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.
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.
A total of 140 healthy male volunteers participated.
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.
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.
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.