AndroGel Transfer to Women and Children: The Biology of Why It Happens

What does secondary exposure mean?

Secondary exposure means a person who did not apply the gel is exposed to testosterone from the treated person's skin. The boxed warning on the testosterone gel 1% label says virilization has been reported in children who were secondarily exposed to testosterone gel, and that children should avoid contact with unwashed or unclothed application sites in men using the gel [1].

That label is Teva's testosterone gel 1%, not AndroGel's. It says its dosage and administration differ from testosterone gel 1.62%, and that topical testosterone products may have different strengths or application instructions that result in different systemic exposure [1].

Why does the gel transfer at all?

A topical testosterone gel is applied to the skin so that testosterone is absorbed through it. In a study of a 2.5% testosterone gel in 12 healthy men, about 60% of the applied testosterone could still be recovered from the skin 8 hours after application; when the skin had been washed with water, only about 14% was recovered [3]. In the same report, intense skin contact with the forearm of a volunteer who had applied the gel did not raise serum testosterone in 28 men whose own production had been suppressed, and the authors considered contamination of a second person, especially a female or prepubertal one, very unlikely for that gel [3].

The 1% label describes transfers that did occur: cases of secondary exposure resulting in virilization of children were reported in postmarketing surveillance, and children and women should avoid contact with unwashed or unclothed application sites [1]. A report in Pediatrics described children virilized by contact with adults using topical androgen preparations; parents were unaware of the dangers of passive transfer, laboratory data were consistent with exogenous androgen exposure, and stopping contact led to lower androgen levels or regression of symptoms [2].

What happens when a child is exposed?

The label lists the signs reported with secondary exposure in children: enlargement of the penis or clitoris, development of pubic hair, increased erections and libido, aggressive behavior, and advanced bone age [1]. It says that in most cases these signs and symptoms regressed with removal of the exposure to testosterone gel. In a few cases, enlarged genitalia did not fully return to age-appropriate normal size, and bone age remained modestly greater than chronological age [1]. The label also says the risk of transfer was increased in some cases by not adhering to precautions for appropriate use of the topical testosterone product [1].

What about women and pregnancy?

The label says women should avoid contact with unwashed or unclothed application sites [1]. In adult women, it lists changes in body hair distribution, a significant increase in acne, or other signs of virilization as possible signs of secondary exposure [1]. Testosterone gel 1% is contraindicated in women who are pregnant. The label says testosterone gel 1% can cause virilization of the female fetus when administered to a pregnant woman, and that pregnant women need to be aware of the potential for transfer of testosterone from men treated with the gel [1].