Context: Testosterone (T) plus progestin combinations are the most promising hormonal male contraceptives. Nestorone (NES), a progestin without estrogenic or androgenic activity, when combined with T may be an excellent candidate for male contraception.
Objective: Our objective was to determine the effect of transdermal NES gel alone or with T gel on gonadotropin suppression.
Design and setting: The randomized, unblinded clinical trial was 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 T gel 10 g plus NES gel 2 or 4 mg daily for 20 d. Because only about half of the subjects in T plus NES 4 mg group suppressed serum gonadotropins to 0.5 IU/liter or less (suboptimal suppression), two additional groups of 20 men were randomized to apply daily T gel 10 g plus NES gel 6 or 8 mg.
Main outcome variable: Suppression of serum LH and FSH concentrations to 0.5 IU/liter or less after treatment was the main outcome variable.
Results: A total of 119 subjects were compliant with gel applications with few study-related adverse events. NES alone reduced gonadotropins significantly but less than T gel alone. Combined T gel 10g plus NES gel 6 or 8 mg suppressed both serum gonadotropins to 0.5 IU/liter or less in significantly more men than either gel alone.
Conclusion: Transdermal NES gel alone had gonadotropin suppression activity. Combined transdermal NES (6 or 8 mg) plus T gel demonstrated safe and effective suppression of gonadotropins, justifying a longer-term study of this combination for suppression of spermatogenesis.