A clinical trial of 7α-methyl-19-nortestosterone implants for possible use as a long-acting contraceptive for men
von Eckardstein,Sigrid; Noe,Gabriela; Brache,Vivian; Nieschlag,Eberhard; Croxatto,Horacio B.; Alvarez-Sanchez,Francisco; Moo-Young,Alfred J.; Sivin,Irving; Kumar,Narender; Small,Margaret; Sundaram,Kalyan; Population Council International Committee for Contraception Research
Journal of Clinical Endocrinology and Metabolism 88(11): 5232-5239
Publication date: 2003
Several preparations of testosterone and its esters are beinginvestigated alone or in combination with other gonadotropin-suppressingagents as possible antifertility agents for men. We studiedthe effectiveness of 7-methyl-19-nortestosterone (MENT) as anantispermatogenic agent in men. MENT has been shown to be morepotent than testosterone and to be resistant to 5-reduction.For sustained delivery of MENT, we used a system consistingof ethylene vinyl acetate implants containing MENT acetate (Ac),administered subdermally. Thirty-five normal volunteers wererecruited in 3 clinics and were randomly assigned to 1 of 3doses: 1 (12 men), 2 (11 men), or 4 (12 men) MENT Ac implants.The initial average in vitro release rate of MENT Ac from eachimplant was approximately 400 µg/day. Implants were insertedsubdermally in the medial aspect of the upper arm under localanesthesia. The duration of treatment was initially designedto be 6 months. However, in 2 clinics the duration of treatmentwas extended to 9 months for the 2-implant group and to 12 monthsfor the 4-implant group. Dose-related increases in serum MENTlevels and decreases in testosterone, LH, and FSH levels wereobserved. Effects on sperm counts were also dose related. Noneof the subjects in the 1-implant group exhibited oligozoospermia(sperm count, <3 million/ml). Four subjects in the 2-implantgroup became oligozoospermic, 2 of whom reached azoospermia.Eight subjects in the 4-implant group reached azoospermia, with1 exhibiting oligozoospermia, whereas 2 were nonresponders.Side effects generally seen with androgen administration, suchas increases in erythrocyte count, hematocrit, and hemoglobinand a decrease in SHBG, were also seen in this study and werereversible. Changes in lipid parameters were moderate and transient.Liver enzymes showed small changes. This study demonstratesthat MENT Ac, when administered in a sustained release fashionvia subdermal implants, can inhibit spermatogenesis over a prolongedperiod after a single administration and has the potential tobe used as a male contraceptive.