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

Author(s): Mahabadi V, Amory JK, Swerdloff RS, Bremner WJ, Page ST, Sitruk-Ware R, Christensen PD, Kumar N, Tsong YY, Blithe D, Wang C

Affiliation(s): Department of Medicine, Division of Endocrinology, Harbor-UCLA Medical Center and Los Angeles Biomedical Research Institute, Torrance, California 90509, USA.

Publication date & source: 2009-07, J Clin Endocrinol Metab., 94(7):2313-20. Epub 2009 Apr 14.

Publication type: Multicenter Study; Randomized Controlled Trial; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, P.H.S.

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.