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

Abstract

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.

Figure 1

Serum LH (A) and FSH (B) concentrations before and after transdermal application of NES and T gel for 20 d. The dotted line represents the lower limit of quantification of serum LH and FSH, respectively. Box and whiskers plots are used in all figures where the dark line in the box is the median and the dotted line is the mean concentration. The lower and upper box boundaries represent the 25th and 75th percentiles, the whiskers are the 10th and 90th percentiles, and the dots are values below the 10th or above the 90th percentiles.

Figure 2

Serum NES levels in the subjects administering NES gel for 20 d.

Figure 3

Serum total T (A), free T (B), and SHBG (C) concentrations before and after transdermal application of NES and T gel for 20 d.