Comparative studies involving newer testosterone formulations such as pellets or mucosal adhesive buccal tablets are limited . For example, a 1000 mg testosterone undeconoate preparation is marketed in Europe (Nebido®, Bayer, Berkshire, United Kingdom), while the closest equivalent in the United States is a 750 mg testosterone undeconate preparation (Aveed®, Endo International, Malvern, PA, United States) . There are multiple formulations and doses of injectable testosterone, with testosterone undeconoate having longer action than testosterone enanthate or cypionate . The University of Iowa Hospitals and Clinics (UIHC) are comprised of a 860-bed tertiary/quaternary care medical center with affiliated outpatient clinics at the central campus and at sites throughout the local geographic region. Intramuscular testosterone cypionate or enanthate have extended duration of action and are relatively inexpensive compared to other testosterone formulations , , . We were unable to ascertain any suspected cause from the available information in the medical record for 20 of the 48 patients. The remaining 6 patients were transgender men or non-binary individuals receiving gender-affirming hormones. Data was retrieved from the institutional electronic health record database and compared to pharmacy records. The suspected causes in the box on the bottom are derived from extensive chart review of the 48 patients. Gender identity is from the electronic health record field that can be voluntarily supplied by patient. For those prescribed topical gel, they should always be counseled about the proper anatomic site to apply the testosterone gel (in the shoulder and upper portion of the arm, carefully avoiding the phlebotomy site). It is worth noting that product insert material for testosterone gels may not mention the risk of contamination to phlebotomy. For those using testosterone topical gel, contamination of the venipuncture site by gel has previously been reported in a few case reports 20,21. A repeated total testosterone measurement was scheduled a week later, and it also came back elevated with a concentration of 1291 ng/dL (44.8 nmol/L). The primary care physician called the patient to discuss this result, and the patient indicated he had applied testosterone gel earlier in the morning to the same arm in which he received venipuncture for the testosterone concentration. A repeated measurement 2 weeks later was 19 ng/dL (0.7 nmol/L); however, the patient admitted being inconsistent with testosterone gel application. Most testosterone serum measurements (39,878 of 40,979, 97.3 %) were performed in patients seen in the outpatient setting. The majority of testosterone serum measurements were for patients not prescribed any testosterone-containing medications at the time of the blood draw (Table 1; Fig. 1). We utilized EHR reporting tools (Epic Reporting Workbench) to retrieve all serum testosterone measurements from May 1, 2009 to March 31, 2022 along with pharmacy medical records for any testosterone preparations prescribed to patients who had serum testosterone measurements. Certainly, those that may be using or even abusing testosterone may wish to be informed of potential serious adverse effects. Thus, in this instance the concentrations used in vitro are not reflective of what is seen in vivo in humans. While it can certainly be argued that the relationship between testosterone and SHBG is dynamic and can be altered in cases of exogenous administration (amongst other variables), ultimately what matters most is the available concentration in brain tissue (see Section 2.2). In fact, it is nearly 3 times greater than the upper limit of normal for total blood testosterone levels in eugonadal males 12,13,14. First, it should be noted that contrary to the claims of some authors , 100 nmol is not within any accepted physiological range for eugonadal males. While the adverse effects of testosterone—and in a broader sense, all anabolic-androgenic steroids—are fairly well described, more recent attention has been devoted to potential neurological side effects 18,19. More research is needed as the currently available data are limited; however, what is available provides rather weak evidence to suggest that testosterone use or abuse has neurotoxic potential in humans.
