Combined Nestorone–testosterone gel suppresses serum gonadotropins to concentrations associated with effective hormonal contraception in men

Authors

Bradley D. Anawalt
Mara Y. Roth
Jonas Ceponis
Vijaya Surampadi
John K. Amory
Ronald S. Swerdloff
Peter Y. Liu
Clint Dart
William J. Bremner
Régine Sitruk-Ware, Population Council
Narender Kumar, Population Council
Diana Blithe
Stephanie T. Page
Christina Wang

Document Type

Article (peer-reviewed)

Publication Date

2019

Abstract

Background: Novel male‐based contraceptives are needed to broaden family planning choices. A progestin, Nestorone® (Nes) gel, plus a testosterone (T) gel suppresses sperm concentrations to levels associated with effective contraception in normal men. However, administration of two gels on different parts of the body daily is impractical. Objective: Compare the effectiveness of daily application of a single, combined 8.3 mg Nes‐62.5 mg T gel (Nes‐T) vs. 62.7 mg T gel to suppress serum FSH and LH concentrations to ≤1.0 IU/L (a threshold associated with suppression of sperm concentrations to ≤1 million and effective contraception) and to compare the pharmacokinetics of serum Nes and T concentrations between the gel groups. Design: We conducted a 28‐day, double‐blind, controlled trial of 44 healthy men randomized to daily Nes‐T or T gel with measurement of hormones at baseline, treatment, and recovery and during 24‐h pharmacokinetic studies on days 1 and 28 of treatment. Results: Of the subjects who met pre‐defined inclusion criteria, 84% of the Nes‐T group suppressed serum gonadotropin concentrations to ≤ 1.0 IU/L at days 21–28 vs. 16.7% in the T group (p < 0.001). On day 1, Nes concentrations rose significantly above baseline by 2 h and continued to rise up to 24 h after Nes‐T gel application. Nes concentrations were not detectable in the T group. Serum total T concentrations rose and were significantly higher in the T gel group compared to the Nes‐T group at 24 h on day 1 and days 11, 14, and 21 (p < 0.01). There were no serious adverse events in either group. About 80% of the subjects reported satisfaction with both gels. Conclusion: Daily Nes‐T gel effectively and safely suppresses serum gonadotropins and is acceptable to most men. It should be studied further in efficacy trials of hormonal male contraception.

Recommended Citation

Anawalt, Bradley D., Mara Y. Roth, Jonas Ceponis, Vijaya Surampadi, John K. Amory, Ronald S. Swerdloff, Peter Y. Liu, Clint Dart, William J. Bremner, Régine Sitruk-Ware, Narender Kumar, Diana Blithe, Stephanie T. Page, and Christina Wang. 2019. "Combined Nestorone–testosterone gel suppresses serum gonadotropins to concentrations associated with effective hormonal contraception in men," Andrology, https://doi.org/10.1111/andr.12603.

DOI

10.1111/andr.12603

Language

English

Project

Nestorone®/Testosterone Transdermal Gel for Male Contraception