A clinical trial of 7α-methyl-19-nortestosterone implants for possible use as a long-acting contraceptive for men
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,
von Eckardstein, Sigrid, Gabriela Noe, Vivian Brache, Eberhard Nieschlag, Horacio B. Croxatto, Francisco Alvarez-Sanchez, Alfred J. Moo-Young, Irving Sivin, Narender Kumar, Margaret Small, and Kalyan Sundaram. 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.