Journal Article

Combined transdermal testosterone gel and the progestin Nestorone suppresses serum gonadotropins in men

Context
Testosterone (T) plus progestin combinations are themost promising hormonal male contraceptives. Nestorone (NES),a progestin without estrogenic or androgenic activity, whencombined with T may be an excellent candidate for male contraception.

Objective
Our objective was to determine the effect of transdermalNES gel alone or with T gel on gonadotropin suppression.

Design and Setting
The randomized, unblinded clinical trialwas conducted at two academic medical centers.

Participants
A total of 140 healthy male volunteers participated.

Interventions
One hundred subjects were randomized initially(20 per group) to apply NES gel 2 or 4 mg, T gel 10 g, or Tgel 10 g plus NES gel 2 or 4 mg daily for 20 d. Because onlyabout half of the subjects in T plus NES 4 mg group suppressedserum gonadotropins to 0.5 IU/liter or less (suboptimal suppression),two additional groups of 20 men were randomized to apply dailyT gel 10 g plus NES gel 6 or 8 mg.

Main Outcome Variable
Suppression of serum LH and FSH concentrationsto 0.5 IU/liter or less after treatment was the main outcomevariable.

Results
A total of 119 subjects were compliant with gel applicationswith few study-related adverse events. NES alone reduced gonadotropinssignificantly but less than T gel alone. Combined T gel 10gplus NES gel 6 or 8 mg suppressed both serum gonadotropins to0.5 IU/liter or less in significantly more men than either gelalone.

Conclusion
Transdermal NES gel alone had gonadotropin suppressionactivity. Combined transdermal NES (6 or 8 mg) plus T gel demonstratedsafe and effective suppression of gonadotropins, justifying

a longer-term study of this combination for suppression of spermatogenesis.