Suppression of spermatogenesis by etonogestrel implants with depot testosterone: Potential for long-acting male contraception

The coadministration of a progestogen with testosterone increases the degree of suppression of spermatogenesis and is one approach to the development of hormonal male contraception. Depot formulations may allow a reduction in dosage, minimizing adverse effects. We have investigated the effects of a sc implant containing the progestogen etonogestrel (Implanon) with depot testosterone on spermatogenesis in normal men. Twenty-eight men were randomized to receive either one or two etonogestrel implants, removed after 24 wk. All men additionally received 400 mg testosterone pellets on d 1 and at 12 wk. Four men withdrew during the study, three because of side effects. Testosterone concentrations remained within the physiological range during treatment, although they were overall slightly reduced, compared with pretreatment. Both groups showed marked suppression of spermatogenesis, nine men in each group achieving azoospermia (64% and 75% in the one- and two-implant groups, respectively). Sperm concentrations in 13/14 men in the two-implant group fell to 0.1 X 10(6)/ml or less. Spermatogenic suppression was more variable in the one-implant group, with partial recovery in three men. Incomplete suppression of spermatogenesis in the one-implant group was associated with less complete suppression of gonadotropins. There were no significant changes in body weight, hemoglobin, hematocrit, or high-density lipoprotein cholesterol concentrations during treatment. These data demonstrate that etonogestrel implants with depot testosterone provide effective suppression of spermatogenesis with reduced metabolic effects and are, therefore, a promising approach to the development of long-acting yet reversible male contraception.