Chassidy Galarza
IscrittiDi
In the retrospective timeframe, there was a total of 19,623 unique patients with 40,979 total serum testosterone measurements. Testosterone topical gels generally show less variability in serum concentrations compared to transdermal patch . Testosterone concentrations in patients receiving intramuscular testosterone ester injections are influenced by timing of blood sample relative to last injection, with peak concentrations between 2 and 4 days after injection and a total duration of action of approximately 2 weeks. However, there is debate on the requirement for a fasting specimen, as some studies have not shown a significant impact of fasting status on serum testosterone concentrations . When monitoring testosterone therapy, it is important to recognize that a variety of factors (e.g., age, genetic polymorphisms, drug-drug interactions, medication adherence or misuse, contamination of sample, fasting status) can influence measured serum testosterone concentration. Overall, we present 7 cases of spuriously high testosterone concentrations strongly suspected to be due to venipuncture performed near or at the location of prior testosterone gel application.
That is why Humanaut Health's Hormones program fits best when patients want careful interpretation instead of generic target ranges. The AUA guideline is often cited because it uses a total testosterone below 300 ng/dL as a reasonable diagnostic cutoff for testosterone deficiency. For women, testosterone therapy has a much narrower evidence-based use case, and treatment should remain within the female physiologic range rather than approach male-style replacement targets (Mulhall et al., Journal of Urology, 2018; Davis et al., Journal of Sexual Medicine, 2019). For men, replacement therapy is meant to restore testosterone into a normal physiologic range in the setting of confirmed deficiency. There is no universal magic number that is ideal for every patient on testosterone therapy. In vitro data utilizing concentrations that are irrelevant to in vivo administration should not be relied upon as supportive evidence of neurological damage. While testosterone use for TRT is still subject to some controversy, the available data are rather weak to suggest that neurological damage or an increased risk of neurodegenerative disease is a risk with long-term use either at therapeutic doses or those generally used for athletic/aesthetic purposes.
Unfortunately, the Food and Drug Administration (FDA) has received reports about these products causing adverse effects in children. Adverse effects can occur in children and women who are accidentally exposed to the drug. However, some products may vary, so it is important to talk to your pharmacist and read that package insert for how and where to apply the gel. It is important in maintaining bone health, energy levels, mood, and sexual desire. This section collects any data citations, data availability statements, or supplementary materials included in this article. Lastly, the current study was performed in the United States, and there are differences in the formulation and available doses of marketed testosterone prescriptions in other countries. Location of application will influence risk of contaminating venipuncture sites , , .
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 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.
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 testosterone cypionate/enanthate weekly (see Table 1) 30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46.
There are also published cases where clinically significant elevations in testosterone concentration resulted from secondary transfer of testosterone gel from one person to another, including children 21,23,24, although controlled studies show this is likely a rare phenomenon . A publication in 2013 reported the same phenomenon in two adult patients prescribed testosterone gel for hypogonadism . Therefore, sampling time and age are important factors to consider when monitoring and interpreting serum testosterone in patients on TRT or GAHT. The influence of circadian rhythms on exogenous testosterone is unknown, but timing of dose and testosterone formulation influence measured testosterone serum concentrations. In the United States, testosterone formulations approved by the Food and Drug Administration (FDA) for testosterone replacement therapy (TRT) include intramuscular injections, transdermal patches, topical gels, implantable subcutaneous pellets, and buccal tablets , , .
That is why Humanaut Health's Hormones program fits best when patients want careful interpretation instead of generic target ranges. The AUA guideline is often cited because it uses a total testosterone below 300 ng/dL as a reasonable diagnostic cutoff for testosterone deficiency. For women, testosterone therapy has a much narrower evidence-based use case, and treatment should remain within the female physiologic range rather than approach male-style replacement targets (Mulhall et al., Journal of Urology, 2018; Davis et al., Journal of Sexual Medicine, 2019). For men, replacement therapy is meant to restore testosterone into a normal physiologic range in the setting of confirmed deficiency. There is no universal magic number that is ideal for every patient on testosterone therapy. In vitro data utilizing concentrations that are irrelevant to in vivo administration should not be relied upon as supportive evidence of neurological damage. While testosterone use for TRT is still subject to some controversy, the available data are rather weak to suggest that neurological damage or an increased risk of neurodegenerative disease is a risk with long-term use either at therapeutic doses or those generally used for athletic/aesthetic purposes.
Unfortunately, the Food and Drug Administration (FDA) has received reports about these products causing adverse effects in children. Adverse effects can occur in children and women who are accidentally exposed to the drug. However, some products may vary, so it is important to talk to your pharmacist and read that package insert for how and where to apply the gel. It is important in maintaining bone health, energy levels, mood, and sexual desire. This section collects any data citations, data availability statements, or supplementary materials included in this article. Lastly, the current study was performed in the United States, and there are differences in the formulation and available doses of marketed testosterone prescriptions in other countries. Location of application will influence risk of contaminating venipuncture sites , , .
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 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.
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 testosterone cypionate/enanthate weekly (see Table 1) 30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46.
There are also published cases where clinically significant elevations in testosterone concentration resulted from secondary transfer of testosterone gel from one person to another, including children 21,23,24, although controlled studies show this is likely a rare phenomenon . A publication in 2013 reported the same phenomenon in two adult patients prescribed testosterone gel for hypogonadism . Therefore, sampling time and age are important factors to consider when monitoring and interpreting serum testosterone in patients on TRT or GAHT. The influence of circadian rhythms on exogenous testosterone is unknown, but timing of dose and testosterone formulation influence measured testosterone serum concentrations. In the United States, testosterone formulations approved by the Food and Drug Administration (FDA) for testosterone replacement therapy (TRT) include intramuscular injections, transdermal patches, topical gels, implantable subcutaneous pellets, and buccal tablets , , .
