There are a variety of testosterone gels, each with different application methods. TRT gel involves rubbing testosterone onto your skin, often the upper arms or shoulder, and waiting for it to be absorbed.4 This method helps you return your testosterone back to healthy levels.5 Women should remain within the female physiologic testosterone range when therapy is used, not chase male-style replacement levels.
In most cases, the concentrations studied in vitro are unlikely to be reached in the human brain. It has been increasingly speculated that aside from more well-established side effects, testosterone may cause neurological damage. Due to declining testosterone levels from a variety of causes, testosterone replacement therapy (TRT) is increasingly utilized, while testosterone is also abused for aesthetic and performance-enhancing purposes. The risk of secondary exposure can be limited by hand-washing immediately after application of the gel, covering of the area with clothing, and limiting direct contact of skin with family members. This change in dose led to inadequate therapy, with a later increase in dose by another healthcare provider. Endocrinology documented that this very high value was likely a result of either gel contamination or a laboratory error. Approximately 3 months later, the patient reported being pleased with the masculinizing effects including growth of facial hair, deepening of the voice, and enlargement of the clitoris.
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.
Testosterone as GAHT uses the same testosterone formulations and modalities as for male hypogonadism, although costs and insurance coverage for some formulations are limiting factors for some patients in the United States . Testosterone therapy is also used as gender-affirming hormone therapy (GAHT) in transgender and non-binary patients who desire masculinization, typically in those individuals whose sex assigned at birth is female 13,14. In recent years, topical formulations (gels, transdermal patches) have been increasingly popular, influenced by factors such as patient preference, consumer marketing, and availability of insurance coverage 2,5,, , . Testosterone as replacement therapy for male hypogonadism or as gender-affirming hormone therapy for transgender and non-binary patients has increased worldwide. We hypothesized that measuring estradiol (E) and calculating the T/E ratio could give a biochemical clue for contamination because skin-originating testosterone will not be aromatized to estradiol.
For men, the goal is usually to bring testosterone into the normal range for healthy men and match that to clinical response. It should also be noted that even in this study, though often cited as evidence that AASs are capable of reaching micromolar concentrations in the human brain , mean concentrations were actually 233 nmol, with a maximum range of 898 nmol in the CSF, which itself can only be considered a potential surrogate of brain concentrations 58,65. It is also important to note that even in cases where a given concentration has been shown to have toxic effects in a given cell line (i.e., ≥100 nmol), maintaining blood concentrations of this magnitude would also be necessary, as short-term exposure (e.g., 24 h) in vitro has not been shown to be capable of producing cellular damage .
Men and women have different physiologic ranges, different evidence bases for treatment, and different monitoring goals. Supraphysiologic levels may increase adverse effects without improving the intended therapeutic outcome. Monitoring should also focus on clinical response and signs of androgen excess (Parish et al., Climacteric, 2021).