Levonorgestrel Implants (Norplant II) for Male Contraception Clinical Trials: Combination with Transdermal and Injectable Testosterone

• Published in: The journal of clinical endocrinology and metabolism 2002-08, Vol.87 (8), p.3562-3572
• Main Authors: Gonzalo, I. T. Gaw, Swerdloff, R. S., Nelson, A. L., Clevenger, B., Garcia, R., Berman, N., Wang, C.
• Format: Article
• Language: English
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jcem.87.8.8710

Recent studies demonstrate that combinations of androgens and progestagens are highly effective in the suppression of spermatogenesis in normal volunteers. To test whether progestagen and androgen delivery systems designed to produce steady serum levels will be as effective as other androgen plus progestagen combinations, we compared Norplant II and testosterone (T) transdermal patch to T patch alone on the suppression of spermatogenesis in normal men. Thirty-nine healthy male volunteers (age, 20–45 yr) were randomly assigned to one of two groups. Group 1 (n = 19) received two transdermal T patches daily (Testoderm TTS, each patch designed to deliver about 5 mg/d T) alone, and group 2 (n = 20) received combined Norplant II [Jadelle, four capsules delivering ∼160 μg/d levonorgestrel (LNG)] plus T patch. Neither of these regimens were very effective, with suppression of spermatogenesis to severe oligozoospermia occurring in less than 60% of subjects. We then expanded the study to include two more groups to determine whether T patch or Norplant II was the main factor causing the inadequate suppression of spermatogenesis. Another 29 subjects were randomized to one of two groups. Group 3 (n = 15) received oral LNG (125 μg/d) plus T patch, and group 4 (n = 14) received Norplant II plus T enanthate (TE) injection (100 mg/wk im). After a pretreatment phase of 4 wk, all subjects received treatment for 24 wk, followed by a recovery period of 12–24 wk. Steady-state serum LNG levels (800–1200 pmol/liter) were achieved from wk 3–24 after Norplant II insertion and decreased rapidly after the removal of the implants at wk 24. Trough serum LNG levels after oral LNG administration were at a comparable range (940–1300 pmol/liter). Azoospermia was achieved in 24%, 35%, 33%, and 93%, and severe oligozoospermia (