Serum testosterone levels in non-dosed females after secondary exposure to 1.62% testosterone gel: effects of clothing barrier on testosterone absorption

Objective: To evaluate secondary exposure of testosterone transferred to females from a male partner, dosed with 1.62% testosterone gel after direct skin-to-skin contact with the application site, and to investigate the effect of wearing a t-shirt on testosterone transfer. Research design and methods: Across three studies, a total of 72 healthy males applied 5.0 g 1.62% testosterone gel to their abdomen alone, upper arms/shoulders alone, or a combination of their upper arms/shoulders and abdomen (single dose or once daily for 7 days). Male-female contact occurred 2 or 12 hours after testosterone gel application, with males either wearing or not wearing a t-shirt. There were 15 minutes of supervised contact with the application site between the male and his female partner. Blood samples were collected over a 24 hour period in females for assessment of serum testosterone levels at baseline and after contact. Main outcome measures: Pharmacokinetic parameters included C-max (maximum serum concentration), AUC(0-24) (area under the serum concentration-time curve from 0-24 hours), and C-av (time-averaged concentration over the 24-hour period post-contact). Subjects were monitored for adverse events. Clinical trial registration NCT numbers: Study 1 was not registered (first subject enrolled 8 March 2007); Study 2: 00998933; Study 3, 01130298. Results: Testosterone levels (C-av and C-max) in females increased 86-185% from baseline after direct abdominal skin contact, although C-av levels remained within female eugonadal range. Testosterone concentrations returned to baseline within 48 hours after last skin contact. A t-shirt barrier reduced testosterone transfer by approximately 40-48% when 5.0 g of testosterone gel was applied to the abdomen alone. A t-shirt barrier prevented transfer when 5.0 g of testosterone gel was applied to the upper arms and shoulders or to a combination of the upper arms and shoulders and the abdomen (C-max and C-av increased by approximately 5-11%). No major safety events were observed during the studies. Conclusions: There is a risk of testosterone transfer from males using 1.62% testosterone gel to others who come in contact with the application site for at least 12 hours after application. Secondary exposure can be mitigated by means of a t-shirt barrier. Study limitations: Women for these studies were not selected by menopausal status. The study designs were intended to simulate exaggerated conditions of transfer.