Pharmacokinetics of Testosterone Undecanoate Injected Alone or in Combination With Norethisterone Enanthate in Healthy Men

Authors

  • Ammar Qoubaitary,

    1. Division of Endocrinology, Department of Medicine, Harbor-UCLA Medical Center and Los Angeles Biomedical Research Institute, Torrance, California
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  • Cristina Meriggiola,

    1. Department of Obstetrics and Gynecology, University of Bologna, Bologna, Italy
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  • Chiu Ming Ng,

    1. Division of Endocrinology, Department of Medicine, Harbor-UCLA Medical Center and Los Angeles Biomedical Research Institute, Torrance, California
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  • Leslie Lumbreras,

    1. Division of Endocrinology, Department of Medicine, Harbor-UCLA Medical Center and Los Angeles Biomedical Research Institute, Torrance, California
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  • Silvia Cerpolini,

    1. Department of Obstetrics and Gynecology, University of Bologna, Bologna, Italy
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  • G. Pelusi,

    1. Department of Obstetrics and Gynecology, University of Bologna, Bologna, Italy
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  • Peter D. Christensen,

    1. Division of Endocrinology, Department of Medicine, Harbor-UCLA Medical Center and Los Angeles Biomedical Research Institute, Torrance, California
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  • Laura Hull,

    1. Division of Endocrinology, Department of Medicine, Harbor-UCLA Medical Center and Los Angeles Biomedical Research Institute, Torrance, California
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  • Ronald S. Swerdloff,

    1. Division of Endocrinology, Department of Medicine, Harbor-UCLA Medical Center and Los Angeles Biomedical Research Institute, Torrance, California
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  • Christina Wang

    Corresponding author
    1. Division of Endocrinology, Department of Medicine, Harbor-UCLA Medical Center and Los Angeles Biomedical Research Institute, Torrance, California
      Dr Christina Wang, General Clinical Research Center, Box 16, Harbor-UCLA Medical Center, 1000 West Carson Street, Torrance, CA 90509 (e-mail: Wang@labiomed.org.edu).
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  • Presented in part at ENDO 2005, San Diego, June 2005.

  • Supported by the Contraceptive Research and Development Program (CIG-03–94, CIG-04–99), the GCRC at Harbor-UCLA Medical Center (MO1 RR00425), and the Endocrinology and Metabolism Training grant (T32 DK007571).

Dr Christina Wang, General Clinical Research Center, Box 16, Harbor-UCLA Medical Center, 1000 West Carson Street, Torrance, CA 90509 (e-mail: Wang@labiomed.org.edu).

Abstract

ABSTRACT: 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.

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