A new combination of testosterone and nestorone transdermal gels for male hormonal contraception

J Clin Endocrinol Metab. 2012 Oct;97(10):3476-86. doi: 10.1210/jc.2012-1384. Epub 2012 Jul 12.


Context: Combinations of testosterone (T) and nestorone (NES; a nonandrogenic progestin) transdermal gels may suppress spermatogenesis and prove appealing to men for contraception.

Objective: The objective of the study was to determine the effectiveness of T gel alone or combined with NES gel in suppressing spermatogenesis.

Design and setting: This was a randomized, double-blind, comparator clinical trial conducted at two academic medical centers.

Participants: Ninety-nine healthy male volunteers participated in the study.

Interventions: Volunteers were randomized to one of three treatment groups applying daily transdermal gels (group 1: T gel 10 g+NES 0 mg/placebo gel; group 2: T gel 10 g+NES gel 8 mg; group 3: T gel 10 g+NES gel 12 mg).

Main outcome variable: The main outcome variable of the study was the percentage of men whose sperm concentration was suppressed to 1 million/ml or less by 20-24 wk of treatment.

Results: Efficacy data analyses were performed on 56 subjects who adhered to the protocol and completed at least 20 wk of treatment. The percentage of men whose sperm concentration was 1 million/ml or less was significantly higher for T+NES 8 mg (89%, P<0.0001) and T+NES 12 mg (88%, P=0.0002) compared with T+NES 0 mg group (23%). The median serum total and free T concentrations in all groups were maintained within the adult male range throughout the treatment period. Adverse effects were minimal in all groups.

Conclusion: A combination of daily NES+T gels suppressed sperm concentration to 1 million/ml or less in 88.5% of men, with minimal adverse effects, and may be further studied as a male transdermal hormonal contraceptive.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Cutaneous
  • Adolescent
  • Adult
  • Androgens / administration & dosage
  • Androgens / adverse effects
  • Androgens / blood
  • Contraception / methods*
  • Contraceptive Agents, Female / administration & dosage
  • Contraceptive Agents, Female / adverse effects
  • Drug Combinations
  • Gels / administration & dosage
  • Humans
  • Male
  • Middle Aged
  • Norprogesterones / administration & dosage*
  • Norprogesterones / adverse effects
  • Patient Satisfaction
  • Sexuality / drug effects
  • Spermatogenesis / drug effects*
  • Testosterone / administration & dosage*
  • Testosterone / adverse effects
  • Testosterone / blood
  • Young Adult


  • Androgens
  • Contraceptive Agents, Female
  • Drug Combinations
  • Gels
  • Norprogesterones
  • Testosterone
  • ST 1435