A Clinical Trial of 7α-Methyl-19-Nortestosterone Implants for Possible Use as a Long-Acting Contraceptive for Men

Sigrid Von Eckardstein, Gabriela Noe, Vivian Brache, Eberhard Nieschlag, Horacio Croxatto, Francisco Alvarez, Alfred Moo-Young, Irving Sivin, Narender Kumar, Margaret Small, Kalyan Sundaram

Resultado de la investigación: Contribución a una revistaArtículo

89 Citas (Scopus)

Resumen

Several preparations of testosterone and its esters are being investigated alone or in combination with other gonadotropin-suppressing agents as possible antifertility agents for men. We studied the effectiveness of 7α-methyl-19-nortestosterone (MENT) as an antispermatogenic agent in men. MENT has been shown to be more potent than testosterone and to be resistant to 5α-reduction. For sustained delivery of MENT, we used a system consisting of ethylene vinyl acetate implants containing MENT acetate (Ac), administered subdermally. Thirty-five normal volunteers were recruited in 3 clinics and were randomly assigned to 1 of 3 doses: 1 (12 men), 2 (11 men), or 4 (12 men) MENT Ac implants. The initial average in vitro release rate of MENT Ac from each implant was approximately 400 μg/day. Implants were inserted subdermally in the medial aspect of the upper arm under local anesthesia. The duration of treatment was initially designed to be 6 months. However, in 2 clinics the duration of treatment was extended to 9 months for the 2-implant group and to 12 months for the 4-implant group. Dose-related increases in serum MENT levels and decreases in testosterone, LH, and FSH levels were observed. Effects on sperm counts were also dose related. None of the subjects in the 1-implant group exhibited oligozoospermia (sperm count, <3 million/ml). Four subjects in the 2-implant group became oligozoospermic, 2 of whom reached azoospermia. Eight subjects in the 4-implant group reached azoospermia, with 1 exhibiting oligozoospermia, whereas 2 were nonresponders. Side effects generally seen with androgen administration, such as increases in erythrocyte count, hematocrit, and hemoglobin and a decrease in SHBG, were also seen in this study and were reversible. Changes in lipid parameters were moderate and transient. Liver enzymes showed small changes. This study demonstrates that MENT Ac, when administered in a sustained release fashion via subdermal implants, can inhibit spermatogenesis over a prolonged period after a single administration and has the potential to be used as a male contraceptive.

Idioma originalInglés
Páginas (desde-hasta)5232-5239
Número de páginas8
PublicaciónJournal of Clinical Endocrinology and Metabolism
Volumen88
N.º11
DOI
EstadoPublicada - nov 2003

Áreas temáticas de ASJC Scopus

  • Endocrinología, diabetes y metabolismo
  • Bioquímica
  • Endocrinología
  • Bioquímica clínica
  • Bioquímica médica

Huella Profundice en los temas de investigación de 'A Clinical Trial of 7α-Methyl-19-Nortestosterone Implants for Possible Use as a Long-Acting Contraceptive for Men'. En conjunto forman una huella única.

  • Citar esto

    Von Eckardstein, S., Noe, G., Brache, V., Nieschlag, E., Croxatto, H., Alvarez, F., Moo-Young, A., Sivin, I., Kumar, N., Small, M., & Sundaram, K. (2003). A Clinical Trial of 7α-Methyl-19-Nortestosterone Implants for Possible Use as a Long-Acting Contraceptive for Men. Journal of Clinical Endocrinology and Metabolism, 88(11), 5232-5239. https://doi.org/10.1210/jc.2002-022043