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.
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.
Future studies can aim to replicate this finding with controlled application of various formulations of testosterone topical gel to sites used for phlebotomy. Our retrospective review at an academic medical center revealed at least 7 cases over a 13-year period where this phenomenon was suspected to have resulted in a serum testosterone concentration of 1000 ng/dL or higher. Discussion with the patient indicated application of the testosterone gel to the arm shortly before phlebotomy for the testosterone measurement. Following this measurement, the provider called the patient and learned that the patient had applied the topical gel near the site of phlebotomy approximately 45 min before the blood draw and suspected something similar had happened with the previous elevated measurement. A 46-year-old male with an 11-year history of primary hypogonadism and erectile dysfunction was prescribed 50 mg of topical testosterone gel/day. In investigating the case, the endocrinologist found the patient had used his testosterone gel on a large surface area of his bicep the morning his venipuncture was performed. The patient had been clinically stable, without any symptoms or signs referable to high sex-hormone concentrations.
In general, guidelines aim for symptom improvement within the normal physiologic male range rather than supraphysiologic levels (Bhasin et al., Journal of Clinical Endocrinology & Metabolism, 2018). In transdermal therapy, timing matters differently. One reason lab conversations around TRT become confusing is that testosterone values are not independent of timing. This means women's TRT targets should not be "as high as possible while feeling good." The better standard is "the lowest effective exposure that stays within the female physiologic range and supports the specific symptom target under monitoring." Testosterone therapy in women has a much narrower evidence-based indication, with the strongest support in postmenopausal women with hypoactive sexual desire disorder (Davis et al., Journal of Sexual Medicine, 2019; Parish et al., Climacteric, 2021). Major consensus statements emphasize that there is no blood testosterone cutoff that can diagnose a female androgen-deficiency syndrome the way clinicians diagnose male hypogonadism.
Concentrations well beyond 100 nmol, and especially into the 1 µmol to 100 µmol range, for total testosterone are highly unlikely, even in those abusing testosterone for athletic/aesthetic purposes. While pharmacokinetic data gathered in humans administered varying doses of testosterone esters either intramuscularly or subcutaneously vary considerably depending upon the route of administration and sampling method, these data generally show that only quantities used as part of testosterone abuse are capable of reaching concentrations of 100 nmol or greater on a consistent basis. In healthy eugonadal men, testosterone is produced primarily by the Leydig cells of the testicles and results in the total daily production of approximately 6–7 mg/day, although a range of 3–10 mg total testosterone production is often cited as well 1,2,3,4,5,6,7,8,9,10.
In men, they’ve been linked to low testosterone, reduced sperm motility, and lower sperm count. Some of these chemicals mimic natural hormones like estrogen, while others disrupt metabolic pathways to suppress the production of testosterone. Recognising the signs of low testosterone is therefore important for timely intervention.
Testosterone transfer occurs because not all of the testosterone applied to the skin is absorbed and metabolised straight away, meaning a residue of the hormone remains on the surface of the skin.7,8 For children, testosterone exposure can cause the development of pubic hair, increased libido and enlargement of sex organs, and aggression.7 Transdermal gels are a popular form of TRT because they are easy to use and painless. In this article, we’ll explore whether secondary transfer risk is a valid concern and some practical steps you can take to reduce your risk. Such content is not intended to replace an evaluation with a qualified healthcare professional of your choosing and is not intended as medical advice. • Lab timing, assay quality, symptoms, and side effects all matter.
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.

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