A new combination of testosterone and nestorone transdermal gels for male hormonal contraception

Abstract

Context: Combinations of testosterone (T) and nestorone (NES; a nonandrogenic progestin) transdermal gels may suppress spermatogenesis and prove appealing to men for contraception.

Objective: The objective of the study was to determine the effectiveness of T gel alone or combined with NES gel in suppressing spermatogenesis.

Design and setting: This was a randomized, double-blind, comparator clinical trial conducted at two academic medical centers.

Participants: Ninety-nine healthy male volunteers participated in the study.

Interventions: Volunteers were randomized to one of three treatment groups applying daily transdermal gels (group 1: T gel 10 g+NES 0 mg/placebo gel; group 2: T gel 10 g+NES gel 8 mg; group 3: T gel 10 g+NES gel 12 mg).

Main outcome variable: The main outcome variable of the study was the percentage of men whose sperm concentration was suppressed to 1 million/ml or less by 20-24 wk of treatment.

Results: Efficacy data analyses were performed on 56 subjects who adhered to the protocol and completed at least 20 wk of treatment. The percentage of men whose sperm concentration was 1 million/ml or less was significantly higher for T+NES 8 mg (89%, P<0.0001) and T+NES 12 mg (88%, P=0.0002) compared with T+NES 0 mg group (23%). The median serum total and free T concentrations in all groups were maintained within the adult male range throughout the treatment period. Adverse effects were minimal in all groups.

Conclusion: A combination of daily NES+T gels suppressed sperm concentration to 1 million/ml or less in 88.5% of men, with minimal adverse effects, and may be further studied as a male transdermal hormonal contraceptive.

Fig. 1.

Subject enrollment, randomization, and disposition. BMI, Body mass index; BP, blood pressure.

Fig. 2.

Percent of subjects with sperm concentration suppressed to 0, 1 million or less, 3 million or less, and more than 3 million/ml in the three treatment groups: T + NES 0 mg (A), T + NES 8 mg (B), and T + NES 12 mg group (C) during the treatment and recovery periods.

Fig. 3.

Sperm concentration (A), semen volume (B), total sperm count per ejaculate (C), percentage motility (D), and percentage normal morphology (E) (median, 25th, and 75th percentile) in each treatment group during each assessment week in the pretreatment (PRE), treatment, and recovery periods. Note that a fourth root transformation was used for the sperm concentration (A) and the fifth root for total sperm count per ejaculate (C). Sperm motility and morphology were assessed only in samples with more than 5000 spermatozoa/ml. Dotted lines represent the lower reference range in adult men.

Fig. 4.

Serum T (A), free T (B), NES (C), SHBG (D), LH (E), and FSH (F) concentrations (median, 25th, and 75th percentiles) in each treatment group during each assessment week in the pretreatment (PRE), treatment, and recovery period. Dotted lines represent the reference range in adult men.

Fig. 5.

Psychosexual diary scores (median, 25th, and 75th percentiles) for each treatment group at wk 0 (baseline), 12 and 24 wk (treatment), and 36 wk (recovery). A, Sexual activity; B, sexual desire; C, sexual enjoyment with partner; D, sexual enjoyment without partner; E, positive mood; and F, negative mood scores.