Pharmacokinetics of testosterone undecanoate injected alone or in combination with norethisterone enanthate in healthy men.

Long-acting injectable testosterone undecanoate (TU) is a promising androgen for male hormonal contraception. As a prerequisite for a planned multicenter male contraceptive efficacy study, we studied the pharmacokinetics of 2 doses of TU alone or in combination with norethisterone enanthate (NETE) in a prospective 2-center study, randomized for TU dose in each center. Twenty healthy male volunteers in each center were administered intramuscular injections of 750 or 1000 mg TU alone or in combination with 200 mg of NETE IM every 8 weeks for 3 injections. There were no significant differences in maximum concentration and area under the curve (AUC) for serum total and free testosterone (T) between the TU 750 and 1000 mg groups, irrespective of whether TU was administered with 200 mg of NETE. TU 1000 mg IM alone or with NETE at 8-weekly intervals resulted in linear increases in average concentration and AUC of serum total and free T with each injection. Accumulation ratios of serum total and free T levels (calculated as 8 weeks post- to preinjection levels) for each period showed significant increases in the TU+ NETE groups. Serum gonadotropins levels and sperm concentration were more consistently suppressed in the TU 1000 mg + NETE group. We conclude that despite some accumulation of T, TU 1000 mg + NETE 200 mg administered every 8 weeks may be preferable for the future contraceptive efficacy study because of more complete suppression of gonadotropins and spermatogenesis.

Levonorgestrel implants enhanced the suppression of spermatogenesis by testosterone implants: comparison between Chinese and non-Chinese men.

CONTEXT: Previous male contraceptive studies showed that progestins enhance spermatogenesis suppression by androgens in men. OBJECTIVE: We compared the efficacy of spermatogenesis suppression by the combination of levonorgestrel (LNG) with testosterone (T) implants to that by T implants alone in two different ethnic groups. DESIGN: This was a randomized trial performed in two centers with two treatment groups. SETTINGS: The study was performed at the Academic Medical Center in the United States and the Research Institute in China. PARTICIPANTS: Forty non-Chinese and 40 Chinese healthy male volunteers were studied. INTERVENTIONS: Subjects were randomized to receive four LNG implants together with four T implants (inserted on d 1 and wk 15-18) vs. T implants alone for 30 wk. MAIN OUTCOME MEASURES: The primary end point compared the efficiency of suppression to severe oligozoospermia (1 x 10(6)/ml) by LNG plus T implants vs. that by T implants alone. The secondary end point examined differences in spermatogenesis suppression between Chinese and non-Chinese subjects. RESULTS: LNG plus T implants caused more suppression of spermatogenesis to severe oligozoospermia during the treatment period than T implants alone at both sites (P < 0.02). In Chinese men, severe oligozoospermia was achieved in more than 90% of the men in both treatment groups. Suppression to severe oligozoospermia was less in the non-Chinese men (59%) after T alone (P < 0.020); this difference disappeared with combined treatment (89%). T implant extrusion occurred in six men. Acne and increased hemoglobin were the most common adverse events. CONCLUSION: T implants resulted in more pronounced spermatogenesis suppression in Chinese men. Addition of LNG implants to T implants enhanced the suppression of spermatogenesis in the treatment period in both Chinese and non-Chinese men.