In this instance, it is known that blood concentrations of testosterone overestimate the levels found in the human brain by 3–10 fold 51,52,53,54. While doses of exogenous testosterone normally utilized for TRT purposes are unlikely to elevate plasma testosterone to concentrations that have been shown to have neurotoxic potential in vitro, it is even more unlikely once tissue distribution is considered. Just as with pharmacological targets, utilizing extreme concentrations may not accurately reflect the actual risk of cell/tissue damage 49,50. These concentrations have not been reached in studies utilizing supraphysiological doses of exogenous testosterone (see Table 1). Other authors have indicated that concentrations of 100–500 µmol are typically reached with a supraphysiological dose of 600 mg of testosterone enanthate weekly , which is also incorrect (see Table 1). Comparison of in vivo testosterone plasma concentrations with neurotoxic in vitro concentrations. Furthermore, even amongst those that are abusing testosterone, consistent concentrations of this magnitude in plasma are not expected, except for those using quantities of 500–600 mg or more of [buy testosterone online no prescription](https://git.lenfortech.com/tangelatooth1) cypionate/enanthate weekly (see Table 1) 30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46. This same group’s work was used in lay press articles to claim that even levels of testosterone seen with TRT can "lead to a catastrophic loss of brain cells" . The typical replacement doses utilized for TRT would not be expected to reach this concentration on average (see Table 1) 29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46. Several groups have investigated the potential neurotoxicity of testosterone in vitro by utilizing human and rodent cell lines 25,26,27,28. Testosterone levels may generally decline with advancing age and may eventually reach a point of "testosterone deficiency," although there are other causes of low testosterone, including certain injuries, medications, obesity, illnesses, radiation exposure, and genetic conditions 13,14,15,16,17. Observational data in humans concerning the potential for deleterious changes in brain structure and [music.batalp.com](https://music.batalp.com/elizbethcarnar) function are limited by their inherent design as well as significant potential confounders. FDA now requires stronger warnings on the product labels about the risk of accidental exposure. In most cases, the adverse effects went away when the child was no longer exposed to the drug. Clinical guidelines for management of male hypogonadism and treatment of gender dysphoria often recommend periodic monitoring of serum testosterone (e.g., 1 month after starting therapy, then 3–6 months, and then annually) 11,13. In those with prostate glands, high testosterone concentrations can worsen benign prostatic hyperplasia and theoretically accelerate growth of pre-existing prostate cancer (if present) . Regardless of clinical indication, excessively high doses of testosterone have risk of adverse effects, including acne, polycythemia, hypertension, dyslipidemia, and elevated cardiovascular risk 6,7,16,17. The high testosterone concentrations prompted further work-up, including retesting and endocrinology consultation. Commonly used formulations of testosterone include intramuscular, transdermal patch, and topical gel, each of which has differing pharmacokinetics and practical challenges. Clinicians and laboratory specialists should stay attentive to this common form of contamination and instruct patients accordingly. If your partner is rubbing testosterone gel in for you, make sure they use gloves. 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 buy online](https://www.singuratate.ro/@carlosfishbour) 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. Oral administration of testosterone is limited by low bioavailability due to poor gastrointestinal absorption and extensive first pass metabolism , , , . These included 5 males with primary hypogonadism, 1 male with panhypopituitarism, and a non-binary patient with gender dysphoria. The present study involves a retrospective search over a 13-year period across all clinical sites at an academic medical center. However, artifactually high serum testosterone concentrations in patients receiving topical testosterone gels can occur if the venipuncture site is contaminated by gel during the phlebotomy procedure. Health care providers should be aware of the possibility of topical gel contamination to avoid unnecessary downstream consequences of apparent supraphysiologic serum testosterone concentrations. On the other hand, patients prescribed topical testosterone therapy achieved lower serum testosterone concentrations at the beginning of treatment, but significant serum testosterone fluctuations were more likely to be observed. We performed chart review of the 65 patients identified in the EHR database as being prescribed topical gel testosterone in conjunction with a testosterone serum concentration of 1000 ng/dL or higher. This phenomenon was first reported in 2010 as a case report of two instances of spuriously elevated serum testosterone concentrations in a patient resulting from contamination of the antecubital fossa by testosterone gel prior to phlebotomy . Gel contamination should be considered as a possible cause of otherwise unexplained high testosterone serum concentration in patients receiving topical testosterone gel formulations. Out of 578 unique patients using testosterone topical gel, a total of 48 patients had at least 1 testosterone serum concentration exceed 1000 ng/dL. A popular form of