LONG-TERM SEQUELAE OF TOLNIDAMINE ON MALE REPRODUCTION AND GENERAL BODY METABOLISM IN RABBITS

The long-term effects of tolnidamine on male reproduction and general body metabolism were studied in rabbits (Oryctolagus cuniculus). The s tudy was divided into three groups of 10 animals each. The first group (A) received vehicle alone to serve as controls. The second and third groups (B and C) of animals were administered tolnidamine orally at 5 0 mg/kg body weight/week and 50 mg/kg body weight/day, respectively, f or a period of 150 days. The animals of group B exhibited a sperm dens ity of 23.60 million/mL +/- 4.87 million/mL (vs 453.00 million/mL +/- 65.30 million/mL in group A) after 150 days of treatment. In group C, all animals were azoospermic after 135 days of treatment. A reversible impairment of sperm motility, vitality and morphology was noticed. Se men weight, volume, color, pH, libido, and circulatory levels of testo sterone remained unchanged. In group B animals, sperm density did not return to control levels even at 150 days after cessation of treatment (37.40 million/mL +/- 4.46 million/mL, vs 380.00 +/- 40.80 million/mL in group A). However, spermatozoa reappeared in animals treated daily (group C) after 30 days of recovery but remained <5 million/mL during the entire recovery period. A reversible, significant depletion was r ecorded in seminal glycerylphosphorylcholine (GPC) levels. Fertility w as unimpaired in group B animals when compared with those in group A. In group C, fertility was reduced to zero after 150 days of treatment and at 90 days and 150 days after cessation of treatment. No significa nt alterations were observed in other semen biochemical, hematologic, or blood/serum biochemical parameters with either dose regimen. It is concluded that tolnidamine administration induced dose dependent, irre versible inhibition of sperm production without altering general body metabolism in male rabbits. CONTRACEPTION 1998;57:271-279 (C) 1998 Els evier Science Inc. All rights reserved.