Testosterone replacement therapy, most commonly available as a transdermal gel, is increasingly used to treat men with testosterone deficiency.

Although gels provide a convenient, noninvasive alternative to injections, hormones residues can remain on the skin after application and be transferred through direct contact, posing a risk to close contacts.

A case report described a girl who developed unusually large genitals after secondary exposure to testosterone gel through close skin-to-skin contact with her father.

Treatment Profile

Transdermal testosterone bypasses the first-pass effect and is painless compared with intramuscular injections. Both patches and gels are available for use.

Patches frequently cause dermatitis, leading to approximately 10% of users discontinuing treatment.

Gels typically contain 1% or 2% testosterone, purified water, ethanol, and polyacrylate, with the latter serving as the gel matrix.

Ethanol acts as both vehicle and solvent in transdermal gels to enhance skin absorption.
Manufacturers recommend applying the gel to the abdomen, shoulders, upper arms, or inner thighs.

Patients should wash their hands immediately after application and cover the treated area with clothing. Unlike intramuscular therapy, dermal transfer to others is possible, although published reports on this are uncommon.

Transfer Risk

The recommended daily dose of testosterone gel is 50-60 mg. The endogenous production in men averages 5-10 mg daily. The systemic bioavailability of transdermal formulations is approximately 10%-15%.

A 2002 pharmacokinetic study found that up to 60% of the applied gel could still be detected in the skin 8 hours after use.

The amount detected did not change between 10 minutes and 8 hours, indicating that absorption into the stratum corneum occurs within minutes. 

Washing the application site reduced the residual gel content from 60% to 15%.
Researchers have evaluated close skin contact between users and other individuals. No significant increase in serum testosterone levels was observed in the contacts. 

The study found that absorption depends on alcohol evaporation. As ethanol is no longer detectable on the skin after approximately 10 minutes, transfer beyond that point is unlikely.

Clinical Case

Despite the low observed risk, several cases of secondary exposure have been reported.

In one case, virilization, including penile enlargement and growth of pubic hair and facial acne, developed in a 2-year-old boy over a period of months.

This sexual development was induced by incidental and unintentional dermal exposure to testosterone cream applied to his father’s arms and back.

Laboratory findings showed a testosterone concentration of 3.3 nmol/L (normal concentration < 0.6 nmol/L), with suppressed luteinizing hormone (0.1 IU/L; normal concentration < 0.2 IU/L), and follicle-stimulating hormone (0.2 IU/L; normal concentration < 0.5 IU/L).

Although the child’s father had been informed about the risk for transfer to his partner, he did not apply the same precautions as his children and sometimes played shirtless with them shortly after application.

Except for penile size, the other signs of virilization diminished several months after the exposure was discontinued.

Risk Reduction

Although case reports raise concerns, they remain rare compared to prescriptions. In the UK, 50,000-100,000 people use testosterone, mostly in the form of gel. If secondary transfer were common, far more exposures among close contacts would have been reported.

Patients should receive detailed and clear instructions before starting treatment, and clinicians should emphasize that responsible use is essential to protect close contacts.

This story was translated from Univadis Germany.