TRT is transdermal gel, with the benefit of a topical, less invasive method of application.2 However, a common concern for patients is the risk of secondary transfer. Thus, the utilization of high concentrations of free testosterone in vitro results in an untenable comparison with total plasma testosterone concentrations reached even after supraphysiological doses of exogenous [testosterone for sale](https://recrutement.fanavenue.com/companies/medical-calculators,-dosage-calculations,-clinical-calculators-globalrph/). It should also be noted that these concentrations discussed relate to total testosterone (i.e., testosterone that is unbound and bound by sex hormone binding globulin (SHBG) and albumin), while "free testosterone" or testosterone that is not bound to SHBG and albumin constitutes only 2–4% of total circulating testosterone; 50–60% of total testosterone is bound by SHBG and is generally not considered available to tissues such as the brain 13,14,16,17. There were additional cases of high testosterone serum concentration that may have been falsely elevated due to gel contamination but without sufficient supporting evidence available in the health record. Authors of these studies have proposed that concentrations as low as 100 nmol of [buy testosterone cypionate](https://git.lucas-michel.fr/alisons2699178) may be neurotoxic, while also indicating that this concentration is consistent with the "high normal range" of total blood testosterone in men, and acknowledging that concentrations of 1 µmol or greater are in the supraphysiological range . The present study does not have data on fasting status of patients who had serum testosterone measurements performed or on the exact timing of last testosterone dose to time of venipuncture. For those prescribing testosterone gels, patient counseling and provider awareness of this potential cause of spuriously high testosterone serum concentrations is important. Three subsequent total serum testosterone concentrations have been between 244 ng/dL (8.5 nmol/L) and 644 ng/dL (22.3 nmol/L). At the time the high serum [buy testosterone online](https://revenu.live/@meganfarris000?page=about) concentrations were measured, the average age of patients was 40.3 years with a standard deviation (SD) of ± 17.1 years. Formulations of testosterone other than intramuscular, topical gel, or transdermal patch were uncommon, with only 88 testosterone serum measurements (32 unique patients) in patients prescribed alternate formulations such as mucoadhesive buccal tablets or subcutaneous pellets. Some serum testosterone measurements (especially those ordered for children or female patients who generally have lower serum testosterone concentrations) were sent to ARUP Laboratories (Salt Lake City, UT) which analyzed by liquid chromatography/tandem mass spectrometry (LC/MS/MS).
In this instance, it is known that blood concentrations of testosterone overestimate the levels found in the human brain by 3–10 fold 51,52,53,54. While doses of exogenous testosterone normally utilized for TRT purposes are unlikely to elevate plasma testosterone to concentrations that have been shown to have neurotoxic potential in vitro, it is even more unlikely once tissue distribution is considered. Just as with pharmacological targets, utilizing extreme concentrations may not accurately reflect the actual risk of cell/tissue damage 49,50. These concentrations have not been reached in studies utilizing supraphysiological doses of exogenous testosterone (see Table 1). Other authors have indicated that concentrations of 100–500 µmol are typically reached with a supraphysiological dose of 600 mg of testosterone enanthate weekly , which is also incorrect (see Table 1). Comparison of in vivo testosterone plasma concentrations with neurotoxic in vitro concentrations. Furthermore, even amongst those that are abusing testosterone, consistent concentrations of this magnitude in plasma are not expected, except for those using quantities of 500–600 mg or more of [buy testosterone online no prescription](https://git.lenfortech.com/tangelatooth1) cypionate/enanthate weekly (see Table 1) 30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46. This same group’s work was used in lay press articles to claim that even levels of testosterone seen with TRT can "lead to a catastrophic loss of brain cells" . The typical replacement doses utilized for TRT would not be expected to reach this concentration on average (see Table 1) 29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46. Several groups have investigated the potential neurotoxicity of testosterone in vitro by utilizing human and rodent cell lines 25,26,27,28. Testosterone levels may generally decline with advancing age and may eventually reach a point of "testosterone deficiency," although there are other causes of low testosterone, including certain injuries, medications, obesity, illnesses, radiation exposure, and genetic conditions 13,14,15,16,17. Observational data in humans concerning the potential for deleterious changes in brain structure and [music.batalp.com](https://music.batalp.com/elizbethcarnar) function are limited by their inherent design as well as significant potential confounders. FDA now requires stronger warnings on the product labels about the risk of accidental exposure. In most cases, the adverse effects went away when the child was no longer exposed to the drug. Clinical guidelines for management of male hypogonadism and treatment of gender dysphoria often recommend periodic monitoring of serum testosterone (e.g., 1 month after starting therapy, then 3–6 months, and then annually) 11,13. In those with prostate glands, high testosterone concentrations can worsen benign prostatic hyperplasia and theoretically accelerate growth of pre-existing prostate cancer (if present) . Regardless of clinical indication, excessively high doses of testosterone have risk of adverse effects, including acne, polycythemia, hypertension, dyslipidemia, and elevated cardiovascular risk 6,7,16,17. The high testosterone concentrations prompted further work-up, including retesting and endocrinology consultation. Commonly used formulations of testosterone include intramuscular, transdermal patch, and topical gel, each of which has differing pharmacokinetics and practical challenges. Clinicians and laboratory specialists should stay attentive to this common form of contamination and instruct patients accordingly. If your partner is rubbing testosterone gel in for you, make sure they use gloves. 