 2 testosterone tests 182 In the event that a patient may have hypogonadotropic hypogonadism, adjunctive tests should be ordered. However, the literature at this time fails to define the LH level below which such adjunctive testing is warranted. Similarly, in the event patients have unexplained anemia that improves on testosterone therapy, continuation can be considered even in the absence of other symptom improvement. Two RCTs compared treatment of testosterone deficient males with SERMs versus testosterone versus placebo and found that sperm concentration was maintained (comparable to placebo) for males treated with the SERMs, but was significantly decreased for males on exogenous testosterone.401, 402 Finally, Helo et al. conducted a prospective, double-blind, RCT comparing the SERM clomiphene citrate versus the AI anastrozole in infertile males with testosterone deficiency. One study of 60 patients undergoing long-term therapy of 50 mg methyltestosterone three times a day found that nearly one-third of patients, none of whom had a history of liver disease, returned abnormal liver function tests and/or liver scans.387 Testosterone undecanoate is an oral testosterone analogue that is absorbed via the intestinal lymphatics allowing it to avoid the first pass liver effect. The researchers administered hCG to each of the men for around 8 months. In females, the ovaries make testosterone in comparatively small amounts. In males, the testicles are the primary source of testosterone. A doctor or a nurse taught patients how to set the dose and administer the medication. All patients had a normal karyotype, no Y chromosome microdeletions, or cystic fibrosis pathogenic variants. Another patient had a history of anejaculation due to spinal cord injury, and again, an atypical presentation as azoospermia was noticed on examination of specimens obtained by electroejaculation. Most patients had an unremarkable history explaining NOA, although one patient reported cryptorchidism. In all patients, NOA was confirmed by testicular histopathology of specimens taken by TESA. Patients were informed that recombinant gonadotropin therapy for their condition was off-label and that evidence concerning its effectiveness and safety was minimal. Gynecomastia is a benign enlargement of the male breast tissue that can occur at times of male androgen/estrogen change (alteration in testosterone/estradiol E2 ratio), infancy, adolescence, or old age, and may be a sign of low serum testosterone. The scientific literature examining the relationship between ED and low testosterone is further limited by the variability in, or absence of, the definition of ED, incomplete vascular comorbidity information, as well as variability in the thresholds used to define low testosterone. Studies whose primary endpoint was to measure the association between depression and low testosterone found that men with low testosterone have a significantly higher incidence of depression as well as a shorter time to onset of depression. Findings are similar to the previously cited pharmacokinetic study (750 mg in 3 mL) in which one patient in 130 (438 It is notable that similar findings have also been observed with other oil-based testosterone preparations that are currently most often self-administered at home (typically with lower volumes of injection).445 For trough total testosterone values 300 ng/dL are achieved at the end of an injection period. In contrast to topical agents where a percentage of men have difficulty achieving therapeutic levels within standard dosing ranges, injectable testosterone preparations are able to achieve therapeutic levels in almost any clinical scenario. 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.
