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 (C avg ). Results: Median female serum T C avg 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 C avg 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.

Simultaneous assay of segesterone acetate (Nestorone®), estradiol, progesterone, and estrone in human serum by LC–MS/MS

“…In this report, we describe a method for the simultaneous assay of the synthetic progestin NES and three endogenous steroid hormones, E2, P4, and E1, by LC-MS/MS. While reports of hormonal contraceptive and endogenous steroid analysis by LC-MS/MS are abundant, there are limited reports of an assay for NES [10,14]. The method described here is the first to include simultaneous analysis of endogenous steroid hormones and NES.…”

“…Because NES effectively blocks follicle development and ovarian production of E2, the ability to measure concentrations of both NES and E2 is critical to evaluate the efficacy of this new CVR. There are currently limited methods available to quantify NES in human serum, and these methods require a dedicated aliquot for the measurement of NES [10,14]. A previous study similar to the study described herein required the measurement of both NES and E2 in study samples; due to limitations at the respective testing laboratories, separate laboratories were required for analysis of NES and E2 [10].…”

Contraception au futur

“…Cette dose quotidienne bloque les gonadotrophines et induit une azoospermie [41]. Le transfert du gel entre partenaires doit cependant être évité [42]. Les précautions requises pour éviter ce transfert sont bien acceptées par les couples inclus dans l'étude clinique et les résultats préliminaires sont fort encourageants tant en matière d'efficacité que de sécurité et d'acceptabilité.…”

Continuing the search for a hormonal male contraceptive

“…The development of the testosterone/nestorone combined gel included: (1) A dose finding, first-in-man study of nestorone in men [59], (2) A six-month study showing that the selected nestorone dose with a standard dose of testosterone used for testosterone replacement in hypogonadal men effectively suppressed spermatogenesis [29], (3) A pharmacokinetics study of the combined gel [60], and (4) A study to determine transfer of the hormones to the female partner under an experimental paradigm [61]. Following these studies, a Phase IIb trial of a self-applied, nestorone/testosterone combination transdermal gel started at the end of 2018 (NCT03452111).…”