Preventing secondary exposure to women from men applying a novel nestorone/testosterone contraceptive gel

Abstract

Background: Testosterone (T)/Nestorone (NES) combination gel is a potential transdermal male contraceptive that suppresses gonadotropins and spermatogenesis. Transfer of transdermal T from men to women can be prevented by washing or covering application sites with clothing.

Objectives: We hypothesized that showering or wearing a shirt over gel application sites would prevent secondary exposure of T and NES to a woman after close skin contact.

Materials and methods: Twelve healthy male and 12 healthy female participants were recruited. Men applied T/NES 62 mg/8 mg gel to their shoulders and upper arms. Two hours after application, female partners rubbed the application site for 15 min. Exposure in the female partner was assessed under three conditions: a shirt covered the application site; the man showered prior to skin contact; or without intervention to reduce transfer. Serum T and NES concentrations were measured by LC-MS/MS in serial blood samples for 24 h after gel exposure.

Main outcomes: Change in female serum T and NES levels as measured by average concentration over 24 h (Cavg ).

Results: Median female serum T Cavg was 23.9 ng/dL (interquartile range, 19.3, 33.9) with the shirt barrier and 26.7 ng/dL (20.7, 33.9) after showering, which was higher than baseline 20.9 ng/dL (16.7, 25.0), both p < 0.03) but lower than without intervention (58.2 ng/dL [30.9, 89.1], both p < 0.01). Female serum NES Cavg and maximum concentration were below the lower limit of quantification with the shirt barrier and after showering, but increased without intervention in six of 12 women (maximum concentration <60 pg/mL). Men had lower average serum NES levels after showering (47 pg/ml [20, 94] compared to no intervention (153.3 pg/mL [51, 241], p < 0.02).

Conclusion: Secondary transfer of T and NES occurs after intensive skin contact with the gel application site. Secondary transfer is decreased by a shirt barrier or showering before contact.

Trial registration: ClinicalTrials.gov NCT02994602.

Keywords: androgen; male contraceptive; nestorone; progestin; skin transfer; transdermal gels.

© 2018 American Society of Andrology and European Academy of Andrology.

Figures

Fig. 1.

A. Serum testosterone (T) concentrations over 24 hours in female participants after secondary exposure to T/NES gel (left panel) and in male participants after T/NES gel application (right panels). Mean ± 95% confidence intervals are displayed. Dotted lines show the normal reference range of T in women and men. B. Average serum T concentrations (Cavg) over 24 hours in female participants (left panel) and male participants (right panel). Medians (line in box), interquartile ranges (box), 5th and 95th percentile ranges (whiskers), and outliers (closed circles) are displayed.

Fig. 2.

A. Serum Nestorone (NES) concentrations over 24 hours in female participants after secondary exposure to T/NES gel (left panel) and in male participants after T/NES application (right panel). Mean±95% confidence intervals are displayed. The LLOQ of NES (10 pg/ml) is represented by the dotted line. B. Maximum serum NES concentrations (Cmax) over 24 hours in female participants (left panel) and average serum NES concentrations (Cavg) over 24 hours in male participants (right panel). Average serum NES concentrations over 24 hours (Cavg) in females were below LLOQ for all three scenarios and not shown. Medians (line in box), interquartile ranges (box), 5th and 95th percentile ranges (whiskers), and outliers (closed circles) are displayed.

Fig 3.

A. Adhesive D-squame strips were applied and stripped from the gel application site at 1.5 h and 2.5 h after T/NES gel application. The left panel shows T concentrations on the skin per participant before and after shower and skin contact. The right panel shows T concentrations on the skin before and after skin contact alone without intervention. B. The left panel shows NES concentrations on the skin before and after shower and skin contact; the right panel shows NES concentrations on the skin before and after skin contact alone with no intervention. Medians (line in box), interquartile ranges (box), 5th and 95th percentile ranges (whiskers), and outliers (closed circles) are displayed. T/NES was applied at 0h, the male participant showered at 1.75h (1 h 45 min), and skin contact occurred at 2h in the shower scenario. T/NES was applied at 0 h and skin contact occurred at 2h in the no intervention scenario.