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 buy online](https://www.singuratate.ro/@carlosfishbour) 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. Oral administration of testosterone is limited by low bioavailability due to poor gastrointestinal absorption and extensive first pass metabolism , , , . These included 5 males with primary hypogonadism, 1 male with panhypopituitarism, and a non-binary patient with gender dysphoria. The present study involves a retrospective search over a 13-year period across all clinical sites at an academic medical center. However, artifactually high serum testosterone concentrations in patients receiving topical testosterone gels can occur if the venipuncture site is contaminated by gel during the phlebotomy procedure. Health care providers should be aware of the possibility of topical gel contamination to avoid unnecessary downstream consequences of apparent supraphysiologic serum testosterone concentrations. On the other hand, patients prescribed topical testosterone therapy achieved lower serum testosterone concentrations at the beginning of treatment, but significant serum testosterone fluctuations were more likely to be observed. We performed chart review of the 65 patients identified in the EHR database as being prescribed topical gel testosterone in conjunction with a testosterone serum concentration of 1000 ng/dL or higher. This phenomenon was first reported in 2010 as a case report of two instances of spuriously elevated serum testosterone concentrations in a patient resulting from contamination of the antecubital fossa by testosterone gel prior to phlebotomy . Gel contamination should be considered as a possible cause of otherwise unexplained high testosterone serum concentration in patients receiving topical testosterone gel formulations. Out of 578 unique patients using testosterone topical gel, a total of 48 patients had at least 1 testosterone serum concentration exceed 1000 ng/dL. A popular form of TRT is transdermal gel, with the benefit of a topical, less invasive method of application.2 However, a common concern for patients is the risk of secondary transfer. Thus, the utilization of high concentrations of free testosterone in vitro results in an untenable comparison with total plasma testosterone concentrations reached even after supraphysiological doses of exogenous [testosterone for sale](https://recrutement.fanavenue.com/companies/medical-calculators,-dosage-calculations,-clinical-calculators-globalrph/). It should also be noted that these concentrations discussed relate to total testosterone (i.e., testosterone that is unbound and bound by sex hormone binding globulin (SHBG) and albumin), while "free testosterone" or testosterone that is not bound to SHBG and albumin constitutes only 2–4% of total circulating testosterone; 50–60% of total testosterone is bound by SHBG and is generally not considered available to tissues such as the brain 13,14,16,17. There were additional cases of high testosterone serum concentration that may have been falsely elevated due to gel contamination but without sufficient supporting evidence available in the health record. Authors of these studies have proposed that concentrations as low as 100 nmol of [buy testosterone cypionate](https://git.lucas-michel.fr/alisons2699178) may be neurotoxic, while also indicating that this concentration is consistent with the "high normal range" of total blood testosterone in men, and acknowledging that concentrations of 1 µmol or greater are in the supraphysiological range . The present study does not have data on fasting status of patients who had serum testosterone measurements performed or on the exact timing of last testosterone dose to time of venipuncture. For those prescribing testosterone gels, patient counseling and provider awareness of this potential cause of spuriously high testosterone serum concentrations is important. Three subsequent total serum testosterone concentrations have been between 244 ng/dL (8.5 nmol/L) and 644 ng/dL (22.3 nmol/L). At the time the high serum [buy testosterone online](https://revenu.live/@meganfarris000?page=about) concentrations were measured, the average age of patients was 40.3 years with a standard deviation (SD) of ± 17.1 years. Formulations of testosterone other than intramuscular, topical gel, or transdermal patch were uncommon, with only 88 testosterone serum measurements (32 unique patients) in patients prescribed alternate formulations such as mucoadhesive buccal tablets or subcutaneous pellets. Some serum testosterone measurements (especially those ordered for children or female patients who generally have lower serum testosterone concentrations) were sent to ARUP Laboratories (Salt Lake City, UT) which analyzed by liquid chromatography/tandem mass spectrometry (LC/MS/MS).