AndroGel Transfer to Women and Children: Severity Grading Rubric

Which product does this label cover?

The label is for Teva testosterone gel 1%, not for AndroGel. It states that dosage and administration for testosterone gel 1% differ from testosterone gel 1.62%, and that topical testosterone products may have different doses, strengths or application instructions that result in different systemic exposure [1].

Which signs does the label list in children?

The boxed warning opens with the finding itself: virilization has been reported in children who were secondarily exposed to testosterone gel, and children should avoid contact with unwashed or unclothed application sites in men using the product [1]. The warnings section then lists what was reported: enlargement of the penis or clitoris, development of pubic hair, increased erections and libido, aggressive behavior, and advanced bone age [1].

The label attributes some cases to use that departed from the recommended precautions, saying the risk of transfer was increased in some of these cases by not adhering to those precautions [1]. It names inappropriate changes in genital size, development of pubic hair, or libido in a child as the findings it ties to possible secondary exposure [1].

What does the label say about women and pregnancy?

Testosterone gel 1% is contraindicated in women who are pregnant, and the label states it can cause virilization of the female fetus [1]. It adds that pregnant women need to be aware of the potential for transfer of testosterone from men treated with the gel [1]. The pregnancy section describes testosterone as teratogenic, based on animal studies and its mechanism of action, and says exposure of a female fetus to androgens may result in varying degrees of virilization [1].

For adult women, the label lists changes in body hair distribution, a significant increase in acne, or other signs of virilization as findings it associates with possible secondary exposure [1].

What did a controlled transfer study find?

Rolf and colleagues, publishing in Clinical Endocrinology in 2002, ran two open randomized single-centre studies in healthy male volunteers using a 2.5% testosterone gel, a different concentration from the 1% product [2]. In the first, 12 men, about 60% of the testosterone applied to the skin could be recovered after 8 hours; when the skin had been washed with water, only about 14% could be recovered [2].

The second study involved 28 male volunteers whose own testosterone production was suppressed with 400 mg of norethisterone enanthate. After intense skin contact with a volunteer who had applied gel to his forearm, no increase in serum testosterone was found in the suppressed men [2]. The authors concluded that contamination of a second person, especially a female or prepubertal one, causing side effects seemed very unlikely [2].

That result is narrower than it can look. The gel was 2.5% rather than 1%, and the recipients were male volunteers rather than women or children [2].

What do case reports in children show?

A case series in Pediatrics in 2004 described children virilized by contact with adults using cutaneous steroid preparations; the parents were unaware of the danger of passive transfer, laboratory data were consistent with exogenous androgen exposure, and discontinuing contact produced a fall in androgen levels or regression of symptoms [3]. Case reports of this kind show that transfer has happened. They cannot say how often it happens.